The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: GSK2231392A (GlaxoSmithKline [GSK] Biologicals investigational adjuvanted vaccine against Hepatitis B) Study Number: 116640 (EARLY-CLINRES-008) Title: Development of read-outs to detect and characterise the early and adaptive immune responses in healthy, hepatitis B virus naive adults vaccinated with the hepatitis B surface antigen in combination with a GSK Biologicals Adjuvant System. Rationale: The main purpose of this clinical trial is to develop new read-outs aimed at detecting and characterising the early immune response and its kinetics within the first days after vaccination as well as the adaptive immune response to the hepatitis B surface antigen (used as model antigen) in combination with a GSK Biologicals Adjuvant System or with aluminium hydroxide (Engerix -B). The immunogenicity and safety of the two vaccine formulations are to be evaluated up to 6 months post last study vaccine administration: HBsAg/AS - GSK Biologicals investigational adjuvanted Hepatitis B formulation Engerix -B (HBsAg/Alum) - GSK Biologicals Hepatitis B vaccine adjuvanted with aluminium hydroxide. Phase: II Study Period: From 25-Feb-13 to 05-Aug-2014 (end of Step 1) 13-Sept-2016 (end of Step 2) Study Design: Randomised, single-blind (in Step 1) and open-label (in Step 2), single centre controlled study in 2 Steps. The duration of the study for each subject enrolled in Step 1 was approximately 240 days from placebo administration. In Step 2, the duration of the study for each subject enrolled in the group receiving HBsAg/AS was approximately 180 days from Dose 1 administration and approximately 330 days from Dose 1 administration for each subject enrolled in the group receiving HBsAg/Alum. Centres: 1 Centre in Belgium. Indication: Hepatitis B surface antigen (HBsAg) vaccine administered in hepatitis B virus (HBV) naive adult subjects aged between 18 and 45 years old, inclusive, in good general health. Treatment: In Step 1, the study groups were as follows: -S1AS Group: ~30 subjects aged 18-45 years, who received 1 dose of Placebo at Day -30 followed by 2 doses of HBsAg/AS, at Day 0 and Day 30 -S1Alum Group: ~30 subjects aged 18-45 years, who received 1 dose of Placebo at Day -30 followed by 3 doses of HBsAg/Alum at Day 0, Day 30 and Day 180. In this step, a sub-cohort of ~30 subjects (~15 in each group) was asked to stay overnight at the study centre to allow collection of blood for the evaluation of immunogenicity and to evaluate reactogenicity and safety 18 hours post study product administration. In Step 2, the study groups were as follows: -S2AS Group: ~15 subjects aged 18-45 years, receiving 2 doses of HBsAg/AS, at Day 0 and Day 30 -S2Alum Group: ~15 subjects aged 18-45 years, receiving 3 doses of HBsAg/Alum at Day 0, Day 30 and Day 180. Placebo and vaccines were administered intramuscularly into the deltoid muscle of the non-dominant upper arm. Note: For each parameter analysed in both Step 1 and Step 2, subjects were pooled into S1AS+S2AS Group and S1Alum+ S2Alum Group. Pooling steps also occurred for safety analyses. Objectives: To detect and measure soluble mediators from the early immune response in plasma. Primary Outcome/Efficacy Variable: Innate/early immune response: Soluble mediators from the innate/early immune response at protocol-defined time-points in all subjects (Step 1 and Step 2): Cytokines and chemokines in plasma: Concentration of cytokines and chemokines (e.g. Interleukin (IL)-6, Interferon Gamma (IFN)-γ, Macrophage Inflammatory Protein (MIP-1α), IL-8), as measured by Multiplex. Secondary Outcome/Efficacy Variable(s): Adaptive response: Classical cellular and humoral immune response to components of the study vaccine at protocol-defined time-points:
Anti-HBs IgG antibody concentrations in serum, as measured by Chemi Luminescence Immuno Assay (CLIA) (Step 1 and Step 2). Frequency of HBs-specific Cluster of Differentiation (CD)4+/CD8+ T-cells expressing at least 2 immune markers among IL-2, IFN-γ, Tumor Necrosis Factor (TNF)-α, CD40L, as measured by classical (qualified assay) Intracellular Cytokine Staining (ICS), using frozen Peripheral blood mononuclear cells (PBMCs) (Step 1 only). Occurrence of solicited and non-serious unsolicited adverse events (AEs) post first 3 study product administration in Step 1 and after each vaccine administration in Step 2: Occurrence of each solicited local and general AE as assessed by the subject during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days). Recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse up to 4 days post-placebo/vaccine administration (i.e. throughout the day of vaccination and at the 3 subsequent days) in Step 1. Recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse during a 3-day follow-up period (i.e. throughout the day of vaccination and at the 2 subsequent days) post Dose 2/Dose 3 administration in the S2AS/S2Alum groups in Step 2. Occurrence of any unsolicited AE during a 28-day follow-up period (i.e. day of vaccination and 27 subsequent days). Occurrence of any serious adverse event (SAE) occurring from first placebo/vaccine administration up to study conclusion of each step. Occurrence of any Potential Immune-Mediated Disease (pimd) occurring from first placebo/vaccine administration up to study conclusion of each step. Occurrence of any new medical condition requiring medical attention occurring from first placebo/vaccine administration up to study conclusion of each step. Safety laboratory parameters at protocol defined time-points. Haematological (Red Blood Cell (RBC), White Blood Cell (WBC) and differential count, platelets count and haemoglobin) and biochemical (Alanine aminotransferase [ALT], Aspartate aminotransferase [AST], total bilirubin, serum creatinine, urea, Lactate dehydrogenase [LDH], Creatinine phosphokinase [CPK] and c-reactive protein [CRP]) levels in Step 1. Haematological (WBC and differential count and platelets count) and biochemical (ALT, AST, total bilirubin and CRP) levels in Step 2. Vital signs at protocol defined time-points. Systolic/diastolic blood pressure. Heart rate. Respiratory rate. Statistical Methods: Analyses were performed on the Total Vaccinated cohort, the According-To-Protocol (ATP) cohort for innate immunogenicity up to Day 60, the ATP cohort for adaptive immunogenicity up to Day 60, the ATP cohort for innate immunogenicity up to 30 days post last vaccination, the ATP cohort for adaptive immunogenicity up to 30 days post last vaccination and the ATP cohort for persistence: The Total Vaccinated cohort included all subjects with at least one vaccine administration documented. The ATP cohort for innate immunogenicity up to Day 60 (step 1 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol and for whom data concerning innate immunogenicity were available for at least one innate assay at one post-vaccination time point (up to Day 60). The ATP cohort for adaptive immunogenicity up to Day 60 (step 1 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol and for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at one post-vaccination time point (up to Day 60). The ATP cohort for innate immunogenicity up to 30 days post last vaccination (step 2 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group) for whom data concerning innate immunogenicity were
available for at least one innate assay at one post-vaccination time point (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group). The ATP cohort for adaptive immunogenicity up to 30 days (step 2 only) post last vaccination included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group) for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at one post-vaccination time point (up to Day 60 for the S2AS group and up to Day 210 for the S2Alum Group). The ATP cohort for persistence (step 1 only) included all subjects from the ATP cohort for analysis of adaptive immunogenicity who complied with the procedures and intervals defined in the protocol, with no elimination criteria during the study and for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at Day 180. The ATP cohort for persistence (step 2 only) included all evaluable subjects (i.e. those who met all eligibility criteria, who received at least one dose of study vaccine according to their random assignment, who had not received a vaccine not specified or forbidden in the protocol), with no elimination criteria during the study, for whom data concerning adaptive immunogenicity were available for at least one adaptive assay at Day 180 for the S2AS Group and at Day 330 for the S2Alum Group. Analysis of Immunogenicity: For each study vaccine group in both steps, at each blood sampling time point for which results are available, descriptive statistics (N, Q1, median, Q3) of cytokine and chemokine concentrations in plasma were tabulated. For each study vaccine group in both steps, at each blood sampling time point for which anti-hbs IgG antibody concentrations are available, seropositivity rates, seroprotection rates and GMCs were tabulated with their 95% CIs. In step 1, for each study vaccine group, at each blood sampling time point for which HBs-specific CD4 + /CD8 + T-cells frequencies (by classical ICS using PBMCs) were available, descriptive statistics (N, Q1, median, Q3) were tabulated (data expressed in cells per million cells). Validated method was used, meaning that the replacement of negative and zero values was done after addition of the 11 combinations separately for the background and the HBs stimulation. The background value was then subtracted from the HBs stimulation. Analysis of Safety (solicited and unsolicited adverse events) For each study vaccine group, the following parameters were tabulated for step 1, step 2 and pooling steps: the percentage of subjects reporting each individual solicited local and general AE during the 7-day (Days 0-6) postplacebo/vaccine administration (after each dose and across doses) with exact 95% CI. The same tabulation was performed for grade 3 symptoms and for general symptoms assessed by the investigators as related to vaccination. the percentage of subjects with unsolicited AEs reported during the 28-day (Days 0-27) post-placebo/vaccine administration, as well as the summary of solicited and unsolicited AEs experienced by at least 5 % of subjects within the 28-day (Days 0-27) post-vaccination period including number of events - SAE excluded and classified according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. the percentage of subjects with pimds and the percentage of subjects with new medical condition requiring medical attention, reported from first placebo/vaccine administration up to study end. the percentage of subjects with SAEs and SAEs assessed by the investigator as related to the vaccination, reported up to study end. In addition, recording of injection site pain (using a numerical rating scale [NRS]), recording of body temperature, and measurement of injection site redness and swelling as assessed by the investigator/study nurse up to 4 days postplacebo/vaccine administration was tabulated by study vaccine group for step 1 and up to 3-days post-vaccine administration for step 2 and pooling steps (except for temperature). Descriptive statistics (N, Q1, median, Q3) of haematological and biochemical parameters and of vital signs assessed at different time points up to study end were tabulated per study vaccine group for step 1 and step 2. Study Population: Healthy male or female subjects between, and including, 18 and 45 years of age at the time of placebo (Step 1)/ first vaccine dose (Step 2) administration. Female subjects were to be of non-childbearing potential or if of childbearing potential, had to practice adequate contraception for 30 days prior to placebo (Step 1)/ first vaccine dose (Step 2) administration, to have a negative pregnancy test on the day of placebo administration/ vaccination, and were to continue such precautions during the entire treatment period and for 2 months after completion of the study. Subjects should not have any previous administration of vaccine components nor received any previous vaccination against Hepatitis B. Written informed consent was obtained from all subjects prior to enrolment in the study. Number of subjects vaccinated, completed and withdrawn with reason for withdrawal (Total Vaccinated cohort)
Step 1 S1AS Group S1Alum Group Total Group Number of subjects vaccinated 30 30 60 Number of subjects completed 27 28 55 Number of subjects withdrawn 3 2 5 Reasons for withdrawal : Serious Adverse Event 0 0 0 Non-Serious Adverse Event 0 0 0 Protocol violation 0 0 0 Consent withdrawal (not due to an adverse event) 2 1 3 Migrated/moved from study area 0 0 0 Lost to follow-up (subjects with incomplete vaccination course) 0 0 0 Lost to follow-up (subjects with complete vaccination course) 0 0 0 Sponsor study termination 0 0 0 Others 1 1 2 Step 2 S2AS Group S2Alum Group Total Group Number of subjects vaccinated 10 11 21 Number of subjects completed 10 10 20 Number of subjects withdrawn 0 1 1 Reasons for withdrawal : Serious Adverse Event 0 0 0 Non-Serious Adverse Event 0 0 0 Protocol violation 0 0 0 Consent withdrawal (not due to an adverse event) 0 1 1 Migrated/moved from study area 0 0 0 Lost to follow-up (subjects with incomplete vaccination course) 0 0 0 Lost to follow-up (subjects with complete vaccination course) 0 0 0 Sponsor study termination 0 0 0 Others 0 0 0 Pooling Steps S1AS+S2AS S1Alum+ Total Group Group S2Alum Group Number of subjects vaccinated 40 41 81 Number of subjects completed 36 38 74 Number of subjects withdrawn 4 3 7 Reasons for withdrawal : Serious Adverse Event 0 0 0 Non-Serious Adverse Event 0 0 0 Protocol violation 0 0 0 Consent withdrawal (not due to an adverse event) 2 2 4 Migrated/moved from study area 0 0 0 Lost to follow-up (subjects with incomplete vaccination course) 0 0 0 Lost to follow-up (subjects with complete vaccination course) 0 0 0 Sponsor study termination 0 0 0 Others 2 1 3 Vaccinated = number of subjects who were vaccinated in the study Completed = number of subjects who completed last study visit With Withdrawn = number of subjects who did not come back for the last visit Summary of demographic characteristics (Total Vaccinated cohort) Step 1 S1AS Group N = 30 S1Alum Group N = 30 Total Group N = 60 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean 39.0-37.2-38.1 - SD 4.2-6.5-5.5 - Median 41.0-39.0-40.0 - Minimum 28-23 - 23 - Maximum 45-45 - 45 -
Gender Female 17 56.7 18 60.0 35 58.3 Male 13 43.3 12 40.0 25 41.7 Geographic Ancestry African Heritage / African American 1 3.3 0 0.0 1 1.7 American Indian or Alaskan Native 0 0.0 0 0.0 0 0.0 Asian - Central / South Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - East Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - Japanese Heritage 0 0.0 0 0.0 0 0.0 Asian - South East Asian Heritage 0 0.0 0 0.0 0 0.0 Native Hawaiian or Other Pacific Islander 0 0.0 0 0.0 0 0.0 White - Arabic / North African Heritage 0 0.0 1 3.3 1 1.7 White - Caucasian / European Heritage 29 96.7 29 96.7 58 96.7 Other 0 0.0 0 0.0 0 0.0 Step 2 S2A Group N = 10 S2Alum Group N = 11 Total Group N = 21 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean 39.9-38.5-39.1 - SD 3.9-4.1-3.9 - Median 40.0-40.0-40.0 - Minimum 32-31 - 31 - Maximum 44-45 - 45 - Gender Female 8 80.0 8 72.7 16 76.2 Male 2 20.0 3 27.3 5 23.8 Geographic Ancestry African Heritage / African American 0 0.0 0 0.0 0 0.0 American Indian or Alaskan Native 0 0.0 0 0.0 0 0.0 Asian - Central / South Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - East Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - Japanese Heritage 0 0.0 0 0.0 0 0.0 Asian - South East Asian Heritage 0 0.0 0 0.0 0 0.0 Native Hawaiian or Other Pacific Islander 0 0.0 0 0.0 0 0.0 White - Arabic / North African Heritage 1 10.0 1 9.1 2 9.5 White - Caucasian / European Heritage 9 90.0 10 90.9 19 90.5 Other 0 0.0 0 0.0 0 0.0 Pooling Steps S1AS+S2AS N = 40 S1Alum+ S2Alum Group N = 41 Total N = 81 Value % Value % Value % Characteristics Parameters or Categories or n or n or n Age (years) at Dose 1 Mean 39.2-37.5-38.4 - SD 4.1-5.9-5.2 - Median 40.5-39.0-40.0 - Minimum 28-23 - 23 - Maximum 45-45 - 45 - Gender Female 25 62.5 26 63.4 51 63.0 Male 15 37.5 15 36.6 30 37.0 Geographic Ancestry African Heritage / African American 1 2.5 0 0.0 1 1.2 American Indian or Alaskan Native 0 0.0 0 0.0 0 0.0 Asian - Central / South Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - East Asian Heritage 0 0.0 0 0.0 0 0.0 Asian - Japanese Heritage 0 0.0 0 0.0 0 0.0 Asian - South East Asian Heritage 0 0.0 0 0.0 0 0.0 Native Hawaiian or Other Pacific Islander 0 0.0 0 0.0 0 0.0 White - Arabic / North African Heritage 1 2.5 2 4.9 3 3.7 White - Caucasian / European Heritage 38 95.0 39 95.1 77 95.1 Other 0 0.0 0 0.0 0 0.0
N = total number of subjects n/% = number / percentage of subjects in a given category Value = value of the considered parameter SD = standard deviation Primary Efficacy Results: Descriptive statistics of cytokines/chemokines concentrations (pg/ml) in plasma, by Multiplex (ATP cohort for innate immunogenicity up to Day 60) Step 1 Parameter Group Dose Time point N Q1 Median Q3 E-selectin S1AS Placebo PRE(D-30) 27 4600 6000 8300 PP(D-30 H1.5) 27 4100 5900 8500 PP(D-30 H3) 27 3800 5600 7800 PP(D-30 H6) 27 3900 5200 8300 PP(D-30 H9) 27 3600 5300 7100 PP(D-30 H12) 27 3500 5200 7900 PP(D-30 H18) 14 2900 4950 6500 PP(D-29) 27 4300 5900 8500 PP(D-28) 27 3700 5900 7800 PP(D-27) 26 3700 6150 8200 PP(D-23) 27 4000 5500 8300 Dose 1 PRE(D0) 27 4200 6100 9000 PI(D0 H1.5) 27 4000 5500 8400 PI(D0 H6) 27 4100 5400 7600 PI(D0 H12) 27 4400 5900 8800 PI(D0 H18) 14 3400 5750 8000 PI(D1) 26 4200 5950 9500 PI(D2) 27 4300 5800 9300 PI(D7) 27 4100 6600 8600 Dose 2 PI(D30) 27 4300 6200 9000 PII(D30 H1.5) 27 3900 6300 7600 PII(D30 H3) 26 4000 6550 8200 PII(D30 H6) 26 4200 6000 8100 PII(D30 H9) 27 4100 6200 7400 PII(D30 H12) 25 4000 5800 7800 PII(D30 H18) 14 3400 5400 8000 PII(D31) 27 4300 6800 8200 PII(D32) 27 4400 7000 9100 PII(D33) 27 4400 6400 8700 PII(D37) 27 4000 6200 8200 S1Alum Placebo PRE(D-30) 26 4600 6250 7800 PP(D-30 H1.5) 26 4500 6450 7600 PP(D-30 H3) 26 4100 6300 7600 PP(D-30 H6) 26 4200 6050 8100 PP(D-30 H9) 26 4600 6100 7500 PP(D-30 H12) 25 4000 5600 7800 PP(D-30 H18) 11 2700 4200 6300 PP(D-29) 26 4500 6350 8600 PP(D-28) 26 4300 6250 7900 PP(D-27) 26 4000 6250 7200 PP(D-23) 26 4700 6150 7900 Dose 1 PRE(D0) 26 5000 6150 8600 PI(D0 H1.5) 25 4800 5900 8100 PI(D0 H6) 26 4300 5900 7600 PI(D0 H12) 26 5000 6400 8000 PI(D0 H18) 11 3500 4700 5900 PI(D1) 25 4900 6000 8900 PI(D2) 25 5000 6300 7400 PI(D7) 26 4800 6700 8500
Dose 2 PI(D30) 25 5200 6500 8000 PII(D30 H1.5) 25 4900 5700 6800 PII(D30 H3) 24 4450 5700 6850 PII(D30 H6) 24 4550 5850 7000 PII(D30 H9) 24 4350 5500 6850 PII(D30 H12) 25 4500 5800 7000 PII(D30 H18) 11 2900 4500 5800 PII(D31) 25 5200 5800 7100 PII(D32) 25 4900 6000 8000 PII(D33) 25 5100 6300 8000 PII(D37) 25 5000 6000 7700 GM-CSF S1AS Placebo PRE(D-30) 27 14 14 14 PP(D-30 H1.5) 27 14 14 14 PP(D-30 H3) 27 14 14 14 PP(D-30 H6) 27 14 14 14 PP(D-30 H9) 27 14 14 14 PP(D-30 H12) 27 14 14 14 PP(D-30 H18) 14 14 14 14 PP(D-29) 27 14 14 14 PP(D-28) 27 14 14 14 PP(D-27) 26 14 14 14 PP(D-23) 27 14 14 14 Dose 1 PRE(D0) 27 14 14 14 PI(D0 H1.5) 27 14 14 14 PI(D0 H6) 27 14 14 14 PI(D0 H12) 27 14 14 14 PI(D0 H18) 14 14 14 14 PI(D1) 26 14 14 14 PI(D2) 27 14 14 14 PI(D7) 27 14 14 14 Dose 2 PI(D30) 27 14 14 14 PII(D30 H1.5) 27 14 14 14 PII(D30 H3) 26 14 14 14 PII(D30 H6) 26 14 14 14 PII(D30 H9) 27 14 14 14 PII(D30 H12) 25 14 14 14 PII(D30 H18) 14 14 14 14 PII(D31) 27 14 14 14 PII(D32) 27 14 14 14 PII(D33) 27 14 14 14 PII(D37) 27 14 14 14 S1Alum Placebo PRE(D-30) 26 14 14 14 PP(D-30 H1.5) 26 14 14 14 PP(D-30 H3) 26 14 14 14 PP(D-30 H6) 26 14 14 14 PP(D-30 H9) 26 14 14 14 PP(D-30 H12) 25 14 14 14 PP(D-30 H18) 11 14 14 14 PP(D-29) 26 14 14 14 PP(D-28) 26 14 14 14 PP(D-27) 26 14 14 14 PP(D-23) 26 14 14 14 Dose 1 PRE(D0) 26 14 14 14 PI(D0 H1.5) 25 14 14 14 PI(D0 H6) 26 14 14 14 PI(D0 H12) 26 14 14 14
PI(D0 H18) 11 14 14 14 PI(D1) 25 14 14 14 PI(D2) 25 14 14 14 PI(D7) 26 14 14 14 Dose 2 PI(D30) 25 14 14 14 PII(D30 H1.5) 25 14 14 14 PII(D30 H3) 24 14 14 14 PII(D30 H6) 24 14 14 14 PII(D30 H9) 24 14 14 14 PII(D30 H12) 25 14 14 14 PII(D30 H18) 11 14 14 14 PII(D31) 25 14 14 14 PII(D32) 25 14 14 14 PII(D33) 25 14 14 14 PII(D37) 25 14 14 14 IFN-γ S1AS Placebo PRE(D-30) 27 1.6 1.6 1.6 PP(D-30 H1.5) 27 1.6 1.6 1.6 PP(D-30 H3) 27 1.6 1.6 1.6 PP(D-30 H6) 27 1.6 1.6 1.6 PP(D-30 H9) 27 1.6 1.6 1.6 PP(D-30 H12) 27 1.6 1.6 1.6 PP(D-30 H18) 14 1.6 1.6 1.6 PP(D-29) 27 1.6 1.6 1.6 PP(D-28) 27 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.6 PP(D-23) 27 1.6 1.6 1.6 Dose 1 PRE(D0) 27 1.6 1.6 1.6 PI(D0 H1.5) 27 1.6 1.6 1.6 PI(D0 H6) 27 1.6 1.6 1.6 PI(D0 H12) 27 1.6 1.6 1.6 PI(D0 H18) 14 1.6 1.8 2.4 PI(D1) 26 1.6 1.6 1.6 PI(D2) 27 1.6 1.6 1.6 PI(D7) 27 1.6 1.6 1.6 Dose 2 PI(D30) 27 1.6 1.6 1.6 PII(D30 H1.5) 27 1.6 1.6 1.6 PII(D30 H3) 26 1.6 1.6 1.6 PII(D30 H6) 26 1.6 1.6 1.6 PII(D30 H9) 27 1.6 1.6 1.6 PII(D30 H12) 25 1.6 2.3 3.1 PII(D30 H18) 14 1.6 5.2 7.4 PII(D31) 27 1.7 4.8 8.6 PII(D32) 27 1.6 1.6 1.6 PII(D33) 27 1.6 1.6 1.6 PII(D37) 27 1.6 1.6 1.6 S1Alum Placebo PRE(D-30) 26 1.6 1.6 1.6 PP(D-30 H1.5) 26 1.6 1.6 1.6 PP(D-30 H3) 26 1.6 1.6 1.6 PP(D-30 H6) 26 1.6 1.6 1.6 PP(D-30 H9) 26 1.6 1.6 1.6 PP(D-30 H12) 25 1.6 1.6 1.6 PP(D-30 H18) 11 1.6 1.6 1.6 PP(D-29) 26 1.6 1.6 1.6 PP(D-28) 26 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.6 PP(D-23) 26 1.6 1.6 1.6
Dose 1 PRE(D0) 26 1.6 1.6 1.6 PI(D0 H1.5) 25 1.6 1.6 1.6 PI(D0 H6) 26 1.6 1.6 1.6 PI(D0 H12) 26 1.6 1.6 1.6 PI(D0 H18) 11 1.6 1.6 1.6 PI(D1) 25 1.6 1.6 1.6 PI(D2) 25 1.6 1.6 1.6 PI(D7) 26 1.6 1.6 1.6 Dose 2 PI(D30) 25 1.6 1.6 1.6 PII(D30 H1.5) 25 1.6 1.6 1.6 PII(D30 H3) 24 1.6 1.6 1.6 PII(D30 H6) 24 1.6 1.6 1.6 PII(D30 H9) 24 1.6 1.6 1.6 PII(D30 H12) 25 1.6 1.6 1.6 PII(D30 H18) 11 1.6 1.6 1.6 PII(D31) 25 1.6 1.6 1.6 PII(D32) 25 1.6 1.6 1.6 PII(D33) 25 1.6 1.6 1.6 PII(D37) 25 1.6 1.6 1.6 IL-10 S1AS Placebo PRE(D-30) 27 3.3 3.3 4.5 PP(D-30 H1.5) 27 3.3 3.3 3.7 PP(D-30 H3) 27 3.3 3.3 4.2 PP(D-30 H6) 27 3.3 3.3 4.6 PP(D-30 H9) 27 3.3 3.3 4.8 PP(D-30 H12) 27 3.3 3.3 3.3 PP(D-30 H18) 14 3.3 3.3 3.6 PP(D-29) 27 3.3 3.3 4.5 PP(D-28) 27 3.3 3.3 3.9 PP(D-27) 26 3.3 3.4 4.5 PP(D-23) 27 3.3 3.3 4.3 Dose 1 PRE(D0) 27 3.3 3.3 3.5 PI(D0 H1.5) 27 3.3 3.3 3.8 PI(D0 H6) 27 3.3 3.3 3.3 PI(D0 H12) 27 3.3 3.9 5.5 PI(D0 H18) 14 3.3 3.3 4.8 PI(D1) 26 3.6 5.2 6.8 PI(D2) 27 3.3 3.6 4.3 PI(D7) 27 3.3 3.6 4.9 Dose 2 PI(D30) 27 3.3 3.3 3.4 PII(D30 H1.5) 27 3.3 3.3 4.5 PII(D30 H3) 26 3.3 3.3 4.5 PII(D30 H6) 26 3.3 3.3 3.7 PII(D30 H9) 27 3.3 3.3 5.2 PII(D30 H12) 25 3.3 3.3 3.8 PII(D30 H18) 14 3.3 4.5 6 PII(D31) 27 3.3 4.8 6.3 PII(D32) 27 3.3 3.5 5.3 PII(D33) 27 3.3 3.3 3.6 PII(D37) 27 3.3 3.3 3.3 S1Alum Placebo PRE(D-30) 26 3.3 3.3 4.1 PP(D-30 H1.5) 26 3.3 3.3 3.7 PP(D-30 H3) 26 3.3 3.3 3.4 PP(D-30 H6) 26 3.3 3.3 3.6 PP(D-30 H9) 26 3.3 3.3 3.3 PP(D-30 H12) 25 3.3 3.3 3.3 PP(D-30 H18) 11 3.3 3.3 3.3
PP(D-29) 26 3.3 3.3 3.3 PP(D-28) 26 3.3 3.3 3.9 PP(D-27) 26 3.3 3.3 4.2 PP(D-23) 26 3.3 3.3 3.5 Dose 1 PRE(D0) 26 3.3 3.3 3.9 PI(D0 H1.5) 25 3.3 3.3 3.9 PI(D0 H6) 26 3.3 3.3 3.3 PI(D0 H12) 26 3.3 3.3 3.3 PI(D0 H18) 11 3.3 3.3 3.3 PI(D1) 25 3.3 3.3 3.6 PI(D2) 25 3.3 3.3 3.7 PI(D7) 26 3.3 3.3 3.9 Dose 2 PI(D30) 25 3.3 3.3 3.4 PII(D30 H1.5) 25 3.3 3.3 4.3 PII(D30 H3) 24 3.3 3.3 3.4 PII(D30 H6) 24 3.3 3.3 3.3 PII(D30 H9) 24 3.3 3.3 3.4 PII(D30 H12) 25 3.3 3.3 3.3 PII(D30 H18) 11 3.3 3.3 3.4 PII(D31) 25 3.3 3.3 3.3 PII(D32) 25 3.3 3.3 3.5 PII(D33) 25 3.3 3.3 3.6 PII(D37) 25 3.3 3.3 3.3 IL-18 S1AS Placebo PRE(D-30) 27 148 198 290 PP(D-30 H1.5) 27 141 172 225 PP(D-30 H3) 27 154 168 283 PP(D-30 H6) 27 160 176 273 PP(D-30 H9) 27 139 173 226 PP(D-30 H12) 27 150 171 244 PP(D-30 H18) 14 118 174 267 PP(D-29) 27 149 186 261 PP(D-28) 27 148 182 288 PP(D-27) 26 157 183 236 PP(D-23) 27 150 184 247 Dose 1 PRE(D0) 27 151 169 237 PI(D0 H1.5) 27 144 168 220 PI(D0 H6) 27 130 170 225 PI(D0 H12) 27 155 171 235 PI(D0 H18) 14 155 180 217 PI(D1) 26 167 198.5 267 PI(D2) 27 165 219 252 PI(D7) 27 168 202 265 Dose 2 PI(D30) 27 151 202 248 PII(D30 H1.5) 27 143 171 223 PII(D30 H3) 26 146 171.5 204 PII(D30 H6) 26 151 173.5 227 PII(D30 H9) 27 139 177 240 PII(D30 H12) 25 146 166 212 PII(D30 H18) 14 151 164.5 241 PII(D31) 27 151 185 258 PII(D32) 27 195 238 269 PII(D33) 27 195 256 351 PII(D37) 27 156 194 256 S1Alum Placebo PRE(D-30) 26 152 177 215 PP(D-30 H1.5) 26 136 179.5 215 PP(D-30 H3) 26 142 173 202
PP(D-30 H6) 26 132 177.5 233 PP(D-30 H9) 26 117 167.5 202 PP(D-30 H12) 25 131 180 222 PP(D-30 H18) 11 81 142 182 PP(D-29) 26 136 177.5 242 PP(D-28) 26 120 178.5 232 PP(D-27) 26 139 174.5 217 PP(D-23) 26 122 176.5 208 Dose 1 PRE(D0) 26 119 171 207 PI(D0 H1.5) 25 126 168 208 PI(D0 H6) 26 110 169 220 PI(D0 H12) 26 128 181.5 205 PI(D0 H18) 11 93 126 168 PI(D1) 25 123 181 200 PI(D2) 25 130 167 219 PI(D7) 26 126 191 231 Dose 2 PI(D30) 25 136 183 234 PII(D30 H1.5) 25 127 176 207 PII(D30 H3) 24 104 158 206.5 PII(D30 H6) 24 127.5 183 211.5 PII(D30 H9) 24 115 165 229.5 PII(D30 H12) 25 124 174 220 PII(D30 H18) 11 128 168 197 PII(D31) 25 137 166 217 PII(D32) 25 135 190 238 PII(D33) 25 142 181 231 PII(D37) 25 123 166 196 IL-2 S1AS Placebo PRE(D-30) 27 5.9 5.9 7 PP(D-30 H1.5) 27 5.9 5.9 7 PP(D-30 H3) 27 5.9 5.9 7.4 PP(D-30 H6) 27 5.9 5.9 5.9 PP(D-30 H9) 27 5.9 5.9 14 PP(D-30 H12) 27 5.9 5.9 6.3 PP(D-30 H18) 14 5.9 6 6.3 PP(D-29) 27 5.9 5.9 5.9 PP(D-28) 27 5.9 5.9 5.9 PP(D-27) 26 5.9 5.9 5.9 PP(D-23) 27 5.9 5.9 7 Dose 1 PRE(D0) 27 5.9 5.9 6.5 PI(D0 H1.5) 27 5.9 5.9 5.9 PI(D0 H6) 27 5.9 5.9 6 PI(D0 H12) 27 5.9 5.9 6.5 PI(D0 H18) 14 5.9 5.9 6 PI(D1) 26 5.9 5.9 5.9 PI(D2) 27 5.9 5.9 5.9 PI(D7) 27 5.9 5.9 5.9 Dose 2 PI(D30) 27 5.9 5.9 5.9 PII(D30 H1.5) 27 5.9 5.9 5.9 PII(D30 H3) 26 5.9 5.9 5.9 PII(D30 H6) 26 5.9 5.9 5.9 PII(D30 H9) 27 5.9 5.9 5.9 PII(D30 H12) 25 5.9 5.9 5.9 PII(D30 H18) 14 5.9 5.9 5.9 PII(D31) 27 5.9 8.5 8.5 PII(D32) 27 5.9 5.9 7 PII(D33) 27 5.9 5.9 5.9
PII(D37) 27 5.9 5.9 5.9 S1Alum Placebo PRE(D-30) 26 5.9 5.9 5.9 PP(D-30 H1.5) 26 5.9 5.9 6.3 PP(D-30 H3) 26 5.9 5.9 5.9 PP(D-30 H6) 26 5.9 5.9 6 PP(D-30 H9) 26 5.9 5.9 7.2 PP(D-30 H12) 25 5.9 5.9 6.3 PP(D-30 H18) 11 5.9 5.9 6 PP(D-29) 26 5.9 5.9 5.9 PP(D-28) 26 5.9 5.9 5.9 PP(D-27) 26 5.9 5.9 5.9 PP(D-23) 26 5.9 5.9 7 Dose 1 PRE(D0) 26 5.9 5.9 6.5 PI(D0 H1.5) 25 5.9 5.9 7.4 PI(D0 H6) 26 5.9 5.9 6 PI(D0 H12) 26 5.9 5.9 6 PI(D0 H18) 11 5.9 5.9 6 PI(D1) 25 5.9 5.9 5.9 PI(D2) 25 5.9 5.9 5.9 PI(D7) 26 5.9 5.9 5.9 Dose 2 PI(D30) 25 5.9 5.9 5.9 PII(D30 H1.5) 25 5.9 5.9 5.9 PII(D30 H3) 24 5.9 5.9 5.9 PII(D30 H6) 24 5.9 5.9 5.9 PII(D30 H9) 24 5.9 5.9 6.6 PII(D30 H12) 25 5.9 5.9 5.9 PII(D30 H18) 11 5.9 5.9 5.9 PII(D31) 25 5.9 5.9 8.5 PII(D32) 25 5.9 5.9 7 PII(D33) 25 5.9 5.9 5.9 PII(D37) 25 5.9 5.9 5.9 IL-3 S1AS Placebo PRE(D-30) 27 1.6 1.6 1.6 PP(D-30 H1.5) 27 1.6 1.6 1.6 PP(D-30 H3) 27 1.6 1.6 1.6 PP(D-30 H6) 27 1.6 1.6 1.6 PP(D-30 H9) 27 1.6 1.6 1.6 PP(D-30 H12) 27 1.6 1.6 1.6 PP(D-30 H18) 14 1.6 1.6 1.6 PP(D-29) 27 1.6 1.6 1.6 PP(D-28) 27 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.6 PP(D-23) 27 1.6 1.6 1.6 Dose 1 PRE(D0) 27 1.6 1.6 1.6 PI(D0 H1.5) 27 1.6 1.6 1.6 PI(D0 H6) 27 1.6 1.6 1.6 PI(D0 H12) 27 1.6 1.6 1.6 PI(D0 H18) 14 1.6 1.6 1.6 PI(D1) 26 1.6 1.6 1.6 PI(D2) 27 1.6 1.6 1.6 PI(D7) 27 1.6 1.6 1.6 Dose 2 PI(D30) 27 1.6 1.6 1.6 PII(D30 H1.5) 27 1.6 1.6 1.6 PII(D30 H3) 26 1.6 1.6 1.6 PII(D30 H6) 26 1.6 1.6 1.6 PII(D30 H9) 27 1.6 1.6 1.6 PII(D30 H12) 25 1.6 1.6 1.6
PII(D30 H18) 14 1.6 1.6 1.6 PII(D31) 27 1.6 1.6 1.6 PII(D32) 27 1.6 1.6 1.6 PII(D33) 27 1.6 1.6 1.6 PII(D37) 27 1.6 1.6 1.6 S1Alum Placebo PRE(D-30) 26 1.6 1.6 1.6 PP(D-30 H1.5) 26 1.6 1.6 1.6 PP(D-30 H3) 26 1.6 1.6 1.6 PP(D-30 H6) 26 1.6 1.6 1.6 PP(D-30 H9) 26 1.6 1.6 1.6 PP(D-30 H12) 25 1.6 1.6 1.6 PP(D-30 H18) 11 1.6 1.6 1.6 PP(D-29) 26 1.6 1.6 1.6 PP(D-28) 26 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.6 PP(D-23) 26 1.6 1.6 1.6 Dose 1 PRE(D0) 26 1.6 1.6 1.6 PI(D0 H1.5) 25 1.6 1.6 1.6 PI(D0 H6) 26 1.6 1.6 1.6 PI(D0 H12) 26 1.6 1.6 1.6 PI(D0 H18) 11 1.6 1.6 1.6 PI(D1) 25 1.6 1.6 1.6 PI(D2) 25 1.6 1.6 1.6 PI(D7) 26 1.6 1.6 1.6 Dose 2 PI(D30) 25 1.6 1.6 1.6 PII(D30 H1.5) 25 1.6 1.6 1.6 PII(D30 H3) 24 1.6 1.6 1.6 PII(D30 H6) 24 1.6 1.6 1.6 PII(D30 H9) 24 1.6 1.6 1.6 PII(D30 H12) 25 1.6 1.6 1.6 PII(D30 H18) 11 1.6 1.6 1.6 PII(D31) 25 1.6 1.6 1.6 PII(D32) 25 1.6 1.6 1.6 PII(D33) 25 1.6 1.6 1.6 PII(D37) 25 1.6 1.6 1.6 IL-4 S1AS Placebo PRE(D-30) 27 9.4 9.4 9.4 PP(D-30 H1.5) 27 9.4 9.4 9.4 PP(D-30 H3) 27 9.4 9.4 9.4 PP(D-30 H6) 27 9.4 9.4 9.4 PP(D-30 H9) 27 9.4 9.4 9.4 PP(D-30 H12) 27 9.4 9.4 9.4 PP(D-30 H18) 14 9.4 9.4 9.4 PP(D-29) 27 9.4 9.4 9.4 PP(D-28) 27 9.4 9.4 9.4 PP(D-27) 26 9.4 9.4 9.4 PP(D-23) 27 9.4 9.4 9.4 Dose 1 PRE(D0) 27 9.4 9.4 9.4 PI(D0 H1.5) 27 9.4 9.4 9.4 PI(D0 H6) 27 9.4 9.4 9.4 PI(D0 H12) 27 9.4 9.4 9.4 PI(D0 H18) 14 9.4 9.4 9.4 PI(D1) 26 9.4 9.4 9.4 PI(D2) 27 9.4 9.4 9.4 PI(D7) 27 9.4 9.4 9.4 Dose 2 PI(D30) 27 9.4 9.4 9.4 PII(D30 H1.5) 27 9.4 9.4 9.4
PII(D30 H3) 26 9.4 9.4 9.4 PII(D30 H6) 26 9.4 9.4 9.4 PII(D30 H9) 27 9.4 9.4 9.4 PII(D30 H12) 25 9.4 9.4 9.4 PII(D30 H18) 14 9.4 9.4 9.4 PII(D31) 27 9.4 9.4 9.4 PII(D32) 27 9.4 9.4 9.4 PII(D33) 27 9.4 9.4 9.4 PII(D37) 27 9.4 9.4 9.4 S1Alum Placebo PRE(D-30) 26 9.4 9.4 9.4 PP(D-30 H1.5) 26 9.4 9.4 9.4 PP(D-30 H3) 26 9.4 9.4 9.4 PP(D-30 H6) 26 9.4 9.4 9.4 PP(D-30 H9) 26 9.4 9.4 9.4 PP(D-30 H12) 25 9.4 9.4 9.4 PP(D-30 H18) 11 9.4 9.4 9.4 PP(D-29) 26 9.4 9.4 9.4 PP(D-28) 26 9.4 9.4 9.4 PP(D-27) 26 9.4 9.4 9.4 PP(D-23) 26 9.4 9.4 9.4 Dose 1 PRE(D0) 26 9.4 9.4 9.4 PI(D0 H1.5) 25 9.4 9.4 9.4 PI(D0 H6) 26 9.4 9.4 9.4 PI(D0 H12) 26 9.4 9.4 9.4 PI(D0 H18) 11 9.4 9.4 9.4 PI(D1) 25 9.4 9.4 9.4 PI(D2) 25 9.4 9.4 9.4 PI(D7) 26 9.4 9.4 9.4 Dose 2 PI(D30) 25 9.4 9.4 9.4 PII(D30 H1.5) 25 9.4 9.4 9.4 PII(D30 H3) 24 9.4 9.4 9.4 PII(D30 H6) 24 9.4 9.4 9.4 PII(D30 H9) 24 9.4 9.4 9.4 PII(D30 H12) 25 9.4 9.4 9.4 PII(D30 H18) 11 9.4 9.4 9.4 PII(D31) 25 9.4 9.4 9.4 PII(D32) 25 9.4 9.4 9.4 PII(D33) 25 9.4 9.4 9.4 PII(D37) 25 9.4 9.4 9.4 IL-5 S1AS Placebo PRE(D-30) 27 2.7 2.7 2.7 PP(D-30 H1.5) 27 2.7 2.7 2.7 PP(D-30 H3) 27 2.7 2.7 2.7 PP(D-30 H6) 27 2.7 2.7 2.7 PP(D-30 H9) 27 2.7 2.7 2.7 PP(D-30 H12) 27 2.7 2.7 2.7 PP(D-30 H18) 14 2.7 2.7 2.7 PP(D-29) 27 2.7 2.7 2.7 PP(D-28) 27 2.7 2.7 2.7 PP(D-27) 26 2.7 2.7 2.7 PP(D-23) 27 2.7 2.7 2.7 Dose 1 PRE(D0) 27 2.7 2.7 2.7 PI(D0 H1.5) 27 2.7 2.7 2.7 PI(D0 H6) 27 2.7 2.7 2.7 PI(D0 H12) 27 2.7 2.7 2.7 PI(D0 H18) 14 2.7 2.7 2.7 PI(D1) 26 2.7 2.7 2.7
PI(D2) 27 2.7 2.7 2.7 PI(D7) 27 2.7 2.7 2.7 Dose 2 PI(D30) 27 2.7 2.7 2.7 PII(D30 H1.5) 27 2.7 2.7 2.7 PII(D30 H3) 26 2.7 2.7 2.7 PII(D30 H6) 26 2.7 2.7 2.7 PII(D30 H9) 27 2.7 2.7 2.7 PII(D30 H12) 25 2.7 2.7 2.7 PII(D30 H18) 14 2.7 2.7 2.7 PII(D31) 27 2.7 2.7 2.7 PII(D32) 27 2.7 2.7 2.7 PII(D33) 27 2.7 2.7 2.7 PII(D37) 27 2.7 2.7 2.7 S1Alum Placebo PRE(D-30) 26 2.7 2.7 2.7 PP(D-30 H1.5) 26 2.7 2.7 2.7 PP(D-30 H3) 26 2.7 2.7 2.7 PP(D-30 H6) 26 2.7 2.7 2.7 PP(D-30 H9) 26 2.7 2.7 2.7 PP(D-30 H12) 25 2.7 2.7 2.7 PP(D-30 H18) 11 2.7 2.7 2.7 PP(D-29) 26 2.7 2.7 2.7 PP(D-28) 26 2.7 2.7 2.7 PP(D-27) 26 2.7 2.7 2.7 PP(D-23) 26 2.7 2.7 2.7 Dose 1 PRE(D0) 26 2.7 2.7 2.7 PI(D0 H1.5) 25 2.7 2.7 2.7 PI(D0 H6) 26 2.7 2.7 2.7 PI(D0 H12) 26 2.7 2.7 2.7 PI(D0 H18) 11 2.7 2.7 2.7 PI(D1) 25 2.7 2.7 2.7 PI(D2) 25 2.7 2.7 2.7 PI(D7) 26 2.7 2.7 2.7 Dose 2 PI(D30) 25 2.7 2.7 2.7 PII(D30 H1.5) 25 2.7 2.7 2.7 PII(D30 H3) 24 2.7 2.7 2.7 PII(D30 H6) 24 2.7 2.7 2.7 PII(D30 H9) 24 2.7 2.7 2.7 PII(D30 H12) 25 2.7 2.7 2.7 PII(D30 H18) 11 2.7 2.7 2.7 PII(D31) 25 2.7 2.7 2.7 PII(D32) 25 2.7 2.7 2.7 PII(D33) 25 2.7 2.7 2.7 PII(D37) 25 2.7 2.7 2.7 IL-6 S1AS Placebo PRE(D-30) 27 1.6 1.6 1.6 PP(D-30 H1.5) 27 1.6 1.6 1.6 PP(D-30 H3) 27 1.6 1.6 1.6 PP(D-30 H6) 27 1.6 1.6 2 PP(D-30 H9) 27 1.6 1.6 2.7 PP(D-30 H12) 27 1.6 1.6 1.6 PP(D-30 H18) 14 1.6 1.6 1.6 PP(D-29) 27 1.6 1.6 1.7 PP(D-28) 27 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.7 PP(D-23) 27 1.6 1.6 1.6 Dose 1 PRE(D0) 27 1.6 1.6 1.6 PI(D0 H1.5) 27 1.6 1.6 1.6
PI(D0 H6) 27 2.4 3.4 6 PI(D0 H12) 27 3.9 6.3 8.2 PI(D0 H18) 14 3.1 4.5 6.9 PI(D1) 26 1.6 3 4.1 PI(D2) 27 1.6 1.6 1.6 PI(D7) 27 1.6 1.6 1.6 Dose 2 PI(D30) 27 1.6 1.6 2.3 PII(D30 H1.5) 27 1.6 1.6 1.6 PII(D30 H3) 26 1.6 1.6 2.5 PII(D30 H6) 26 2.8 4.4 6.7 PII(D30 H9) 27 3.2 4.8 6.7 PII(D30 H12) 25 5 6.4 9 PII(D30 H18) 14 4.2 6.3 8.3 PII(D31) 27 1.7 3.6 7.2 PII(D32) 27 1.6 1.6 2.5 PII(D33) 27 1.6 1.6 1.6 PII(D37) 27 1.6 1.6 1.6 S1Alum Placebo PRE(D-30) 26 1.6 1.6 1.6 PP(D-30 H1.5) 26 1.6 1.6 1.6 PP(D-30 H3) 26 1.6 1.6 1.6 PP(D-30 H6) 26 1.6 1.6 1.6 PP(D-30 H9) 26 1.6 1.6 1.6 PP(D-30 H12) 25 1.6 1.6 1.6 PP(D-30 H18) 11 1.6 1.6 2.4 PP(D-29) 26 1.6 1.6 1.7 PP(D-28) 26 1.6 1.6 1.6 PP(D-27) 26 1.6 1.6 1.7 PP(D-23) 26 1.6 1.6 1.6 Dose 1 PRE(D0) 26 1.6 1.6 1.6 PI(D0 H1.5) 25 1.6 1.6 1.6 PI(D0 H6) 26 1.6 1.6 1.7 PI(D0 H12) 26 1.6 1.6 1.6 PI(D0 H18) 11 1.6 1.6 1.6 PI(D1) 25 1.6 1.6 1.6 PI(D2) 25 1.6 1.6 1.6 PI(D7) 26 1.6 1.6 1.6 Dose 2 PI(D30) 25 1.6 1.6 1.6 PII(D30 H1.5) 25 1.6 1.6 1.6 PII(D30 H3) 24 1.6 1.6 1.6 PII(D30 H6) 24 1.6 1.6 1.6 PII(D30 H9) 24 1.6 1.6 1.6 PII(D30 H12) 25 1.6 1.6 1.7 PII(D30 H18) 11 1.6 1.6 1.6 PII(D31) 25 1.6 1.6 1.6 PII(D32) 25 1.6 1.6 1.6 PII(D33) 25 1.6 1.6 1.6 PII(D37) 25 1.6 1.6 1.6 IL-6r S1AS Placebo PRE(D-30) 27 20000 26000 30000 PP(D-30 H1.5) 27 21000 26000 30000 PP(D-30 H3) 27 22000 28000 34000 PP(D-30 H6) 27 21000 27000 32000 PP(D-30 H9) 27 19000 24000 31000 PP(D-30 H12) 27 21000 26000 32000 PP(D-30 H18) 14 18000 21500 29000 PP(D-29) 27 19000 27000 35000 PP(D-28) 27 20000 27000 35000
PP(D-27) 26 21000 26000 32000 PP(D-23) 27 17000 27000 31000 Dose 1 PRE(D0) 27 20000 27000 32000 PI(D0 H1.5) 27 21000 26000 32000 PI(D0 H6) 27 20000 26000 33000 PI(D0 H12) 27 21000 26000 32000 PI(D0 H18) 14 17000 22500 26000 PI(D1) 26 22000 26500 35000 PI(D2) 27 18000 25000 33000 PI(D7) 27 21000 27000 35000 Dose 2 PI(D30) 27 20000 27000 32000 PII(D30 H1.5) 27 18000 24000 30000 PII(D30 H3) 26 18000 26000 31000 PII(D30 H6) 26 18000 23000 29000 PII(D30 H9) 27 17000 23000 30000 PII(D30 H12) 25 21000 23000 31000 PII(D30 H18) 14 13000 19500 24000 PII(D31) 27 17000 26000 33000 PII(D32) 27 21000 27000 32000 PII(D33) 27 21000 26000 33000 PII(D37) 27 16000 28000 35000 S1Alum Placebo PRE(D-30) 26 20000 22500 30000 PP(D-30 H1.5) 26 19000 22000 29000 PP(D-30 H3) 26 21000 26000 33000 PP(D-30 H6) 26 20000 24500 33000 PP(D-30 H9) 26 19000 26000 29000 PP(D-30 H12) 25 21000 24000 34000 PP(D-30 H18) 11 18000 21000 28000 PP(D-29) 26 19000 26500 31000 PP(D-28) 26 20000 25500 28000 PP(D-27) 26 21000 24000 29000 PP(D-23) 26 19000 23500 28000 Dose 1 PRE(D0) 26 22000 24500 29000 PI(D0 H1.5) 25 19000 25000 29000 PI(D0 H6) 25 22000 25000 30000 PI(D0 H12) 26 22000 24000 33000 PI(D0 H18) 11 19000 22000 31000 PI(D1) 24 21500 24500 31000 PI(D2) 25 20000 24000 30000 PI(D7) 26 21000 25000 31000 Dose 2 PI(D30) 25 21000 26000 30000 PII(D30 H1.5) 25 20000 25000 31000 PII(D30 H3) 24 19000 23000 28500 PII(D30 H6) 24 20500 24500 30500 PII(D30 H9) 24 18500 24500 30500 PII(D30 H12) 25 21000 24000 32000 PII(D30 H18) 11 17000 24000 32000 PII(D31) 25 22000 24000 31000 PII(D32) 25 21000 24000 31000 PII(D33) 25 21000 25000 28000 PII(D37) 25 20000 25000 27000 IL-7 S1AS Placebo PRE(D-30) 27 8.2 8.2 8.2 PP(D-30 H1.5) 27 8.2 8.2 8.2 PP(D-30 H3) 27 8.2 8.2 8.2 PP(D-30 H6) 27 8.2 8.2 8.2 PP(D-30 H9) 27 8.2 8.2 8.2
PP(D-30 H12) 27 8.2 8.2 8.2 PP(D-30 H18) 14 8.2 8.2 8.2 PP(D-29) 27 8.2 8.2 8.2 PP(D-28) 27 8.2 8.2 8.2 PP(D-27) 26 8.2 8.2 8.2 PP(D-23) 27 8.2 8.2 8.2 Dose 1 PRE(D0) 27 8.2 8.2 8.2 PI(D0 H1.5) 27 8.2 8.2 8.2 PI(D0 H6) 27 8.2 8.2 8.2 PI(D0 H12) 27 8.2 8.2 8.2 PI(D0 H18) 14 8.2 8.2 8.2 PI(D1) 26 8.2 8.2 8.2 PI(D2) 27 8.2 8.2 8.2 PI(D7) 27 8.2 8.2 8.2 Dose 2 PI(D30) 27 8.2 8.2 8.2 PII(D30 H1.5) 27 8.2 8.2 8.2 PII(D30 H3) 26 8.2 8.2 8.2 PII(D30 H6) 26 8.2 8.2 8.2 PII(D30 H9) 27 8.2 8.2 8.2 PII(D30 H12) 25 8.2 8.2 8.2 PII(D30 H18) 14 8.2 8.2 8.2 PII(D31) 27 8.2 8.2 8.2 PII(D32) 27 8.2 8.2 8.2 PII(D33) 27 8.2 8.2 8.2 PII(D37) 27 8.2 8.2 8.2 S1Alum Placebo PRE(D-30) 26 8.2 8.2 8.2 PP(D-30 H1.5) 26 8.2 8.2 8.2 PP(D-30 H3) 26 8.2 8.2 8.2 PP(D-30 H6) 26 8.2 8.2 8.2 PP(D-30 H9) 26 8.2 8.2 8.2 PP(D-30 H12) 25 8.2 8.2 8.2 PP(D-30 H18) 11 8.2 8.2 8.2 PP(D-29) 26 8.2 8.2 8.2 PP(D-28) 26 8.2 8.2 8.2 PP(D-27) 26 8.2 8.2 8.2 PP(D-23) 26 8.2 8.2 8.2 Dose 1 PRE(D0) 26 8.2 8.2 8.2 PI(D0 H1.5) 25 8.2 8.2 8.2 PI(D0 H6) 26 8.2 8.2 8.2 PI(D0 H12) 26 8.2 8.2 8.2 PI(D0 H18) 11 8.2 8.2 8.2 PI(D1) 25 8.2 8.2 8.2 PI(D2) 25 8.2 8.2 8.2 PI(D7) 26 8.2 8.2 8.2 Dose 2 PI(D30) 25 8.2 8.2 8.2 PII(D30 H1.5) 25 8.2 8.2 8.2 PII(D30 H3) 24 8.2 8.2 8.2 PII(D30 H6) 24 8.2 8.2 8.2 PII(D30 H9) 24 8.2 8.2 8.2 PII(D30 H12) 25 8.2 8.2 8.2 PII(D30 H18) 11 8.2 8.2 8.2 PII(D31) 25 8.2 8.2 8.2 PII(D32) 25 8.2 8.2 8.2 PII(D33) 25 8.2 8.2 8.2 PII(D37) 25 8.2 8.2 8.2 IL-8 S1AS Placebo PRE(D-30) 27 4.2 5.7 6.6
PP(D-30 H1.5) 27 3.7 4.2 4.9 PP(D-30 H3) 27 3.5 4.2 6.4 PP(D-30 H6) 27 3.7 4.5 6 PP(D-30 H9) 27 3.7 4.9 6.9 PP(D-30 H12) 27 3.9 4.6 5.9 PP(D-30 H18) 14 4.6 5.5 8.2 PP(D-29) 27 3.9 5.4 6.9 PP(D-28) 27 3.7 4.8 6.5 PP(D-27) 26 3.4 4.3 6.6 PP(D-23) 27 3.9 4.5 6.8 Dose 1 PRE(D0) 27 4.2 4.9 6.2 PI(D0 H1.5) 27 3.6 4.9 5.5 PI(D0 H6) 27 3.9 4.6 5.5 PI(D0 H12) 27 3.5 4.2 5.1 PI(D0 H18) 14 4.5 5.9 6.4 PI(D1) 26 4.1 5.1 6.3 PI(D2) 27 3.8 4.8 6.4 PI(D7) 27 4.2 5 6.9 Dose 2 PI(D30) 27 3.9 4.8 6 PII(D30 H1.5) 27 3 3.2 5.6 PII(D30 H3) 26 3.9 4.7 6 PII(D30 H6) 26 3.5 5.2 6.7 PII(D30 H9) 27 3.2 4.1 5.5 PII(D30 H12) 25 4.1 4.9 6 PII(D30 H18) 14 4.1 4.8 5.4 PII(D31) 27 4.8 5.6 7 PII(D32) 27 4.3 5.5 6.5 PII(D33) 27 4.3 5.5 7.4 PII(D37) 27 3.9 5.3 6.6 S1Alum Placebo PRE(D-30) 26 3.9 5.1 5.9 PP(D-30 H1.5) 26 3.2 4.2 5.3 PP(D-30 H3) 26 3.2 4 5.3 PP(D-30 H6) 26 3.9 4.5 5.8 PP(D-30 H9) 26 3.6 4.5 5.3 PP(D-30 H12) 25 3.9 4.5 5.8 PP(D-30 H18) 11 4.9 6.1 7.8 PP(D-29) 26 4.3 5.2 6.8 PP(D-28) 26 3.5 4.9 6.6 PP(D-27) 26 3.6 4.2 5.4 PP(D-23) 26 3.5 5 5.8 Dose 1 PRE(D0) 26 4.2 5 7.4 PI(D0 H1.5) 25 3.3 4.2 5.1 PI(D0 H6) 26 3.9 4.6 7.2 PI(D0 H12) 26 4 4.8 5.6 PI(D0 H18) 11 4.2 5.1 6 PI(D1) 25 3.8 4.4 5.6 PI(D2) 25 4.2 5 5.6 PI(D7) 26 4.2 5.1 6.7 Dose 2 PI(D30) 25 3.4 4.3 5.8 PII(D30 H1.5) 25 2.7 4.3 5 PII(D30 H3) 24 3.8 4.5 5 PII(D30 H6) 24 3.5 4.5 5.2 PII(D30 H9) 24 3.2 4 5.4 PII(D30 H12) 25 3.2 5.2 6 PII(D30 H18) 11 3.5 5 5.9 PII(D31) 25 3.9 4.8 5.9
PII(D32) 25 4 5.1 6.5 PII(D33) 25 4.3 5.5 6.2 PII(D37) 25 4.6 5.5 6 IP-10 S1AS Placebo PRE(D-30) 27 176 225 402 PP(D-30 H1.5) 27 183 220 330 PP(D-30 H3) 27 169 223 396 PP(D-30 H6) 27 177 217 400 PP(D-30 H9) 27 162 210 327 PP(D-30 H12) 27 160 217 335 PP(D-30 H18) 14 174 243.5 386 PP(D-29) 27 190 241 345 PP(D-28) 27 205 270 381 PP(D-27) 26 189 239 348 PP(D-23) 27 190 241 366 Dose 1 PRE(D0) 27 199 243 294 PI(D0 H1.5) 27 198 224 318 PI(D0 H6) 27 179 207 270 PI(D0 H12) 27 197 236 281 PI(D0 H18) 14 268 319 477 PI(D1) 26 251 295 414 PI(D2) 27 291 455 569 PI(D7) 27 178 235 350 Dose 2 PI(D30) 27 211 245 349 PII(D30 H1.5) 27 189 223 336 PII(D30 H3) 26 182 208 275 PII(D30 H6) 26 182 210.5 248 PII(D30 H9) 27 180 217 326 PII(D30 H12) 25 228 240 335 PII(D30 H18) 14 296 589.5 715 PII(D31) 27 405 763 1130 PII(D32) 27 492 760 993 PII(D33) 27 288 366 524 PII(D37) 27 213 259 296 S1Alum Placebo PRE(D-30) 26 195 247.5 280 PP(D-30 H1.5) 26 172 207 240 PP(D-30 H3) 26 175 217.5 251 PP(D-30 H6) 26 174 218 252 PP(D-30 H9) 26 159 205.5 227 PP(D-30 H12) 25 182 214 246 PP(D-30 H18) 11 170 238 483 PP(D-29) 26 200 244.5 307 PP(D-28) 26 186 228 304 PP(D-27) 26 186 220.5 281 PP(D-23) 26 186 223 285 Dose 1 PRE(D0) 26 178 225 334 PI(D0 H1.5) 25 186 226 265 PI(D0 H6) 26 180 204 282 PI(D0 H12) 26 167 194 282 PI(D0 H18) 11 184 228 258 PI(D1) 25 179 219 326 PI(D2) 25 174 214 303 PI(D7) 26 185 220.5 279 Dose 2 PI(D30) 25 183 235 264 PII(D30 H1.5) 25 173 215 247 PII(D30 H3) 24 176 205.5 243.5 PII(D30 H6) 24 160 196.5 248.5
PII(D30 H9) 24 168 204 234 PII(D30 H12) 25 166 200 240 PII(D30 H18) 11 196 216 430 PII(D31) 25 197 212 270 PII(D32) 25 192 226 276 PII(D33) 25 220 249 319 PII(D37) 25 179 223 289 MCP-1 S1AS Placebo PRE(D-30) 27 89 107 142 PP(D-30 H1.5) 27 58 79 101 PP(D-30 H3) 27 65 79 92 PP(D-30 H6) 27 76 104 119 PP(D-30 H9) 27 65 86 104 PP(D-30 H12) 27 79 117 133 PP(D-30 H18) 14 76 98 119 PP(D-29) 27 73 93 116 PP(D-28) 27 56 74 112 PP(D-27) 26 65 84.5 110 PP(D-23) 27 55 88 143 Dose 1 PRE(D0) 27 75 94 121 PI(D0 H1.5) 27 56 74 97 PI(D0 H6) 27 75 94 123 PI(D0 H12) 27 87 111 137 PI(D0 H18) 14 91 111 130 PI(D1) 26 67 85.5 101 PI(D2) 27 55 83 95 PI(D7) 27 73 94 119 Dose 2 PI(D30) 27 72 99 136 PII(D30 H1.5) 27 58 85 112 PII(D30 H3) 26 62 75 95 PII(D30 H6) 26 98 116.5 132 PII(D30 H9) 27 88 103 119 PII(D30 H12) 25 96 117 150 PII(D30 H18) 14 76 104.5 116 PII(D31) 27 79 101 137 PII(D32) 27 55 75 94 PII(D33) 27 65 85 101 PII(D37) 27 66 83 109 S1Alum Placebo PRE(D-30) 26 83 98.5 117 PP(D-30 H1.5) 26 63 77.5 96 PP(D-30 H3) 26 48 64 104 PP(D-30 H6) 26 76 101 129 PP(D-30 H9) 26 61 81 109 PP(D-30 H12) 25 96 120 137 PP(D-30 H18) 11 79 109 132 PP(D-29) 26 66 81.5 104 PP(D-28) 26 47 73.5 90 PP(D-27) 26 73 86.5 109 PP(D-23) 26 66 72 96 Dose 1 PRE(D0) 26 80 92.5 125 PI(D0 H1.5) 25 56 75 108 PI(D0 H6) 26 66 85 112 PI(D0 H12) 26 84 111.5 129 PI(D0 H18) 11 98 115 130 PI(D1) 25 73 92 112 PI(D2) 25 58 79 101 PI(D7) 26 71 88.5 125
Dose 2 PI(D30) 25 72 86 111 PII(D30 H1.5) 25 66 87 104 PII(D30 H3) 24 51 75 85 PII(D30 H6) 24 79 95 121 PII(D30 H9) 24 55 80 106 PII(D30 H12) 25 71 95 121 PII(D30 H18) 11 91 96 106 PII(D31) 25 60 71 93 PII(D32) 25 65 77 121 PII(D33) 25 77 93 131 PII(D37) 25 63 85 99 MCP-2 S1AS Placebo PRE(D-30) 27 13 18 25 PP(D-30 H1.5) 27 13 17 24 PP(D-30 H3) 27 14 21 27 PP(D-30 H6) 27 14 18 24 PP(D-30 H9) 27 15 17 24 PP(D-30 H12) 27 14 18 26 PP(D-30 H18) 14 12 18 26 PP(D-29) 27 15 19 24 PP(D-28) 27 13 19 26 PP(D-27) 26 14 18.5 22 PP(D-23) 27 14 15 25 Dose 1 PRE(D0) 27 14 18 22 PI(D0 H1.5) 27 14 18 23 PI(D0 H6) 27 15 18 20 PI(D0 H12) 27 15 19 27 PI(D0 H18) 14 19 29.5 34 PI(D1) 26 16 21 26 PI(D2) 27 17 22 25 PI(D7) 27 16 20 24 Dose 2 PI(D30) 27 14 16 23 PII(D30 H1.5) 27 12 15 23 PII(D30 H3) 26 12 15.5 27 PII(D30 H6) 26 12 17 24 PII(D30 H9) 27 14 18 24 PII(D30 H12) 25 14 20 26 PII(D30 H18) 14 19 33 54 PII(D31) 27 19 35 67 PII(D32) 27 17 24 31 PII(D33) 27 16 20 28 PII(D37) 27 13 17 23 S1Alum Placebo PRE(D-30) 26 17 19.5 26 PP(D-30 H1.5) 26 14 19 25 PP(D-30 H3) 26 18 20 23 PP(D-30 H6) 26 16 20.5 23 PP(D-30 H9) 26 15 17 21 PP(D-30 H12) 25 17 19 25 PP(D-30 H18) 11 16 17 27 PP(D-29) 26 16 19 25 PP(D-28) 26 15 18.5 26 PP(D-27) 26 15 20 25 PP(D-23) 26 16 19 23 Dose 1 PRE(D0) 26 16 19 28 PI(D0 H1.5) 25 16 20 22 PI(D0 H6) 26 16 18.5 23 PI(D0 H12) 26 15 19.5 25
PI(D0 H18) 11 17 20 22 PI(D1) 25 17 20 25 PI(D2) 25 15 20 25 PI(D7) 26 18 22.5 30 Dose 2 PI(D30) 25 14 20 24 PII(D30 H1.5) 25 15 18 22 PII(D30 H3) 24 14.5 18 22.5 PII(D30 H6) 24 15 18.5 24 PII(D30 H9) 24 14.5 18.5 20.5 PII(D30 H12) 25 15 18 22 PII(D30 H18) 11 16 22 23 PII(D31) 25 14 17 19 PII(D32) 25 17 21 25 PII(D33) 25 17 20 26 PII(D37) 25 16 20 24 MCP-4 S1AS Placebo PRE(D-30) 27 1070 1230 1550 PP(D-30 H1.5) 27 933 1300 1480 PP(D-30 H3) 27 951 1170 1440 PP(D-30 H6) 27 1030 1310 1570 PP(D-30 H9) 27 1050 1310 1610 PP(D-30 H12) 27 1000 1260 1480 PP(D-30 H18) 14 1130 1445 1640 PP(D-29) 27 1070 1230 1350 PP(D-28) 27 937 1200 1530 PP(D-27) 26 989 1150 1270 PP(D-23) 27 1000 1390 1480 Dose 1 PRE(D0) 27 1110 1310 1570 PI(D0 H1.5) 27 943 1240 1520 PI(D0 H6) 27 912 1130 1390 PI(D0 H12) 27 1000 1260 1530 PI(D0 H18) 14 1310 1400 1650 PI(D1) 26 1120 1360 1600 PI(D2) 27 1010 1300 1600 PI(D7) 27 1040 1250 1390 Dose 2 PI(D30) 27 937 1180 1340 PII(D30 H1.5) 27 1030 1250 1400 PII(D30 H3) 26 979 1095 1410 PII(D30 H6) 26 954 1245 1590 PII(D30 H9) 27 999 1190 1470 PII(D30 H12) 25 916 1100 1330 PII(D30 H18) 14 1090 1220 1290 PII(D31) 27 1090 1250 1400 PII(D32) 27 1080 1350 1580 PII(D33) 27 1190 1390 1600 PII(D37) 27 1110 1220 1480 S1Alum Placebo PRE(D-30) 26 1100 1170 1600 PP(D-30 H1.5) 26 896 1190 1300 PP(D-30 H3) 26 1060 1175 1310 PP(D-30 H6) 26 1110 1245 1490 PP(D-30 H9) 26 944 1145 1400 PP(D-30 H12) 25 997 1160 1480 PP(D-30 H18) 11 1140 1390 1710 PP(D-29) 26 1020 1170 1450 PP(D-28) 26 951 1140 1340 PP(D-27) 26 911 1060 1360 PP(D-23) 26 1000 1145 1350
Dose 1 PRE(D0) 26 1030 1260 1520 PI(D0 H1.5) 25 951 1240 1340 PI(D0 H6) 26 989 1130 1310 PI(D0 H12) 26 1030 1265 1520 PI(D0 H18) 11 1220 1400 1560 PI(D1) 25 1100 1270 1630 PI(D2) 25 1010 1230 1390 PI(D7) 26 1010 1240 1420 Dose 2 PI(D30) 25 937 1010 1210 PII(D30 H1.5) 25 1020 1090 1330 PII(D30 H3) 24 824.5 1085 1250 PII(D30 H6) 24 936 1065 1350 PII(D30 H9) 24 820 1075 1295 PII(D30 H12) 25 852 1040 1170 PII(D30 H18) 11 1000 1260 1340 PII(D31) 25 912 1090 1330 PII(D32) 25 1010 1260 1560 PII(D33) 25 1090 1280 1600 PII(D37) 25 1010 1210 1340 MIG S1AS Placebo PRE(D-30) 27 354 513 682 PP(D-30 H1.5) 27 344 392 575 PP(D-30 H3) 27 347 439 558 PP(D-30 H6) 27 320 500 614 PP(D-30 H9) 27 313 452 610 PP(D-30 H12) 27 344 460 623 PP(D-30 H18) 14 373 420 636 PP(D-29) 27 327 528 695 PP(D-28) 27 336 468 568 PP(D-27) 26 349 429.5 542 PP(D-23) 27 337 391 524 Dose 1 PRE(D0) 27 328 496 705 PI(D0 H1.5) 27 385 423 535 PI(D0 H6) 27 332 459 567 PI(D0 H12) 27 361 478 614 PI(D0 H18) 14 443 571 684 PI(D1) 26 441 526 678 PI(D2) 27 435 546 593 PI(D7) 27 384 475 582 Dose 2 PI(D30) 27 393 475 768 PII(D30 H1.5) 27 361 421 856 PII(D30 H3) 26 313 378.5 513 PII(D30 H6) 26 320 375 505 PII(D30 H9) 27 384 424 621 PII(D30 H12) 25 398 499 872 PII(D30 H18) 14 373 565.5 791 PII(D31) 27 604 763 1260 PII(D32) 27 667 850 1070 PII(D33) 27 586 796 908 PII(D37) 27 398 447 535 S1Alum Placebo PRE(D-30) 26 285 435 674 PP(D-30 H1.5) 26 269 336 487 PP(D-30 H3) 26 285 343 504 PP(D-30 H6) 26 313 378 566 PP(D-30 H9) 26 244 327 528 PP(D-30 H12) 25 341 412 564 PP(D-30 H18) 11 340 458 811
PP(D-29) 26 352 418.5 721 PP(D-28) 26 292 397 587 PP(D-27) 26 300 403.5 635 PP(D-23) 26 286 375.5 625 Dose 1 PRE(D0) 26 303 462.5 701 PI(D0 H1.5) 25 308 378 522 PI(D0 H6) 26 302 372.5 557 PI(D0 H12) 26 296 410 588 PI(D0 H18) 11 367 473 722 PI(D1) 25 299 425 606 PI(D2) 25 255 364 620 PI(D7) 26 304 436.5 687 Dose 2 PI(D30) 25 281 452 691 PII(D30 H1.5) 25 269 367 575 PII(D30 H3) 24 237 358 650.5 PII(D30 H6) 24 239 387.5 671 PII(D30 H9) 24 300 350 620 PII(D30 H12) 25 290 377 689 PII(D30 H18) 11 300 442 633 PII(D31) 25 308 427 597 PII(D32) 25 320 410 581 PII(D33) 25 456 537 722 PII(D37) 25 284 364 472 MIP-1 alpha S1AS Placebo PRE(D-30) 27 18 20 25 PP(D-30 H1.5) 27 18 18 21 PP(D-30 H3) 27 18 18 21 PP(D-30 H6) 27 18 18 21 PP(D-30 H9) 27 18 18 22 PP(D-30 H12) 27 18 18 21 PP(D-30 H18) 14 18 18 26 PP(D-29) 27 18 19 24 PP(D-28) 27 18 18 21 PP(D-27) 26 18 18 23 PP(D-23) 27 18 18 22 Dose 1 PRE(D0) 27 18 18 23 PI(D0 H1.5) 27 18 18 22 PI(D0 H6) 27 18 18 21 PI(D0 H12) 27 18 18 21 PI(D0 H18) 14 18 18 20 PI(D1) 26 18 18 22 PI(D2) 27 18 18 22 PI(D7) 27 18 18 26 Dose 2 PI(D30) 27 18 18 21 PII(D30 H1.5) 27 18 18 22 PII(D30 H3) 26 18 18 20 PII(D30 H6) 26 18 18 19 PII(D30 H9) 27 18 18 19 PII(D30 H12) 25 18 18 20 PII(D30 H18) 14 18 18 23 PII(D31) 27 18 18 21 PII(D32) 27 18 18 19 PII(D33) 27 18 22 24 PII(D37) 27 18 18 23 S1Alum Placebo PRE(D-30) 26 18 20 24 PP(D-30 H1.5) 26 18 18 19 PP(D-30 H3) 26 18 18 21
PP(D-30 H6) 26 18 18 19 PP(D-30 H9) 26 18 18 18 PP(D-30 H12) 25 18 18 21 PP(D-30 H18) 11 18 18 23 PP(D-29) 26 18 18 21 PP(D-28) 26 18 18 18 PP(D-27) 26 18 18 19 PP(D-23) 26 18 18 19 Dose 1 PRE(D0) 26 18 18 19 PI(D0 H1.5) 25 18 18 19 PI(D0 H6) 26 18 18 19 PI(D0 H12) 26 18 18 19 PI(D0 H18) 11 18 18 18 PI(D1) 25 18 18 20 PI(D2) 25 18 18 21 PI(D7) 26 18 18 22 Dose 2 PI(D30) 25 18 18 18 PII(D30 H1.5) 25 18 18 20 PII(D30 H3) 24 18 18 18.5 PII(D30 H6) 24 18 18 18 PII(D30 H9) 24 18 18 18 PII(D30 H12) 25 18 18 18 PII(D30 H18) 11 18 18 23 PII(D31) 25 18 18 18 PII(D32) 25 18 18 23 PII(D33) 25 18 19 22 PII(D37) 25 18 18 19 MIP-1 beta S1AS Placebo PRE(D-30) 27 162 190 228 PP(D-30 H1.5) 27 108 141 191 PP(D-30 H3) 27 120 163 199 PP(D-30 H6) 27 140 166 215 PP(D-30 H9) 27 111 131 185 PP(D-30 H12) 27 120 159 179 PP(D-30 H18) 14 136 143.5 182 PP(D-29) 27 124 169 219 PP(D-28) 27 141 174 227 PP(D-27) 26 117 165 196 PP(D-23) 27 128 165 199 Dose 1 PRE(D0) 27 121 164 198 PI(D0 H1.5) 27 132 164 194 PI(D0 H6) 27 129 165 181 PI(D0 H12) 27 142 183 212 PI(D0 H18) 14 200 258 303 PI(D1) 26 234 282.5 408 PI(D2) 27 160 200 265 PI(D7) 27 142 171 243 Dose 2 PI(D30) 27 141 175 240 PII(D30 H1.5) 27 132 164 196 PII(D30 H3) 26 135 153 220 PII(D30 H6) 26 128 177.5 225 PII(D30 H9) 27 120 167 220 PII(D30 H12) 25 162 191 238 PII(D30 H18) 14 228 283.5 327 PII(D31) 27 301 383 540 PII(D32) 27 222 268 307 PII(D33) 27 175 241 279