Safety and Therapeutic Efficacy of mAb VRC01 During ATI in Early Treatment During Acute HIV Infection

• Status: Completed
• Trial end date: 2019-09-01
• Target enrollment: 24
• Participant gender: All

Summary

This is a placebo-controlled clinical trial of VRC01 administration and analytic treatment interruption (ATI) in adults who began antiretroviral therapy (ART) during early acute HIV infection (Fiebig stage I to III). Eligible volunteers will be randomized in a 3:1 ratio to either VRC01 or placebo, with randomization stratified by Fiebig stage. Volunteers who are receiving ART with a non-nucleoside reverse transcriptase inhibitor (NNRTI) will undergo 4 weeks of protease inhibitor (PI) substitution for their NNRTI prior to randomization. ATI will begin the day of the first dose of either VRC01 or placebo. Participants will be monitored closely for HIV viremia and other pre-defined criteria for ART resumption. Administration of the study agent (VRC01) every three weeks will be discontinued after 24 weeks or if ART is resumed, whichever occurs first. Volunteers who remain virally suppressed without laboratory or clinical indication for ART resumption at 24 weeks will continue intensive monitoring for ART resumption criteria for an additional 24 weeks, during which time no VRC01 or placebo will be administered.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nittaya Phanuphak, MD, PhD
• Treatments: Antibodies, Monoclonal

Criteria

Inclusion Criteria:

• Able and willing to provide written informed consent or, in the case of illiteracy, witnessed verbal informed consent with documentation of a thumbprint in lieu of a signature.

• Passes Test of Understanding

• Man or woman aged 20-50 years.

• Initiated on ART during acute HIV infection (Fiebig Stage I to III at RV 254 enrollment).

• Prescribed ART for at least 24 months prior to enrollment.

• HIV-1 RNA < 50 copies/mL on at least three consecutive measurements within the past 12 months.

• Integrated HIV DNA in PBMCs below the level of detection (1 copy/105 PBMCs) within 6 months prior to enrollment.

• Last documented peripheral blood CD4 >400 cells/mm3 within 3 months prior to enrollment.

• No HIV-related or AIDS-defining illness within 6 months prior to enrollment.

• In general good health

• Able to participate in study visits.

Female-specific Criteria:

• Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman is sexually active and has no history of hysterectomy or tubal ligation or menopause, she must agree to use a prescription birth control method or a barrier birth control method.

• Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for any women unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy

Exclusion Criteria:

• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.

• Ongoing AIDS-related opportunistic infection (including oral thrush).

• Active injection drug use within previous 12 months.

• History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.

• History of chronic urticaria requiring daily treatment.

• Physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, or focal neurologic deficit.

• Hypertension that is not well controlled by medication.

• Hepatitis B surface antigen positive at any time in the past.

• Hepatitis C antibody positive at any time in the past.

• Untreated syphilis

• Estimated GFR < 50 ml/min within the past 90 days.

• Pregnant or breast-feeding.

• Receipt of licensed vaccine or other investigational study agent within 28 days prior to enrollment or past participation in an investigational HIV vaccine study with receipt of active product.

• Current or planned participation in another interventional clinical trial during the study period.

• Chronic or recurrent use of medications that modify host immune response, e.g., oral or parenteral steroids, cancer chemotherapy.

• Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.

• Study site employee.