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

October 2, 2017 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

An Exploratory, Open-Label Study of VRC-HIVMAB060-00-AB (VRC01) in Subjects With Chronic HIV Infection Undergoing Analytical Treatment Interruption

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA

    1. Age 18-65 years old.
    2. HIV-1 infection and clinically stable.
    3. In general good health and with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
    4. CD4+ cell count >450 cells/mm^3 at screening.

    5. Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for greater than or equal to 3 years. Subjects with blips (i.e., detectable viral levels on cART) prior to screening may be included provided they satisfy the following criteria:

      1. The blips are <400 copies/mL, and
      2. Succeeding viral levels return to levels below the limit of detection on subsequent testing.
    6. Willingness to undergo ATI.

    7. Laboratory values within pre-defined limits at screening:

      1. Absolute neutrophil count >1,000/mm^3.
      2. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women.
      3. Platelet count >100,000/mm^3.
      4. Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of normal (ULN).
      5. Estimated or a measured creatinine clearance rate of greater than or equal to 50 mL/min as determined by the NIH Clinical Center laboratory.
      6. AST and ALT levels of <2.5 x ULN.
    8. Willingness to have samples stored for future research.

Reproductive Risks

Contraception: The effects of VRC01 on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate pregnancy prevention per the investigator. This includes highly reliable established lifestyle of complete abstinence of potentially reproductive sexual activity, or use of BOTH a long term hormonal or barrier (e.g. implant, depot injection, IUD in female participant or female partner of participant) method of contraception that is fully effective prior to dosing, COMBINED WITH a barrier method (male or female condom) for all potentially reproductive sexual activity. Pregnancy prevention must be maintained as effective and practiced continuously for the duration of study participation. Females of childbearing-age must have a negative pregnancy test result prior to receiving VRC01. During the course of the study, if a female participant, or the partner of a male participant suspects or in fact becomes pregnant, the effected participant should inform the study staff immediately, as well as the woman's primary care physician. Subjects must use safe sex practices during the trial, and particularly during the ATI phase, when risk of transmission of HIV may be increased.

  • EXCLUSION CRITERIA

    1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
    2. Documented virologic failure to >1 cART regimen.
    3. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
    4. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.
    5. Receipt of other investigational study agent within 28 days of enrollment.
    6. Any active malignancy that may require systemic chemotherapy or radiation therapy.
    7. Systemic immunosuppressive medications received within 3 months prior to enrollment (Not excluded: corticosteroid nasal spray or inhaler; topical corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur [length of therapy less than or equal to 10 days, with completion in greater than or equal to 30 days prior to enrollment]).

    8. History or other clinical evidence of:

      1. Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction).
      2. Severe illness, malignancy, immunodeficiency other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
    9. Active drug or alcohol use or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.
    10. Breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HIV Positive Subjects
VRC-HIVMAB060-00-AB (VRC01) given in HIV-infected Adults (age 18-65 years) on cART with suppressed viremia
Biological: VRC-HIVMAB060-00-AB (VRC01)
A potent HIV-specific monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Grade 3 or Higher Adverse Events
Time Frame: 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).
From the start of the initial infusion until up to 48 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjects Who Met Criteria to Restart Antiretroviral Therapy
Time Frame: 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).
From Day 3 post initial infusion until up to 28 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 13, 2015

Primary Completion (Actual)

April 7, 2017

Study Completion (Actual)

April 7, 2017

Study Registration Dates

First Submitted

June 12, 2015

First Submitted That Met QC Criteria

June 12, 2015

First Posted (Estimate)

June 15, 2015

Study Record Updates

Last Update Posted (Actual)

October 31, 2017

Last Update Submitted That Met QC Criteria

October 2, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 150140
  • 15-I-0140 (Other Identifier: NIAID IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

NIH Biomedical Translational Research Information System

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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