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

This study has been completed.
Sponsor:
Collaborator:
Crucell Holland BV
Information provided by (Responsible Party):
Aeras
ClinicalTrials.gov Identifier:
NCT01017536
First received: November 18, 2009
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Tuberculosis
HIV Infections
Biological: AERAS-402
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Aeras:

Primary Outcome Measures:
  • CD4+ Lymphocyte Count [ Time Frame: CD4+ counts from samples collected on Study days 0, 7, 14, 28, 35, 42, 56, 84, and 182. ] [ Designated as safety issue: Yes ]
    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)


Secondary Outcome Measures:
  • HIV Viral Load in HIV-infected, BCG-vaccinated Adult Subjects Before and After Administration of AERAS-402 [ Time Frame: 6 months (day 182) post Study Day 0 vaccination. ] [ Designated as safety issue: Yes ]
  • Mtb-specific T Cell Response in HIV-infected BCG-vaccinated Adult Subjects With no Evidence of TB Disease [ Time Frame: Study days 0, 7, 14, 28, 35, 42, 56, 84, and 182 ] [ Designated as safety issue: No ]
    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. TB10.4 response data are not shown due to minimal response.


Enrollment: 26
Study Start Date: December 2009
Study Completion Date: May 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

Further study details as provided by Aeras.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017536

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

No publications provided

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT01017536     History of Changes
Other Study ID Numbers: C-017-402
Study First Received: November 18, 2009
Results First Received: October 8, 2014
Last Updated: October 8, 2014
Health Authority: South Africa: Medicines Control Council

Keywords provided by Aeras:
HIV
Tuberculosis
Vaccine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycobacterium Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014