VRC-HIVMAB060-00-AB (VRC01) in People With Chronic HIV Infection Undergoing Analytical Treatment Interruption

Phase 1

Completed

Conditions: HIV

Interventions: Biological: VRC-HIVMAB060-00-AB (VRC01)

Registration Number: NCT02471326

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: Background:

- A combination of daily drugs (called cART) can keep human immunodeficiency virus (HIV) very low for a long time. But cART can lose effectiveness and cause permanent side effects. If treatment stops, HIV levels go up again. Researchers want to see if a new product can control HIV levels when a person is off cART.

Objective:

- To see if the new product VRC01 is safe and can control the HIV level in the blood when a person is not taking cART.

Eligibility:

- Adults ages 18-65 with HIV who are willing to interrupt their treatment for at least 24 weeks.

Design:

* Participants will be screened with:

* Physical exam

* Medical history

* Heart tests

* Blood and urine tests.

* Their HIV drugs may be switched. They will keep taking them until a few days after Visit 1.

* Visit 1: Repeat screening procedures.

* Participants will also have genetic testing and leukapheresis. For this, blood will be removed through a needle in one arm and circulated through a machine that removes white blood cells. The rest of the blood is returned through a needle in the other arm.

* They will get the first study drug dose through a thin tube in an arm vein for about 1 hour.

* For 24 weeks, participants will have 16 visits. They will have blood drawn every visit. At some visits they will repeat the screening procedures and get another VRC01 dose. They may have another leukapheresis.

* Four weeks after the last dose, participants will restart their cART. For 20 weeks, they will have monthly visits to repeat the screening procedures and discuss new symptoms.

Detailed Description: Recent advances in antibody cloning technologies have led to the discovery of a number of highly potent, HIV-specific, broadly neutralizing monoclonal antibodies from B cells of HIV-infected individuals. It has been shown that certain broadly neutralizing HIV-specific antibodies can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in Simian Immunodeficiency virus (SIV)-infected animals and block cell-to-cell transmission of laboratory-adapted HIV in vitro. However, it is unclear what in vivo effects these antibodies might have on plasma viral rebound in HIV-infected individuals following discontinuation of combination antiretroviral therapy (cART).

In this regard, it has been shown that virtually all infected individuals who initiated cART during the chronic phase of infection experience plasma viral rebound upon cessation of therapy. Current research on the treatment of HIV-infected individuals has been heavily focused on developing strategies aimed at achieving sustained virologic remission in the absence of cART. Thus, it is of great interest to investigate whether a potent HIV-specific monoclonal antibody, such as VRC01, can prevent plasma viral rebound in infected individuals upon discontinuation of cART. We propose to examine the effect of VRC01 on plasma viral rebound in HIV-infected individuals following analytical treatment interruption (ATI).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HIV Positive Subjects	VRC-HIVMAB060-00-AB (VRC01)	VRC-HIVMAB060-00-AB (VRC01) given in HIV-infected Adults (age 18-65 years) on cART with suppressed viremia

Primary Outcome Measures

Name	Time	Method
Number of Grade 3 or Higher Adverse Events	From the start of the initial infusion until up to 48 weeks.	The primary endpoint was the number of grade 3 or higher adverse events, including serious adverse events, that were possibly related to VRC-HIVMAB060-00-AB (VRCO1).

Secondary Outcome Measures

Name	Time	Method
Subjects Who Met Criteria to Restart Antiretroviral Therapy	From Day 3 post initial infusion until up to 28 weeks.	The secondary endpoint was the number of subjects who met protocol defined virologic (sustained HIV RNA \>1000 copies/mL by Abbott HIV RTPCR at 2 consecutive visits), immunologic (a confirmed \>30% decline in CD4 cell count or an absolute CD4 cell count \< 350 cells/mm3), or clinical criteria (HIV-related symptoms) to discontinue VRC01 infusions and restart Antiretroviral Therapy (ART).