Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in HIV-Infected Adults (C-030-485)
This is a phase II, proof of concept, randomized, double-blind, placebo-controlled study to evaluate the protective efficacy against TB disease, safety, and immunogenicity of MVA85A/AERAS-485 in healthy, HIV-infected adults.
This study consists of 650 adults subjects (ages 18-50 years of age inclusive) who will receive study vaccine or placebo at Study Day 0 and again 6-9 months later. Samples for real-time evaluation of immunogenicity were to be collected from 70 subjects (immunogenicity analysis set).
|Tuberculosis HIV Infections||Biological: MVA85A/AERAS-485 Biological: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Phase II, Proof of Concept, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Protective Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in Healthy, HIV-infected Adults|
- Percentage of Participants With Adverse Events [ Time Frame: Adverse Events (AEs) are recorded for 28 days post vaccination, Serious Adverse Events (SAEs) for at least 6 months post second vaccination. ]The primary objective of this study is to evaluate the safety of MVA85A/AERAS-485 compared to placebo in HIV-infected, African adult subjects without active TB disease.
- Number of TB Cases [ Time Frame: For at least 6 months post second vaccination up to 33 months total follow-up. ]Efficacy of MVA85A/AERAS-485 in the prevention of TB disease compared to control subjects who received placebo in HIV-infected, African adult subjects without active TB disease.
- CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in Anti-retroviral Therapy Negative (ART -)Subjects [ Time Frame: Up to 6 months post second vaccination. ]
- CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART+ Subjects [ Time Frame: Up to 6 months post second vaccination. ]
- HIV-1 Viral Load Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART - Participants [ Time Frame: Up to 6 months post second vaccination. ]
- HIV-1 Viral Load Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART+ Participants. [ Time Frame: Up tp 6 months post second vaccination ]
- Counts of Spot-forming Units After Stimulation With AG85A Peptide Pool. [ Time Frame: 28 days post second vaccination. ]Immunogenicity of MVA85A/AERAS-485 compared to placebo as described by the ex vivo interferon (IFN)-γ enzyme linked immunospot (ELISpot).
- Immunogenicity of MVA85A/AERAS-485 Compared to Placebo as Described by Flow Cytometric Intracellular Cytokine Staining (ICS) of CD4+ and CD8+ T Cells After Stimulation With a Peptide Pool of Mycobacterial Antigens. [ Time Frame: 7 days post second vaccination. ]The antigen-specific negative control-subtracted response for any cytokine (Interferon gamma [INFγ] , Interleukin 2 [IL2], Interleukin 17 [IL17] and tumor necrosis factor [TNF]).
- QuantiFERON (QFN) Conversion Rate in MVA85A/AERAS-485 Recipients Compared to Control Subjects Without a Diagnosis of Tuberculosis During the Trial. [ Time Frame: For at least 6 months post second vaccination up to 33 months total follow-up. ]
|Study Start Date:||July 2011|
|Study Completion Date:||September 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
The placebo is a licensed product manufactured by Allermed, Inc. and is used for evaluation of delayed-type of hypersensitivity reactions in adults.
Subjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo.
MVA85A/AERAS-485 is a recombinant modified vaccinia virus Ankara expressing the M. tuberculosis antigen, Ag85A. Dosage of the study vaccine to be administered will be 1x10^8 pfu.
Subjects received intradermal injection of MVA85A/AERAS-485 on Study Day 0, followed 6-9 months later by a booster injection of MVA85A/AERAS-485.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01151189
|Hopital Aristide Le Dantec|
|Dakar, Senegal, 7325|
|University of Cape Town|
|Cape Town, South Africa, 7925|
|Principal Investigator:||Souleymane Mboup||Hopital Aristide Le Dantec|
|Principal Investigator:||Robert Wilkinson||University of Cape Town|
|Study Director:||Bernard Landry||Aeras|