A Phase 1 Trial to Evaluate CAP256V2LS in Healthy Adults

Study Overview
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Brief Summary
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Background: HIV is a serious disease with no cure or vaccine to prevent it. Using antibodies could be a way to prevent HIV infection. Antibodies are made by the human body to fight germs. Researchers want to test an antibody, CAP256V2LS. Objective: To test CAP256V2LS to see if it is safe and how the body responds to it. Eligibility: Healthy people, ages 18-60 Design: Participants were screened with a medical history, physical exam, and blood tests. Some females had a pregnancy test. Participants were assigned to one of two groups. Based on their group, they got 1 dose of CAP256V2LS in 1 of 2 ways: Some participants got CAP256V2LS as an infusion. A thin tube was placed in an arm vein and CAP256V2LS was given into the vein using a pump. Some participants got CAP256V2LS injected under the skin. A small needle was used to inject CAP256V2LS into the fatty tissue of the belly, arm, or thigh. They got 1 to 4 injections. On the day they got CAP256V2LS, participants gave blood samples at different time points. Participants were asked to check their temperature every day for 7 days after receiving CAP256V2LS. They used a tool to measure any redness, swelling, or bruising they may have at the site where they received the study drug. Participants had visits at least 2-3 times during the first week after they got CAP256V2LS. Then they had about 9 more visits over the next 6 months. Visits included blood tests.

Detailed Description
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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.

Official Title
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VRC 611: A Phase 1 Safety and Pharmacokinetic Study to Evaluate a Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2LS) Administered Via Subcutaneous and Intravenous Injection in Healthy Adults

Conditions
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HIV

Intervention / Treatment
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* Biological: VRC-HIVMAB0102-00-AB


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: CAP256V2LS (5 mg/kg IV)<br>CAP256V2LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) | Biological: VRC-HIVMAB0102-00-AB<br>* The VRC-HIVMAB0102-00-AB (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.<br>* Other names: CAP256V2LS;|
| Experimental: Group 2: CAP256V2LS (5 mg/kg SC)<br>CAP256V2LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) | Biological: VRC-HIVMAB0102-00-AB<br>* The VRC-HIVMAB0102-00-AB (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.<br>* Other names: CAP256V2LS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration | Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Local Symptom is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. | 7 days after CAP256V2LS product administration, at approximately Week 1 | 
| Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration | Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. | 7 days after CAP256V2LS product administration, at approximately Week 1 | 
| Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following CAP256V2LS Product Administration | Unsolicited adverse event (AE) data collection included AEs of all severities from the date of product administration through the Day 28 post-product administration visit. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management (reported as a separate outcome) were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity. | Day 0 through 4 weeks after CAP256V2LS Product Administration | 
| Number of Participants With Serious Adverse Events (SAEs) Following CAP256V2LS Product Administration | SAEs were recorded from receipt of study product administration through the last expected study visit at Week 24. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity. | Day 0 after CAP256V2LS product administration through the study participation, up to Week 24 | 
| Number of Participants With New Chronic Medical Conditions Following CAP256V2LS Product Administration | New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 24. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity. | Day 0 after CAP256V2LS product administration through the study participation, up to Week 24 | 
| Number of Participants With Abnormal Laboratory Measures of Safety Following CAP256V2LS Product Administration | Abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV) platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete Blood Count (CBC) with differential and Chemistry (ALT and creatinine) results were collected at different timepoints throughout the study per the protocol's schedule of evaluations. Comprehensive metabolic panel (CMP) was collected at baseline, and 2 weeks after product administration and as needed at additional timepoints. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used. | Day 0 through 4 weeks after CAP256V2LS Product Administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameters of CAP256V2LS: Maximum Observed Serum Concentration (Cmax) | Serum concentrations of CAP256V2LS by dose group following a single administration. Cmax is the peak serum concentration that CAP256V2LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group. | Baseline through 24 weeks after CAP256V2LS product administration | 
| Pharmacokinetic (PK) Parameters of CAP256V2LS: Time to Reach Maximum Observed Serum Concentration (Tmax) | Tmax is the time it takes to reach Cmax of CAP256V2LS after it has been administered; it is determined based on the summary PK curve for each dose group. | Baseline through 24 weeks after CAP256V2LS product administration | 
| Pharmacokinetic (PK) Parameters of CAP256V2LS: Beta Half-life (T1/2b) | Beta half-life (T1/2b) is the time required for half of the CAP256V2LS product to be eliminated from the serum. | Baseline through 24 weeks after CAP256V2LS product administration | 
| Pharmacokinetic (PK) Parameters of CAP256V2LS: Clearance (CL) Following IV Administration | Clearance is the rate of CAP256V2LS elimination divided by the plasma CAP256V2LS concentration; determined based on the summary pharmacokinetic (PK) curve for the IV study group. | Baseline through 24 weeks after CAP256V2LS product administration | 
| Pharmacokinetic (PK) Parameters of CAP256V2LS: Clearance (CL/F) Following SC Administration | Rate of CAP256V2LS elimination divided by the plasma CAP256V2LS concentration; determined based on the summary pharmacokinetic (PK) curve for the SC group. Clearance following a SC administration is calculated as Clearance (CL)/Bioavailability (F). | Baseline through 24 weeks after CAP256V2LS product administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibodies, HIV Prevention, Broadly-Neutralizing Human Monoclonal Antibodies, First in Human, Anti-Drug Antibody Response