To Assess Extended Safety and Tolerability of Subcutaneous CAP256V2LS and VRC07-523LS Monoclonal Antibodies in HIV-negative Women
Conditions
Keywords
HIV Prevention, broadly neutralising antibodies
Brief summary
A double blinded, Randomized, Placebo- controlled phase II trial to assess extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS in HIV- negative women
Detailed description
STUDY SCHEMA Purpose: To assess extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS monoclonal antibodies in HIV-negative women Study design: A double blinded, randomized, placebo-controlled phase II trial Rationale : Current pharmacokinetic data on CAP256V2LS and VRC07.523LS suggest that plasma antibody concentrations projected out to 120 days and 180 days are above 1 μg/ml. In the macaque model, all animals were protected from challenge at CAP256-VRC26.25-LS plasma concentrations as low as \<0.75 μg/ml. CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose. In the absence of a plasma antibody concentration that correlates with protection in humans, this dose-ranging phase II trial will assess safety of CAP256V2LS and VRC07.523LS administered at 4-monthly and 6-monthly dosing intervals, using antibody concentrations and breakthrough HIV infections, if any to guide dose and dosing interval selections for the future phase III trial. Study participants: HIV negative (N=984) 18 to 30 years. Study sites: * CAPRISA eThekwini Clinical Research Site, Durban, KwaZulu-Natal, South Africa * CAPRISA Vulindlela Clinical Research Site, Howick, KwaZulu-Natal, South Africa * The Centre for Infectious Disease Research in Zambia (CIDRZ): Matero Clinical Research Site, Lusaka, Zambia Study duration : Enrolment will take place within 56 days of screening. * Participants will receive study product at 24-week (6-monthly) or 16-week (4-monthly) intervals. * Depending on the dosing interval, participants will continue in follow up until approximately 16, 18 or 20 months. Study products: CAP256V2LS and VRC07-523LS administered as separate injections Primary objective: * To evaluate the safety of CAP256V2LS and VRC07-523LS in HIV-negative women Secondary objectives: * To evaluate the tolerability of CAP256V2LS and VRC07-523LS * To assess the PK profile of study products administered 16 weekly (4 monthly) in comparison to 24 weekly (6 monthly) administration * To compare HIV incidence rates in antibody and placebo recipients * To assess CAP256V2LS and VRC07-523LS systemic and mucosal concentrations in relation to breakthrough infections * To determine the prevalence of autoantibody induction * To assess participant acceptability of the subcutaneous injections
Interventions
BIOLOGICALBroad band monoclonal antibodies named as CAP256V2LS and VRC07- 523LS
HIV prevention
Sponsors
Centre for Infectious Disease Research in Zambia
European and Developing Countries Clinical Trials Partnership (EDCTP)
Medical Research Council, South Africa
University of Cape Town
Amsterdam Institute for Global Health and Development
Centre for the AIDS Programme of Research in South Africa
National Institute of Communicable Diseases - NICD
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Masking description
HIVNegative women age-18 to 30 years
Intervention model description
Current pharmacokinetic data on CAP256V2LS and VRC07.523LS suggest that plasma antibody concentrations projected out to 120 days and 180 days are above 1 μg/ml. In the macaque model, all animals were protected from challenge at CAP256-VRC26.25-LS plasma concentrations as low as \<0.75 μg/ml. CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose. In the absence of a plasma antibody concentration that correlates with protection in humans, this dose-ranging phase II trial will assess safety of CAP256V2LS and VRC07.523LS administered at 4-monthly and 6-monthly dosing intervals, using antibody concentrations and breakthrough HIV infections, if any to guide dose and dosing interval selections for the future phase III trial.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 30 years of age Persons born Female (assigned female sex at birth) and identifying as female.Able and willing to complete the informed consent process * Able to understand the information provided including the potential impact and/or risks linked to SC administration of the study product, willing to comply with protocol procedures, has access to the clinical research site and is available for follow-up for the study duration * Based on clinical assessment, participant must be in good general health as per opinion of the Principal Investigator (PI) or designee * Haemoglobin \> 10g/dl * Creatinine ≤ 1.25 x ULN * ALT \< 1.25 x ULN * HIV negative * Negative β-HCG (human chorionic gonadotropin) pregnancy test on day of enrolment * If of reproductive potential, has evidence of effective contraceptive use and is willing to adhere to effective contraceptive use during the study period * Sexually active in the last 3 months
Exclusion criteria
* Any significant acute or chronic medical condition, situation or circumstance that in the opinion of the PI/designee makes the participant unsuitable for participation in the study, or jeopardises the safety or rights of the participant * If planning a pregnancy for the duration of the study, currently pregnant or breastfeeding * A history of alcohol or substance use judged by the PI to potentially interfere with participant study compliance * Prior participation in an investigational HIV vaccine trial, except if proof of allocation to the placebo arm is available. * Receipt of any vaccines within 28 days prior to enrolment * Administration of a monoclonal antibody or polyclonal immunoglobulin within 6 months prior to enrolment * Investigational HIV-related products received within 6 months prior to enrolment * Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or angioedema * Evidence of autoimmune disease or currently receiving immunosuppressive therapy * Current participation in any other research studies that would interfere with the objectives of this study. The determination of whether participation in another study would be exclusionary for a given participant will be made by the PI/designee
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with any grade 3 or higher reactogenicity events within the first 3 days and adverse events after administration of CAP256V2LS in combination with VRC07-523LS | 18 months | The aim of the CAPRISA 012C trial is to assess extended safety and obtain an estimate of efficacy in preventing HIV infection in young women by measuring * Proportion of participants with any grade 3 or higher reactogenicity events within the first 3 days after administration of CAP256V2LS in combination with VRC07-523LS * Proportion of participants with any grade 3 or higher adverse events related to the administration of CAP256V2LS in combination with VRC07-523LS |
Countries
Zambia
Outcome results
None listed