A Phase II Trial to Assess Extended Safety and Tolerability of Subcutaneous CAP256V2LS and VRC07-523LS in HIV- Negative Women

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

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

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

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