A Phase 1 Trial to Evaluate CAP256V2LS in Healthy Adults

Design:

This open-label study evaluated CAP256V2LS (VRC-HIVMAB0102-00-AB) in healthy adults. The primary hypothesis was that subcutaneous (SC) and intravenous (IV) administrations of CAP256V2LS will be safe and well-tolerated in healthy adults. A secondary hypothesis was that CAP256V2LS will be detectable in human sera with a definable half-life.

Study Product:

The CAP256V2LS broadly neutralizing monoclonal antibody (bNAb) targets the V1V2 region of the HIV-1 envelope, is human in origin, and contains two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve antibody half-life in vivo. This bNAb was developed by the VRC/NIAID/NIH in collaboration with The Centre for the AIDS Programme of Research in South Africa (CAPRISA) and is manufactured under current Good Manufacturing Practice (cGMP) regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick. MD. The CAP256V2LS drug product is supplied at a concentration of 100 mg/mL in a sterile, aqueous, buffered solution of 6.25 mL in single-use 10 mL glass vials. R-Gene10 was added as a stabilizing agent to IV doses of CAP256V2LS. R-Gene10 (Arginine Hydrochloride Injection, USP) for intravenous infusion contains L-Arginine Hydrochloride, USP in Water for Injection (equivalent to a 10% solution).

Participants:

Healthy participants, 18-60 years of age

Study Plan:

This open-label study included 2 dosing regimens with CAP256V2LS administered at 5 mg/kg IV and 5 mg/kg SC. A single dose of the study product was administered on Day 0 as shown below.

VRC 611 Study Design

• Group 1

• Study Product: CAP256V2LS
• Participants per Group: 5
• Dose (mg/kg) and Route Administered on Day 0: 5 mg/kg IV
• Group 2

• Study Product: CAP256V2LS
• Participants per Group: 5
• Dose (mg/kg) and Route Administered on Day 0: 5 mg/kg SC

Total Participants: 10

Duration:

Study participation was approximately 24 weeks from the Day 0 product administration.

• INCLUSION CRITERIA:

A volunteer must have met all of the following criteria to be included:

• Able and willing to complete the informed consent process
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
• Available for clinical follow-up through the last study visit
• 18 to 60 years of age
• Based on medical history and physical examination, in good health and without clinically significant findings within 84 days prior to enrollment.
• Weight less than or equal to 115 kg
• Willing to have blood samples collected, stored indefinitely, and used for research purposes

Laboratory Criteria within 84 days prior to enrollment:

• White Blood Cell (WBC) 2,500-12,000/mm^3
• WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval
• Platelets = 125,000-500,000/mm^3
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval
• Creatinine less than or equal to 1.1 x upper limit of normal (ULN) based on the institutional normal range
• Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN based on the institutional normal range
• Negative for HIV infection by an FDA approved method of detection

Criteria Specific to Women of Childbearing Potential:

• Negative beta-human chorionic gonadotropin (HCG) pregnancy test (urine or serum) on day of enrollment, and prior to product administration
• Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the duration of study participation

Exclusion criteria

A volunteer was excluded if one or more of the following conditions applied:

• Woman who is breast-feeding or planning to become pregnant during study participation
• Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study
• Hypertension that is not well controlled
• Receipt of any investigational study product within 28 days prior to enrollment. Note: SARS-CoV-2 vaccines approved by emergency use authorization are not exclusionary.
• Receipt of any live attenuated vaccines within 28 days prior to enrollment.
• Receipt of any vaccine within 2 weeks prior to enrollment/product administration
• Prior receipt of a licensed or investigational monoclonal antibody
• Prior receipt of an HIV vaccine
• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.