Study of AERAS-402 in Healthy Infants

Study Overview
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Brief Summary
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AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.

Detailed Description
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The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations. AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.

Official Title
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A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: AERAS-402 1.5 x 10^10 vp
* Biological: AERAS-402 3.0 x 10^10 vp
* Biological: AERAS-402 1.0 x 10^11 vp
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent/legal guardian has completed the written informed consent process Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0 Has general good health, confirmed by medical history and physical examination Is up to date on all Expanded Program of Immunization (EPI) immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0 Has ability to complete follow-up period of 728 days as required by the protocol Parent/legal guardian is able and willing to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol Had BCG vaccination ≥ 3 months prior to randomization documented by medical card Exclusion Criteria: Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted) Received immunoglobulin or blood products within 45 days before entry into the study Ever received any investigational drug therapy or investigational vaccine History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection History of allergic disease or reactions to any component of the study vaccine Previous medical history that may compromise the safety of the participant in the study Evidence of a new acute illness that may compromise the safety of the participant in the study Inability to discontinue daily medications during the study History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, e.g., including masses between the leg and abdomen (e.g., inguinal hernia or lymphadenopathy) History or evidence of active tuberculosis A positive QuantiFERON®-TB Gold In-Tube test A household contact with active TB disease

Ages Eligible for Study
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Minimum Age: 112 Days
Maximum Age: 182 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dose Finding Gr 1 placebo x 2<br>Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28. | Biological: Placebo<br> <br> |
| Experimental: Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2<br>Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28. | Biological: AERAS-402 1.5 x 10^10 vp<br> <br> |
| Experimental: Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2<br>Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28. | Biological: AERAS-402 3.0 x 10^10 vp<br> <br> |
| Experimental: Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2<br>Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28. | Biological: AERAS-402 1.0 x 10^11 vp<br> <br> |
| Experimental: Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3<br>Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280. | Biological: AERAS-402 1.5 x 10^10 vp<br> <br> |
| Placebo Comparator: Expanded Safety Phase Gr 5 Placebo x3<br>Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280. | Biological: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Collected Per Subject | Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile | Up to 24 months post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects | To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric ICS of CD4 and CD8 T cells producing any of three cytokines (IFN-γ, TNF-α, and/or IL-2) alone or in combination after stimulation with a peptide pool of mycobacterial peptides. Dimethylsulfoxide (DMSO) subtracted responses are presented. | 28 days post last vaccination | 
| Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay | To evaluate the immunogenicity of AERAS-402 compared to controls. ELISpot assay of specific T cell responses after stimulation with a peptide pool of mycobacterial peptides. Values presented have been corrected for background readings. | 28 days post last vaccination | 
| Antigen-specific Antibody Response - Mean Optical Density (Mean OD) | To evaluate the immunogenicity of AERAS-402 compared to controls by ELISA Assay for Antigen-specific Antibody Response. Median responses of individual Mean OD (absorbance at 450nm) by study group is presented. Higher OD values suggests the presence of antibody to each of the Mtb antigens (Ag85A, Ag85B and TB10.4). | 28 day post last vaccination | 
| Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination | To evaluate the proportion of on-study QuantiFERON conversions from negative to positive in infants that received AERAS-402 compared to controls. A QFT value of on >= 0.35IU/mL was considered positive for this study. | up to 24 months post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Vaccine, Immunogenicity, Prevention of Tuberculosis