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: November 12, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Tuberculosis
HIV Infections
Biological: AERAS-402
Biological: Placebo Control
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:
  • The primary objective of this study is to assess the effect of AERAS-402 on the CD4+ lymphocyte count in HIV infected, BCG vaccinated adult subjects with no evidence of active tuberculosis (TB disease). [ Time Frame: CD4+ lymphocyte counts measured 28 days post vaccinations, then at study day 84 and again at 6 month intervals after the initial vaccination. Adverse events will be assessed for 28 days post vaccinations. ] [ Designated as safety issue: Yes ]

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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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
Last Updated: November 12, 2012
Health Authority: South Africa: Medicines Control Council

Keywords provided by Aeras:
HIV
Tuberculosis
Vaccine

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

ClinicalTrials.gov processed this record on September 30, 2014