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VRC 601: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to HIV-Infected...

Phase 1
Completed
Conditions
Viral Load
HIV Antibodies
Neutralizing Antibody
HIV-1 Infection
Monoclonal Antibody
Interventions
Biological: VRC-HIVMAB060-00-AB
Registration Number
NCT01950325
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

This is the first clinical trial of the VRC-HIVMAB060-00-AB (VRC01) monoclonal antibody. VRC01 is a broadly neutralizing antibody directed against HIV. This is a dose-escalation study to examine safety, tolerability, dose and pharmacokinetics of VRC01. The hypothesis is that VRC01 will be safe for administration to HIV-1 infected adults by the intravenous (IV) and subcutaneous (SC) routes and will not elicit hypersensitivity reactions. Samples will be collected to learn if VRC01 is detectable in mucosal secretions and blood of participants and how long VRC01 can be detected in the blood after it is given.

Between 15 and 25 HIV-1 infected adults, ages 18-70 years will be enrolled. There are 4 dose escalation groups for IV administration; the doses are 1 mg/kg, 5 mg/kg, 20 mg/kg and 40 mg/kg. There is 1 group for SC administration at 5 mg/kg. Each group is expected to include at least 3 participants. Each participant will receive two infusions of VRC01 with about 1 month between doses. Infusions are administered in an inpatient unit and an overnight stay at the NIH Clinical Center is required. No more than one subject per day per group will receive a first infusion of the VRC01 product by the IV route and no more than one subject per week will receive a first infusion of the product by the SC route. Study participation lasts for 24 weeks. Participant health and effect on CD4 count and HIV viral load will be monitored. Samples will be collected and stored for research purposes.

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Detailed Description

This is the first clinical trial of the VRC-HIVMAB060-00-AB (VRC01) monoclonal antibody. VRC01 is a broadly neutralizing antibody directed against HIV. This is a dose-escalation study to examine safety, tolerability, dose and pharmacokinetics of VRC01. The hypothesis is that VRC 01 will be safe for administration to HIV-1- infected adults by the intravenous (IV) and subcutaneous (SC) routes and will not elicit hypersensitivity reactions. Samples will be collected to learn if VRC01 is detectable in mucosal secretions and blood of participants and how long VRC01 can be detected in the blood after it is given.

Up to 30 HIV-1 infected adults will be enrolled. Adult 18-60 years old will participate in the dose escalation part of the study. There are 4 dose escalation groups for IV administration; the doses are 1 mg/kg, 5 mg/kg, 20 mg/kg and 40 mg/kg. There is 1 group for SC administration at 5 mg/kg. Each dose escalation group is expected to include at least 3 participants. Each participant during the dose escalation part of the study will receive two infusions of VRC01 with about 1 month between doses, with infusions administered in an inpatient unit and an overnight stay at the NIH Clinical Center required. No more than one subject per day per group will receive a first infusion of the VRC01 product by the IV route and no more than one subject per week will receive a first infusion of the product by the SC route. Study participation lasts for 24 weeks for participants who receive two doses. After the dose escalation is completed, about 10 HIV-infected adults, ages 18-70 years old, with detectable viral load will be enrolled to receive one dose of VRC01 at 40 mg/kg IV with follow-up for 12 weeks. Participant health and effect on CD4 count and HIV viral load will be monitored. Samples will be collected and stored for research purposes.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
27
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 2 or Group 3VRC-HIVMAB060-00-AB5 mg/kg IV (Group 2) or 5 mg/kg SC (Group 3)\[only portion of the study that is randomized\]
Group 4VRC-HIVMAB060-00-AB20 mg/kg IV
Group 1VRC-HIVMAB060-00-AB1mg/kg IV
Group 5VRC-HIVMAB060-00-AB40 mg/kg IV
Primary Outcome Measures
NameTimeMethod
Serious adverse events and new chronic medical conditions requiring ongoing medical managementFrom first product admin thru Study Week 24
Adverse events of all severitiesFrom first product admin thru 56 days after last admin
Solicited systemic adverse eventsFor 3 days after ea product admin
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics at each dose levelThru 4 weeks after first dose and thru 8 wks after second dose
Assess whether anti-drug antibody can be detected in study agent recipientsFrom first product admin thru Study Week 24

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

🇺🇸

Bethesda, Maryland, United States

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