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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01151189
• Other study ID #: C-030-485
• Status: Completed
• Phase: Phase 2
• First received: June 24, 2010
• Last updated: July 29, 2015
• Start date: July 2011
• Est. completion date: September 2014

Study information

• Verified date: July 2015
• Source: Aeras
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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).

Description:

This Phase II multi-country trial was conducted as a randomized, double-blind, placebo-controlled trial in 650 HIV-positive adults with no evidence of active TB disease. Subjects were stratified at the time of randomization by whether or not they were receiving anti-retroviral therapy (ART) and then randomized in a ratio of 1:1 to receive either MVA85A/AERAS-485 at 1 x 10^8 plaque forming units (pfu) or placebo (Candin). Randomization of each group was capped so that at least 50% of the subjects randomized were receiving ART at randomization. Subjects were to receive an intradermal injection of MVA85A/AERAS-485 or placebo on Study Day 0, followed 6-9 months later by a booster injection of MVA85A/AERAS-485 or placebo. The minimum follow-up period for each subject was 6 months after their last vaccination, during which subjects were followed for safety, clinical signs and symptoms of TB, and immunogenicity. All subjects were to continue to be followed every 3 months until the last subject enrolled had been followed for 6 months after their last vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 650
• Est. completion date: September 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Principal investigator assessment of lack of willingness to participate and comply with the protocol, or increase in the participant's risk of adverse outcome

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Biological:
• MVA85A/AERAS-485
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.
• Placebo
Subjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo.

Locations

Country	Name	City	State
Senegal	Hopital Aristide Le Dantec	Dakar
South Africa	University of Cape Town	Cape Town

Sponsors (3)

Lead Sponsor	Collaborator
Aeras	European and Developing Countries Clinical Trials Partnership (EDCTP), University of Oxford

Countries where clinical trial is conducted

Senegal,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	Number of TB Cases	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.	For at least 6 months post second vaccination up to 33 months total follow-up.	No
Secondary	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.	Yes
Secondary	CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART+ Subjects		Up to 6 months post second vaccination.	Yes
Secondary	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.	Yes
Secondary	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	Yes
Secondary	Counts of Spot-forming Units After Stimulation With AG85A Peptide Pool.	Immunogenicity of MVA85A/AERAS-485 compared to placebo as described by the ex vivo interferon (IFN)-? enzyme linked immunospot (ELISpot).	28 days post second vaccination.	No
Secondary	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.	The antigen-specific negative control-subtracted response for any cytokine (Interferon gamma [INF?] , Interleukin 2 [IL2], Interleukin 17 [IL17] and tumor necrosis factor [TNF]).	7 days post second vaccination.	No
Secondary	QuantiFERON (QFN) Conversion Rate in MVA85A/AERAS-485 Recipients Compared to Control Subjects Without a Diagnosis of Tuberculosis During the Trial.		For at least 6 months post second vaccination up to 33 months total follow-up.	No