HIV Clinical Trial
— MVA(TB)029Official title:
Phase II Randomised Controlled Trial to Evaluate Safety and Immunogenicity of MVA85A and Selective, Delayed Bacille Calmette-Guerin (BCG) Vaccination in Infants of HIV Infected Mothers
Verified date | September 2015 |
Source | University of Cape Town |
Contact | n/a |
Is FDA regulated | No |
Health authority | South Africa: Medicines Control Council |
Study type | Interventional |
Rationale: The Bacille Calmette-Guérin (BCG) vaccine protects children against disseminated
tuberculosis (TB) including TB meningitis and miliary TB, but efficacy against pulmonary TB
is inconsistent among children and adults. Administration of live attenuated BCG to infants
known to be HIV infected is contraindicated by the World Health Organization (WHO), due to
the risk of serious vaccine adverse events (BCG disease. Developing countries, which lack
capacity for integration of early infant HIV testing with infant vaccination schedules, have
not fully implemented the WHO guidelines on BCG vaccination of HIV exposed infants. Newborn
infants of HIV infected mothers continue to receive routine BCG before HIV infection has
been excluded.
Clinical trials of new viral-vectored TB vaccines, including MVA85A, a modified vaccinia
virus Ankara (MVA) vaccine expressing the Mycobacterium tuberculosis antigen 85A, have to
date enrolled infants who were already vaccinated with routine BCG at birth. However, TB
vaccination regimens that depend on newborn BCG will remain unsafe for HIV infected infants.
Infants of HIV infected mothers, who constituted 29% of babies born in South Africa in 2009,
would benefit from a new TB vaccination strategy, in which BCG is delayed until after HIV
infection has been excluded. These HIV exposed infants also have greater increased risk of
TB disease. Testing the safety and immunogenicity of MVA85A vaccine prime, followed by
selective delayed BCG boost, in HIV exposed newborns, is a critical step towards delivery of
a new TB vaccine regimen that is safe and effective for all infants, regardless of HIV
exposure.
Study Design: Double blinded, randomised, controlled trial. HIV exposed infants will be
randomised 1:1 to receive single dose, intradermal MVA85A vaccine or Candin® control at
birth. The first 60 infants enrolled in the trial will form a pilot safety cohort for formal
Data Monitoring & Ethics Committee (DMEC) safety review. Thereafter, safety and
immunogenicity outcomes will be measured in all infants.
Study Population: Infants (n=340) born to HIV infected mothers receiving antiretroviral
therapy (ART) or Prevention of Mother to Child Transmission (PMTCT) prophylaxis.
Sites: Worcester (University of Cape Town) and Khayelitsha (Stellenbosch University), South
Africa
Study Intervention: Newborn infants will receive 1 x 108 pfu MVA85A vaccine or Candin®
control by intradermal injection. Infants confirmed HIV uninfected by HIV PCR will receive
BCG Vaccine SSI at 8 weeks of age. Infants confirmed HIV infected by HIV PCR will not
receive BCG.
Primary specific aims:
To evaluate the safety of MVA85A given at birth to HIV exposed uninfected infants.
To evaluate the safety of BCG given at 8 weeks of age to HIV exposed uninfected infants,
using an MVA85A prime and BCG boost strategy.
Secondary specific aims:
To evaluate the immunogenicity of MVA85A given at birth to HIV exposed uninfected infants.
To evaluate the immunogenicity of BCG given at 8 weeks of age to HIV exposed uninfected
infants, using an MVA85A prime and BCG boost strategy.
Safety endpoints:
Local, regional, and systemic adverse events (AEs) and serious adverse events (SAEs).
Immunology endpoints:
Frequencies of CD4 and CD8 T cells producing any of 4 cytokines (IL-17, IFN-γ, TNF-α, or
IL-2), or polyfunctional combinations of these cytokines simultaneously, following
stimulation with antigen Ag85A or BCG, measured by whole blood intracellular cytokine assay
(WB-ICS).
Specific proliferative capacity of CD8 and CD4 T cells that produce any of the three
cytokines (IFN-γ, TNF-α, and/or IL-2) or combinations of these cytokines simultaneously,
measured by a novel whole blood 6-day lymphoproliferative flow cytometric assay (WB-prolif).
Relative proportions and absolute numbers of peripheral blood myeloid and lymphoid cell
subsets, measured directly ex vivo by flow cytometry.
Study groups: The first 60 infants enrolled in Study Group 1 will undergo intensive safety
evaluation, followed by DMEC review of Day-28 safety data. The DMEC will make a formal
recommendation on continuation of enrollment and/or changes to the protocol, based on this
safety review. Study Groups 2-5 will be evaluated for clinical safety and immunology
outcomes.
Statistical Analysis: Cumulative 12-month incidence of local, regional, and systemic AEs, by
category, will be compared for HIV exposed uninfected subjects receiving MVA85A vaccine or
Candin® control at birth. The sample size has 90% probability of detecting an SAE with a
true occurrence rate of 1.5% in infants receiving MVA85A vaccine and 80% power to detect a
15% difference in the rate of non-serious AEs (20% compared to 35%) between the two study
arms (p<0.05). Multivariate models will be built to explore longitudinal immunological data
and identify independent associations with MVA85A vaccination and covariates of interest.
Status | Completed |
Enrollment | 248 |
Est. completion date | May 2015 |
Est. primary completion date | May 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A to 96 Hours |
Eligibility |
Inclusion Criteria: - HIV infected mother receiving either cART, or started on PMTCT prophylaxis - Maternal antenatal and post-natal written informed consent; - Maternal age 18 years or older at the time of informed consent; - Infant age < 96 hours; - Infant birth and residence in the study area; - Mother contactable and able to attend follow-up visits. Exclusion Criteria: - Neonatal Apgar score < 7 at 5 minutes; - Infant birth weight < 2,000g or > 4,500g; - Estimated infant gestational age < 32 weeks; - Neonatal respiratory distress; - History or evidence of infant congenital abnormality, or immunosuppressive condition, other than HIV infection; - Any maternal or infant condition or systemic illness that in the opinion of the investigator is likely to affect safety or immunogenicity of study vaccine; - Infant BCG vaccination prior to enrollment; - Residence in a household, or frequent close contact, with an adult diagnosed with active TB who has not yet completed TB treatment; - Mother with active TB who has not yet completed TB treatment; - Unknown or negative maternal HIV status; - Intention to leave the study area and/or unable to attend follow-up visits. |
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
South Africa | Desmond Tutu TB Centre (DTTC), Stellenbosch University | Khayelitsha | |
South Africa | South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town | Worcester |
Lead Sponsor | Collaborator |
---|---|
Mark Hatherill | Department for International Development, United Kingdom, Medical Research Council, Oxford-Emergent Tuberculosis Consortium, University of Oxford, University of Stellenbosch, Wellcome Trust |
South Africa,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety | Local, regional, and systemic adverse events (AEs) and serious adverse events (SAEs). | 1 year | Yes |
Secondary | Immunogenicity | Frequencies of CD4 and CD8 T cells producing IL-17, IFN-?, TNF-a, or IL-2, or polyfunctional combinations of these cytokines, following stimulation with antigen Ag85A or BCG, measured by whole blood intracellular cytokine assay. Specific proliferative capacity of CD8 and CD4 T cells that produce IFN-?, TNF-a, or IL-2, or combinations of these cytokines, measured by whole blood 6-day lymphoproliferative flow cytometric assay. Relative proportions and absolute numbers of peripheral blood myeloid and lymphoid cell subsets, measured directly ex vivo by flow cytometry. |
1 Year | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06162897 -
Case Management Dyad
|
N/A | |
Completed |
NCT03999411 -
Smartphone Intervention for Smoking Cessation and Improving Adherence to Treatment Among HIV Patients
|
Phase 4 | |
Completed |
NCT02528773 -
Efficacy of ART to Interrupt HIV Transmission Networks
|
||
Active, not recruiting |
NCT05454839 -
Preferences for Services in a Patient's First Six Months on Antiretroviral Therapy for HIV in South Africa
|
||
Recruiting |
NCT05322629 -
Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum Women
|
N/A | |
Completed |
NCT02579135 -
Reducing HIV Risk Among Adolescents: Evaluating Project HEART
|
N/A | |
Active, not recruiting |
NCT01790373 -
Evaluating a Youth-Focused Economic Empowerment Approach to HIV Treatment Adherence
|
N/A | |
Not yet recruiting |
NCT06044792 -
The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
|
||
Completed |
NCT04039217 -
Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM
|
Phase 4 | |
Active, not recruiting |
NCT04519970 -
Clinical Opportunities and Management to Exploit Biktarvy as Asynchronous Connection Key (COMEBACK)
|
N/A | |
Completed |
NCT04124536 -
Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women
|
N/A | |
Recruiting |
NCT05599581 -
Tu'Washindi RCT: Adolescent Girls in Kenya Taking Control of Their Health
|
N/A | |
Active, not recruiting |
NCT04588883 -
Strengthening Families Living With HIV in Kenya
|
N/A | |
Completed |
NCT02758093 -
Speed of Processing Training in Adults With HIV
|
N/A | |
Completed |
NCT02500446 -
Dolutegravir Impact on Residual Replication
|
Phase 4 | |
Completed |
NCT03805451 -
Life Steps for PrEP for Youth
|
N/A | |
Active, not recruiting |
NCT03902431 -
Translating the ABCS Into HIV Care
|
N/A | |
Completed |
NCT00729391 -
Women-Focused HIV Prevention in the Western Cape
|
Phase 2/Phase 3 | |
Recruiting |
NCT05736588 -
Elimisha HPV (Human Papillomavirus)
|
N/A | |
Recruiting |
NCT03589040 -
Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant
|
Phase 2 |