TuberculosisPhase 2NCT01151189
Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in HIV-Infected Adults (C-030-485)
A Phase 2 study testing MVA85A/AERAS-485 in people with Tuberculosis and HIV Infections, run by Aeras at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Tuberculosis, HIV Infections
- What is being tested?
- MVA85A/AERAS-485
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 650 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jul 2011to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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).
Read the detailed 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.
- Conditions
- Tuberculosis, HIV Infections
- Being tested
- MVA85A/AERAS-485, Placebo
- Keywords
- HIV, Tuberculosis, Vaccine
- Medical subject headings
- Tuberculosis, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVA85A/AERAS-485Biological
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.
PlaceboBiological
Also called Candida albicans Skin Test Antigen, Candin
Subjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: MVA85A/AERAS-485 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Measured: Up to 6 months post second vaccination.
CD4+ Lymphocyte Counts Before and After Administration of MVA85A/AERAS-485 Compared to Placebo in ART+ Subjects
Measured: 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
Measured: 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.
Measured: Up tp 6 months post second vaccination
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)-γ enzyme linked immunospot (ELISpot).
Measured: 28 days post second vaccination.
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 [INFγ] , Interleukin 2 [IL2], Interleukin 17 [IL17] and tumor necrosis factor [TNF]).
Measured: 7 days post second vaccination.
QuantiFERON (QFN) Conversion Rate in MVA85A/AERAS-485 Recipients Compared to Control Subjects Without a Diagnosis of Tuberculosis During the Trial.
Measured: For at least 6 months post second vaccination up to 33 months total follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2010 (estimated)
- Study startJul 2011
- Primary completionMay 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 650 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- Souleymane Mboup, Principal investigator, Hopital Aristide Le DantecRobert Wilkinson, Principal investigator, University of Cape TownBernard Landry, Study director, Aeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01151189
- Sponsor's protocol ID
- C-030-485
- Status last verified
- Apr 2016
- First submitted
- 24 Jun 2010
- Last updated
- 24 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25726088
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01151189
- Acronym / sponsor ID
- C-030-485
- Conditions
- Tuberculosis, HIV Infections
- Keywords
- HIV, Tuberculosis, Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 650 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- University of Oxford, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- Jul 2011
- Primary completion
- May 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 28 Jun 2010 (estimated)
- Results
- Posted 26 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboThe placebo is a licensed product manufactured by Allermed, Inc. and is used for evaluation of delayed-type of hypersensitivity reactions in adults. |
| MVA85A/AERAS-485 | Experimental | Biological: MVA85A/AERAS-485MVA85A/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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MVA85A/AERAS-485Subjects received intradermal injection of MVA85A/AERAS-485 on Study Day 0, followed 6-9 months later by a booster injection of MVA85A/AERAS-485. | Biological | MVA85A/AERAS-485 |
| PlaceboAlso: Candida albicans Skin Test Antigen, CandinSubjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo. | Biological | Placebo |
Primary outcome
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.
8 secondary outcomes
Number of TB Cases
Time frame: 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
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 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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25726088Ndiaye 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Souleymane Mboup principal investigator
Hopital Aristide Le Dantec
Robert Wilkinson principal investigator
University of Cape Town
Bernard Landry study director
Aeras
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MVA85A/AERAS-485 in people with Tuberculosis and HIV Infections, run by Aeras at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Senegal, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01151189, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2016.