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

July 25, 2016 updated by: Aeras

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

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.

Study Overview

Status

Completed

Detailed Description

Further study details as provided by Aeras.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • North-West
      • Klerksdorp, North-West, South Africa, 2570
        • Aurum Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Thirteen subjects received placebo vaccine that did not contain any AERAS-402.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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)
Time Frame: 6 months (day 182) post Study Day 0 vaccination.
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
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.
Study days 28 and 56

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Study Director: Bernard Landry, MPH, Aeras
  • Principal Investigator: Gavin Churchyard, MD, PhD, Aurum Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

November 18, 2009

First Submitted That Met QC Criteria

November 18, 2009

First Posted (Estimate)

November 20, 2009

Study Record Updates

Last Update Posted (Estimate)

September 9, 2016

Last Update Submitted That Met QC Criteria

July 25, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Placebo

3
Subscribe