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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01017536
Recruitment Status : Completed
First Posted : November 20, 2009
Results First Posted : October 13, 2014
Last Update Posted : September 9, 2016
Crucell Holland BV
Information provided by (Responsible Party):

Brief 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.

Condition or disease Intervention/treatment Phase
Tuberculosis HIV Infections Biological: AERAS-402 Biological: Placebo Phase 2

Detailed Description:
Further study details as provided by Aeras.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : December 2009
Actual Primary Completion Date : March 2012
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Thirteen subjects received placebo vaccine that did not contain any AERAS-402.
Biological: Placebo
Placebo was the identical buffer solution in which AERAS-402 is formulated.

Experimental: Investigational Vaccine
Thirteen subjects received active vaccine 3 x 10^10 vp AERAS-402.
Biological: AERAS-402
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.

Primary Outcome Measures :
  1. CD4+ Lymphocyte Count [ Time Frame: CD4+ counts from samples collected on Study days 0 and 182. ]
    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

Secondary Outcome Measures :
  1. 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) [ Time Frame: 6 months (day 182) post Study Day 0 vaccination. ]
  2. Mtb-specific T Cell Response in HIV-infected BCG-vaccinated Adult Subjects With no Evidence of TB Disease [ Time Frame: Study days 28 and 56 ]
    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.

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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01017536

South Africa
Aurum Institute
Klerksdorp, North-West, South Africa, 2570
Sponsors and Collaborators
Crucell Holland BV
Principal Investigator: Gavin Churchyard, MD, PhD Aurum Institute
Study Director: Bernard Landry, MPH Aeras

Additional Information:
Responsible Party: Aeras Identifier: NCT01017536     History of Changes
Other Study ID Numbers: C-017-402
First Posted: November 20, 2009    Key Record Dates
Results First Posted: October 13, 2014
Last Update Posted: September 9, 2016
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Aeras:

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Immunologic Factors
Physiological Effects of Drugs