Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions

Phase 1

Terminated

• Conditions: HIV
• Interventions: Biological: VRC-HIVMAB060-00-AB (VRC01); Biological: Normal Saline Placebo; Biological: 10-1074

• Registration Number: NCT03831945
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Background:

A daily drug combination can keep human immunodeficiency virus (HIV) levels low for a long time. But if this combination antiretroviral therapy (ART) stops, HIV levels go back up. People can also develop resistance or permanent side effects. Researchers want to see if 2 new drugs can help control HIV when a person is not on ART.

Objective:

To see if VRC01 and 10-1074 are safe and control HIV when a person is not on ART.

Eligibility:

Adults 18-65 with HIV

Design:

All participants must agree to practice safer sex. Those who can get pregnant will have a pregnancy test every visit.

Participants will be screened with:

Physical exam

Medicine review

Blood and urine tests

Some participants may need to change their HIV medicine for a brief period of time during the study.

A few weeks later, participants will repeat screening tests and stop taking their HIV medicines.

Interruption phase 1: Participants will have blood tests every 2 weeks, and repeat screening tests every 4 weeks.

Treatment phase: Once their HIV reaches a certain level in the blood, participants will get the 2 study drugs or a salt water placebo. They will not know which they get. Each substance will be given through a thin tube in an arm vein for about 1 hour. Participants will restart their HIV medicines and repeat screening tests every 4 weeks.

Interruption phase 2: Once the level of HIV in the blood becomes undetectable for 3 months, participants will again stop taking their HIV medicines and have blood tests every 2 weeks to monitor the level of HIV in the blood.

Participants will restart their medicines by week 24. They will start sooner if they have certain symptoms or blood levels of HIV become too high. They will repeat most screening tests 3 times over 24 weeks.

Detailed Description

Recent advances in antibody cloning technologies have led to the development of a number of highly potent and human immunodeficiency virus (HIV)-specific broadly neutralizing monoclonal antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in simian/human immunodeficiency virus (SHIV)-infected animals. Preliminary data from clinical trials indicates that bNAbs may delay plasma viral rebound following interruption of antiretroviral therapy (ART) and block cell-to-cell transmission of laboratory-adapted HIV in vitro.

In the above studies, suppression of plasma viremia was dependent on maintaining neutralizing serum levels of bNAbs via repeated intravenous (IV) infusions. A recent pre-clinical study in an acute SHIV-macaque model suggests a limited course of passive immunotherapy with two bNAbs (10-1074 and 3BNC117) given shortly after infection, can result in prolonged suppression of plasma viremia that is not dependent on the continuous presence of the bNAbs18. Based on CD8+ T cell depletion studies, it appears that the prolonged suppression of plasma viremia observed in these animals resulted from the induction of potent antiviral CD8+ T cell immunity by the short course bNAb treatment. The mechanism by which bNAb therapy could induce such a response is unclear but could involve the early formation of unique bNAb-SHIV immune complexes that subsequently induce an effective and durable T cell response to the virus.

In light of these encouraging preclinical outcomes, it is of considerable interest to investigate whether treatment with a single infusion of two bNAbs (VRC01 and 10-1074) which target different epitopes of HIV gp120 (CD4 binding site and V3 glycan, respectively), during transient plasma viremia can induce long-lasting anti-HIV immunity capable of controlling plasma viremia in the absence of ART.

Study Timeline

• Study First Submitted: 2019-02-05
• Study First Submitted QC: 2019-02-05
• Study First Posted: 2019-02-06
• Study Start: 2019-04-04
• Primary Completion: 2020-12-08
• Study Completion: 2020-12-08
• Status Verified: 2021-08
• Results First Submitted: 2021-08-02
• Results First Submitted QC: 2021-09-22
• Last Update Submitted: 2021-09-22
• Results First Posted: 2021-10-12
• Last Update Posted: 2021-10-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single infusion of VRC01 and 10-1074	10-1074	Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is \>/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.
Single infusion of VRC01 and 10-1074	VRC-HIVMAB060-00-AB (VRC01)	Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is \>/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.
Single infusion of Normal Saline	Normal Saline Placebo	Single infusion of 100 mL and 250 mL of normal saline when viral load is \>/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.

Primary Outcome Measures

Name	Time	Method
Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART	From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks	Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 \[a confirmed \>30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (\>40 copies/mL); a sustained (\>4weeks) HIV RNA level of \> 1000 copies/mL, or any HIV related symptoms or pregnancy.\]

Secondary Outcome Measures

Name	Time	Method
Percent of Participants With Grade 3 or Higher Related Adverse Events	From the start of the initial infusion through follow-up phase week 24	Percent of participants with grade 3 or higher adverse events, including serious adverse events, that were probably or definitely related to study agent

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States