Safety and Immunogenicity of AERAS-402 in HIV-infected, Bacillus Calmette-Guerin (BCG)-Vaccinated Adults

Study Overview
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Brief Summary
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This was a Phase II, randomized, double-blind, placebo-controlled trial conducted at 1 site in South Africa. A total of 26 subjects were randomized 1:1 to receive 2 doses of either AERAS-402 at 3 x 10^10 vp (N=13) or placebo (N=13) on Study Days 0 and 28. Dose-escalation to a second group of 40 subjects was planned, but although no safety concerns were identified, the sponsor decided not to continue the study.

Detailed Description
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Further study details as provided by Aeras.

Official Title
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Phase II Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of AERAS-402 in HIV-infected, BCG-vaccinated Adults With CD4+ Lymphocyte Counts Greater Than 350 Cells/mm3

Conditions
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Tuberculosis, HIV Infections

Intervention / Treatment
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* Biological: AERAS-402
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 years through 45 years (i.e., subject had not yet reached his/her 46th birthday at day of randomization). Had completed the written informed consent process prior to undergoing any screening evaluations. Had BCG vaccination at least 5 years previously, documented by medical history or presence of scar. Females: Ability to avoid pregnancy for at least 6 months after receiving the last study vaccination: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) must have avoided pregnancy from 28 days prior to administration of the study vaccine and must have agreed to avoid pregnancy through at least 6 months after receiving the last study vaccination. Acceptable methods of avoiding pregnancy included a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), or use of a combination of at least two forms of acceptable contraception: hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), and the use of a condom or a diaphragm; or the use of a condom or a diaphragm combined with spermicide. Was able to carry out activities of daily living independently. Had Body Mass Index (BMI) of at least 19 (wt./ht.2) by nomogram. Had ability to complete follow-up period as required by the protocol. Was able and willing to commit to avoiding elective surgery for at least 6 months after receiving the last study vaccination. Was able and willing to stay in contact with the study site for the duration of the study. Had committed to simultaneous enrollment in Aeras Vaccine Development Registry Protocol. Had laboratory evidence of human immunodeficiency virus (HIV) infection, defined as a positive HIV-1 ELISA test plus a positive confirmatory test (e.g., a second HIV-1 ELISA, PCR, or rapid ELISA). Had four (4) (for Group 1) or three (3) (for Group 2)* CD4+ lymphocyte count tests, each performed at least four days apart within the 42-day screening period, with at least three (for Group 1) or two (for Group 2) CD4+ lymphocyte count results greater than 350 cells / mm3. Not currently receiving antiretroviral drugs. Committed to not participate in any other clinical trials during the first 12 months of participation in this study. Exclusion Criteria: Acute illness. Fever ≥37.5°C. Significant symptomatic infection. Used immunosuppressive medication within 42 days prior to randomization (inhaled and topical corticosteroids were permitted). Received immunoglobulin or blood products within 42 days prior to randomization. Received any investigational drug therapy or vaccine within 182 days prior to randomization. History of having received any adenovirus-vector-based vaccine. Medical history that may have compromised the evaluation of safety of the subject in the study (e.g., diabetes, seizure disorder, sickle cell disease). Pregnant or breastfeeding female, or intention to become pregnant during the study within 6 months after receiving the last study vaccination. Liver function tests >Grade 2 per the toxicity table. Currently receiving treatment for TB, or evidence of active TB disease based on history, physical examination, chest X-ray, or laboratory evaluation (INH prophylaxis was permitted).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Placebo<br>Thirteen subjects received placebo vaccine that did not contain any AERAS-402. | Biological: Placebo<br>* Placebo was the identical buffer solution in which AERAS-402 is formulated.<br>|
| Experimental: Investigational Vaccine<br>Thirteen subjects received active vaccine 3 x 10^10 vp AERAS-402. | Biological: AERAS-402<br>* AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA that expresses a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens: 85A, 85B and TB10.4.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ Lymphocyte Count | Assess the effect of AERAS-402 on the CD4+ lymphocyte count after 6 months in HIV-infected, BCG-vaccinated adult subjects with no evidence of active tuberculosis (TB disease) Change in cells/mm^3 pre-vaccination to Study Day 182 | CD4+ counts from samples collected on Study days 0 and 182. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HIV Viral Load in HIV-infected, BCG-vaccinated Adult Subjects Before and After Administration of AERAS-402 (From Day 1 to Day 182) |  | 6 months (day 182) post Study Day 0 vaccination. | 
| Mtb-specific T Cell Response in HIV-infected BCG-vaccinated Adult Subjects With no Evidence of TB Disease | Intracellular cytokine staining (ICS) assay immune response was expressed as the percentage of CD4+ and CD8+ T cells producing any one of three cytokines (IFN-γ, TNF-α, or IL-2) or any combination of the three cytokines simultaneously after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools. | Study days 28 and 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Tuberculosis, Vaccine