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

This is a Phase II double-blinded, 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/mm^3.

This study consists of 900 adult subjects (ages 21-45 years of age inclusive) who will receive study vaccine or control at study days 0 and 28.

Further study details as provided by Aeras Global Tuberculosis Vaccine Foundation.

• Tuberculosis
• HIV Infections

• Biological: AERAS-402
  AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA that expresses a fusion protein created from the sequences of three Mycobacterium tuberculosis (Mtb) antigens: 85A, 85B and TB10.4. Dosage will contain 3.0 x 10^10 vp per 0.5mL.
• Biological: Placebo Control
  Placebo will be supplied in vials containing extractable 1.0 mL sterile buffer containing 10 mmol/mL Tris Buffer, 1 mmol/mL MgCl2, 75 mmol/mL NaCl, 5% w/v sucrose, 0.02% w/v polysorbate-80, Water, 0.1 mmol/mL EDTA, 10 mmol/mL l-histidine, 0.5% v/v ethanol. This is the identical buffer solution in which AERAS-402 is formulated.

• Placebo Comparator: Buffer
  A maximum of 450 subjects will receive placebo vaccine that does not contain any AERAS-402.
  Intervention: Biological: Placebo Control
• Experimental: Investigational Vaccine
  A maximum of 450 subjects will receive active vaccine that contains 3 x 10^10 vp / 0.5mL AERAS-402.
  Intervention: Biological: AERAS-402

Inclusion Criteria:

• Is age 21 years through 45 years (i.e., subject has not yet reached his/her 46th birthday at day of randomization)
• Has completed the written informed consent process prior to undergoing any screening evaluations
• Had BCG vaccination at least 5 years ago, documented by medical history or presence of scar
• Females: Ability to avoid pregnancy during the trial: Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) must avoid pregnancy from 28 days prior to administration of the study vaccine through the end of the study. Acceptable methods of avoiding pregnancy include 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.
• Males: Willingness to avoid pregnancy in female sexual partners during the trial. Acceptable methods of avoiding pregnancy include a sterile subject or sexual partner, sexual abstinence (not engaging in sexual intercourse), or use of two forms of acceptable contraception one of which must be the use of a condom.
• Is able to carry out activities of daily living independently
• Has Body Mass Index (BMI) of at least 19 (wt./ht.2) by nomogram
• Has ability to complete follow-up period as required by the protocol
• Is able and willing to commit to avoiding elective surgery for the duration of the study
• Is able and willing to stay in contact with the study site for the duration of the study
• Has committed to simultaneous enrollment in Aeras Vaccine Development Registry Protocol.
• Has 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)
• Has four (4) (for Group 1) or three (3) (for Groups 2-4) 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 Groups 2-4) CD4+ lymphocyte count results greater than 350 cells / mm3.
• Not currently receiving antiretroviral drugs.
• Commits 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 are 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 adenovector-based vaccine
• Medical history that may compromise the evaluation of safety of the subject in the study (e.g., diabetes, seizure disorder, sickle cell disease)
• Pregnant or breastfeeding female, or intending to become pregnant during the study period
• 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 is permitted).