Antibodies are natural proteins that the body makes to fight infections. Antibodies can also be manufactured like a drug and infused or injected into the body to prevent or treat a disease. The purpose of this study is to test the safety of and the body's response to an antibody against HIV in healthy, HIV-uninfected adults.
The purpose of this study is to evaluate the safety, tolerability, and drug levels of five different schedules for the intravenous (IV) and subcutaneous (SC) administration of a human monoclonal antibody (VRC-HIVMAB060-00-AB \[VRC01\]) against HIV in healthy, HIV-uninfected adults. The study will enroll 88 healthy, HIV-uninfected adults aged 18 to 50 years. This study will enroll participants in 5 groups. Groups 1-3 will enroll simultaneously. Groups 1 and 2 will be randomized together but not blinded, while Group 3 will be randomized separately and will be blinded. With the implementation of Version 2.0, Groups 4 and 5 will be randomized together and will enroll simultaneously. Each group will have a different schedule of clinic visits and receive different doses of VRC01 or placebo for VRC01. Participants will attend 8 months of scheduled clinic visits. Participants in Group 1 will receive an IV infusion of VRC01 on Days 0, 28, 56, 84, 112, and 140. Participants in Group 2 will receive an IV infusion of VRC01 on Days 0, 56, and 112. Participants in Group 3 will receive an IV infusion of VRC01 or IV placebo for VRC01 on Day 0, followed by SC injections of VRC01 or SC placebo for VRC01 on Days 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, and 154. Participants in Groups 4 and 5 will receive an IV infusion of VRC01 (each group will receive a different dose) on Days 0, 56, and 112. Participants will remain in the clinic for about an hour after receiving the infusions and injections for observation and monitoring. Participants in Group 3 who have no problems with the first SC injection will have to wait in the clinic for only a half an hour after the rest of the SC injections. At study entry, participants will give a medical history; undergo a physical exam, blood collection, and urine collection; and receive HIV risk reduction counseling. At follow-up visits, participants will undergo a brief physical exam and blood collection, receive HIV risk reduction counseling, and be asked questions about their health and their experience participating in the study. At all visits, participants who were born female will have a pregnancy test. At select study visits, saliva, rectal, and semen or cervical secretion samples will be collected from participants who consent to collection of these samples.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
88
Administered IV in 100 mL of normal saline (Sodium Chloride for Injection 0.9%, USP) or administered SC by needle and syringe injection.
Sterile, buffered aqueous solution of 25 mM Sodium Citrate, 50 mM Sodium Chloride, 150 mM L-Arginine Hydrochloride, 10% Dextran 40, and 0.005% Polysorbate 80 at pH 5.8 administered SC by needle and syringe injection
Sodium Chloride for Injection 0.9%, USP administered IV in 100 mL of normal saline (Sodium Chloride for Injection 0.9%, USP)
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States
Fenway Health (FH) CRS
Boston, Massachusetts, United States
Columbia P&S CRS
New York, New York, United States
New York Blood Center CRS
New York, New York, United States
Assessment of local and systemic reactogenicity signs and symptoms
Assessment occurs at each product administration and for 3 days after administration.
Time frame: Measured through Month 5.5 visit
Measurements of laboratory measures of safety
Time frame: Measured through participants' last study visit at Month 8
Assessment of adverse events
Time frame: Measured through participants' last study visit at Month 8
Assessment of serious adverse events
Time frame: Measured through participants' last study visit at Month 8
Number of early discontinuation of infusions
The assessment will include the reason(s) for discontinuation of infusions and early study termination.
Time frame: Measured through participants' last study visit at Month 8
Serum concentration of VRC01 in Groups 1-3 at Month 6
Time frame: Measured at Month 6
Serum concentration of VRC01 28 and 56 days after each IV administration in Groups 4 and 5
Time frame: Measured 56 days after each IV administration
Magnitude of serum neutralization of a single VRC01 sensitive virus isolate as measured in the TZMbl assay at multiple timepoints
Time frame: Measured through participants' last study visit at Month 8
Serum concentration of VRC01 in each group at multiple timepoints
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Case Clinical Research Site
Cleveland, Ohio, United States
Penn Prevention CRS
Philadelphia, Pennsylvania, United States
Time frame: Measured through participants' last study visit at Month 8
Serum concentration of anti-VRC01 antibodies in each group at multiple timepoints compared to corresponding VRC01 levels
Time frame: Measured through participants' last study visit at Month 8
Mucosal levels of VRC01 in each group at multiple timepoints
Time frame: Measured through participants' last study visit at Month 8
Magnitude of neutralization in genital, rectal, and oral secretions of a single VRC01 sensitive virus isolate as measured in the TZMbl assay at multiple timepoints
Time frame: Measured through participants' last study visit at Month 8
Assessment of VRC01 binding in serum and genital, rectal, and oral secretions to multiple Env proteins in each group at multiple timepoints (assessed by binding antibody multiplex assay)
Time frame: Measured through participants' last study visit at Month 8