Clinical trial NCT04408963: A Phase 1 Trial to Evaluate CAP256V2LS in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Keywords: HIV Prevention
Broadly-Neutralizing Human Monoclonal Antibodies
First in Human
Anti-Drug Antibody Response
Antibodies
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2020-06-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: * INCLUSION CRITERIA:

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

1. Able and willing to complete the informed consent process
2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
3. Available for clinical follow-up through the last study visit
4. 18 to 60 years of age
5. Based on medical history and physical examination, in good health and without clinically significant findings within 84 days prior to enrollment.
6. Weight less than or equal to 115 kg
7. Willing to have blood samples collected, stored indefinitely, and used for research purposes

   Laboratory Criteria within 84 days prior to enrollment:
8. White Blood Cell (WBC) 2,500-12,000/mm\^3
9. WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval
10. Platelets = 125,000-500,000/mm\^3
11. Hemoglobin within institutional normal range or accompanied by the PI or designee approval
12. Creatinine less than or equal to 1.1 x upper limit of normal (ULN) based on the institutional normal range
13. Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN based on the institutional normal range
14. Negative for HIV infection by an FDA approved method of detection

    Criteria Specific to Women of Childbearing Potential:
15. Negative beta-human chorionic gonadotropin (HCG) pregnancy test (urine or serum) on day of enrollment, and prior to product administration
16. 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:

1. Woman who is breast-feeding or planning to become pregnant during study participation
2. 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
3. Hypertension that is not well controlled
4. 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.
5. Receipt of any live attenuated vaccines within 28 days prior to enrollment.
6. Receipt of any vaccine within 2 weeks prior to enrollment/product administration
7. Prior receipt of a licensed or investigational monoclonal antibody
8. Prior receipt of an HIV vaccine
9. 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.

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration
timeFrame: 7 days after CAP256V2LS product administration, at approximately Week 1
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of CAP256V2LS Product Administration
timeFrame: 7 days after CAP256V2LS product administration, at approximately Week 1
measure: Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following CAP256V2LS Product Administration
timeFrame: Day 0 through 4 weeks after CAP256V2LS Product Administration
measure: Number of Participants With Serious Adverse Events (SAEs) Following CAP256V2LS Product Administration
timeFrame: Day 0 after CAP256V2LS product administration through the study participation, up to Week 24
measure: Number of Participants With New Chronic Medical Conditions Following CAP256V2LS Product Administration
timeFrame: Day 0 after CAP256V2LS product administration through the study participation, up to Week 24
measure: Number of Participants With Abnormal Laboratory Measures of Safety Following CAP256V2LS Product Administration
timeFrame: Day 0 through 4 weeks after CAP256V2LS Product Administration
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameters of CAP256V2LS: Maximum Observed Serum Concentration (Cmax)
timeFrame: Baseline through 24 weeks after CAP256V2LS product administration
measure: Pharmacokinetic (PK) Parameters of CAP256V2LS: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: Baseline through 24 weeks after CAP256V2LS product administration
measure: Pharmacokinetic (PK) Parameters of CAP256V2LS: Beta Half-life (T1/2b)
timeFrame: Baseline through 24 weeks after CAP256V2LS product administration
measure: Pharmacokinetic (PK) Parameters of CAP256V2LS: Clearance Rate
timeFrame: Baseline through 24 weeks after CAP256V2LS product administration
measure: Pharmacokinetic (PK) Parameters of CAP256V2LS: Volume of Distribution
timeFrame: Baseline through 24 weeks after CAP256V2LS product administration
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Richard L Wu, M.D.
role: PRINCIPAL_INVESTIGATOR
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