Safety and Immunogenicity of AERAS-402 in HIV-infected, Bacillus Calmette-Guerin (BCG)-Vaccinated Adults
Condition: Tuberculosis; HIV Infections
MeSH terms: Tuberculosis
Intervention: AERAS-402; Placebo
Intervention description: 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.; Placebo was the identical buffer solution in which AERAS-402 is formulated.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 21 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: HIV; Tuberculosis; Vaccine

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 21 years through 45 years (i.e., subject had not yet reached his/her 46th birthday
             at day of randomization).

          2. Had completed the written informed consent process prior to undergoing any screening
             evaluations.

          3. Had BCG vaccination at least 5 years previously, documented by medical history or
             presence of scar.

          4. 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.

          5. Was able to carry out activities of daily living independently.

          6. Had Body Mass Index (BMI) of at least 19 (wt./ht.2) by nomogram.

          7. Had ability to complete follow-up period as required by the protocol.

          8. Was able and willing to commit to avoiding elective surgery for at least 6 months
             after receiving the last study vaccination.

          9. Was able and willing to stay in contact with the study site for the duration of the
             study.

         10. Had committed to simultaneous enrollment in Aeras Vaccine Development Registry
             Protocol.

         11. 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).

         12. 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.

         13. Not currently receiving antiretroviral drugs.

         14. Committed to not participate in any other clinical trials during the first 12 months
             of participation in this study.

        Exclusion Criteria:

          1. Acute illness.

          2. Fever ≥37.5°C.

          3. Significant symptomatic infection.

          4. Used immunosuppressive medication within 42 days prior to randomization (inhaled and
             topical corticosteroids were permitted).

          5. Received immunoglobulin or blood products within 42 days prior to randomization.

          6. Received any investigational drug therapy or vaccine within 182 days prior to
             randomization.

          7. History of having received any adenovirus-vector-based vaccine.

          8. Medical history that may have compromised the evaluation of safety of the subject in
             the study (e.g., diabetes, seizure disorder, sickle cell disease).

          9. Pregnant or breastfeeding female, or intention to become pregnant during the study
             within 6 months after receiving the last study vaccination.

         10. Liver function tests >Grade 2 per the toxicity table.

         11. 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).