Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in HIV-Infected Adults (C-030-485)

NCT01151189 | Completed Phase 2 Results DMC

• 1 other identifier: C-030-485
• Study Type: interventional
• Target: 650
• Locations: 2 countries
• Sites: 2

Brief Summary

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).

Conditions

Tuberculosis; HIV Infections

Keywords

HIV; Tuberculosis; Vaccine

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events

  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.

  Adverse Events (AEs) are recorded for 28 days post vaccination, Serious Adverse Events (SAEs) for at least 6 months post second vaccination.

Secondary Outcomes (8)

• Number of TB Cases

  For at least 6 months post second vaccination up to 33 months total follow-up.

• CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in Anti-retroviral Therapy Negative (ART -)Subjects

  Up to 6 months post second vaccination.

• CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART+ Subjects

  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

  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.

  Up tp 6 months post second vaccination

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The placebo is a licensed product manufactured by Allermed, Inc. and is used for evaluation of delayed-type of hypersensitivity reactions in adults.

Biological: Placebo

MVA85A/AERAS-485

EXPERIMENTAL

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.

Biological: MVA85A/AERAS-485

Interventions

MVA85A/AERAS-485 BIOLOGICAL

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.

MVA85A/AERAS-485

Placebo BIOLOGICAL

Subjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo.

Also known as: Candida albicans Skin Test Antigen, Candin

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Has completed the written informed consent process prior to undergoing any screening evaluations.
• Either males or females aged 18-50 years (inclusive) on Study Day 0
• In general good health, confirmed by medical history and physical examination
• Has ability to complete follow-up period as required by the 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, polymerase chain reaction (PCR), or rapid ELISA) diagnosed prior to randomization
• Is willing to allow the investigators to discuss the subject's medical history with the subject's HIV physician
• Has 2 CD4+ lymphocyte count test results \>350 cells/mm3, performed at least 4 weeks apart, one performed within 6 months prior to randomization and one within 30 days prior to randomization
• Has either: a) a negative QuantiFERON-TB Gold In-Tube test result and tuberculin purified protein derivative (PPD) skin test ≤5 mm induration within 30 days prior to randomization or; b) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test \>5 mm and has completed 6 months of isoniazid preventive therapy prior to randomization or; c) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test \>5 mm and has completed treatment for TB disease within 3 year prior to randomization
• 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) in sexual relationships with men must avoid pregnancy by using an acceptable method of avoiding 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), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the use of a condom or a diaphragm combined with spermicide.
• Has completed the written informed consent process for simultaneous enrollment in Aeras Vaccine Development Registry protocol

You may not qualify if:

• Acute illness
• Fever (temperature \> 37.5°C)
• Significant symptomatic infection
• Any evidence of active tuberculosis (TB) disease, as determined by any clinical, radiological, or microbiology measurements.
• Any AIDS defining illness by WHO criteria
• Has received antiretroviral therapy (ART) in the two months prior to study entry (women who have received ART as part of the Prevention of Mother-to-Child Transmission \[PMTCT\] program and completed this more than 2 months prior to randomization ARE eligible)
• Use of any investigational or non-registered drug, vaccine or medical device other than the study vaccine within 182 days preceding dosing of study vaccine, or planned use during the study period
• Previous receipt of a recombinant modified vaccinia Ankara (MVA) or fusion protein (FP) vector at any time.
• Is enrolled in any other clinical product trial
• Administration of methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (for corticosteroids, this will mean prednisolone, or equivalent, ≥0.5 mg/kg/day; inhaled and topical steroids are allowed) and other immunosuppressive therapies, or blood products or blood derivatives within the six months prior to randomization
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
• Presence of any history of cancer \[except basal cell carcinoma of the skin and cervical carcinoma in situ\], or renal failure
• Evidence of severe depression, schizophrenia or mania
• Pregnant females and females who are breast-feeding
• Any history of anaphylaxis in reaction to vaccination

Sponsors & Collaborators

• Aeras: lead
• University of Oxford: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (2)

Hopital Aristide Le Dantec

Dakar, 7325, Senegal

Location

University of Cape Town

Cape Town, 7925, South Africa

Location

Related Publications (1)

• Ndiaye BP, Thienemann F, Ota M, Landry BS, Camara M, Dieye S, Dieye TN, Esmail H, Goliath R, Huygen K, January V, Ndiaye I, Oni T, Raine M, Romano M, Satti I, Sutton S, Thiam A, Wilkinson KA, Mboup S, Wilkinson RJ, McShane H; MVA85A 030 trial investigators. Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2015 Mar;3(3):190-200. doi: 10.1016/S2213-2600(15)00037-5. Epub 2015 Feb 26.

  PMID: 25726088 BACKGROUND

MeSH Terms

Conditions

Tuberculosis; HIV Infections

Interventions

MVA 85A

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Product Director; Bernard Landry
• Organization: Aeras

blandry@aeras.org

301-547-2919

Study Officials

• Souleymane Mboup

  Hopital Aristide Le Dantec

  PRINCIPAL INVESTIGATOR

• Robert Wilkinson

  University of Cape Town

  PRINCIPAL INVESTIGATOR

• Bernard Landry

  Aeras

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2010
• First Posted: June 28, 2010
• Study Start: July 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 24, 2016
• Results First Posted: August 26, 2015

Record last verified: 2016-04

Locations

SE (1); ZA (1)