Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-Label Study of the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to HIV-Infected Adults Undergoing a Brief Analytical Treatment Interruption|
- Occurrence of a Grade 3 or greater systemic (i.e., not a local reaction) adverse event (AE) that is possibly, probably, or definitely related to the administration of the VRC01 antibody [ Time Frame: Measured through week 21 ]
- Confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 8 of the analytical treatment interruption (ATI) or indication to re-initiate ART prior to week 8 of the ATI [ Time Frame: Measured through week 8 of the ATI ]
- Measurement of Cmax in the plasma [ Time Frame: Measured through week 21 ]
- Measurement of Cmin in the plasma [ Time Frame: Measured through week 21 ]
- Measurement of AUC (area under the curve) in the plasma [ Time Frame: Measured through week 21 ]
- Confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 4 of the ATI or indication to reinitiate ART prior to week 4 of the ATI [ Time Frame: Measured through week 4 of the ATI ]
|Study Start Date:||July 2015|
|Study Completion Date:||March 2016|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Participants will receive an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42.
40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP.
Administered over about 30 to 60 minutes using a volumetric pump.
Other Name: VRC-HIVMAB060-00-AB
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of a human monoclonal antibody, VRC-HIVMAB060-00-AB (known as VRC01), in HIV-infected adults whose HIV is well-controlled with antiretroviral therapy (ART). The study will examine whether VRC01 delays or prevents the return of HIV viremia in participants who are undergoing a brief analytical treatment interruption (ATI).
The study will enroll HIV-infected participants 18 years and older who are on ART. (ART will not be provided by the study). At a pre-entry study visit, participants will undergo blood collection, a leukapheresis procedure, and a rectal biopsy. The study will last about 34 weeks and proceed in three stages: Step 1 (approximately 9 weeks), Step 2 (approximately 12 weeks), and Step 3 (approximately 13 weeks).
During Step 1, participants will receive three doses of VRC01 via intravenous (IV) infusion. The first dose of VRC01 will be given on day 0. Seven days after receiving this first dose of VRC01, participants will discontinue ART. Participants will receive the second and third doses of VRC01 at days 21 and 42, respectively. For 7 days after each VRC01 IV infusion, participants will monitor and record their temperature and any symptoms. In addition to the 3 injection study visits, participants will attend weekly visits from day 7 through approximately day 63 (week 9).
Participants will enter Step 2 of the study and resume ART when they have a confirmed return of HIV-1 viremia or a confirmed CD4+ T-cell count of less than 350 cells/μL.
Step 2 study visits will occur on the day ART is resumed (Step 2, week 1) and every four weeks thereafter (approximately at Step 2, weeks 4, 8, and 12) until a participant's HIV viral load decreases to less than 50 copies/mL.
Throughout the study, visits will include clinical assessments and blood collection. Some blood will be stored for future testing. Some study visits will include the collection of oral, rectal, and (for women) cervical secretion samples. On day 63, participants will undergo another leukapheresis procedure and a rectal biopsy.
Participants who have completed Step 2 may optionally enter Step 3 for additional testing. Entry into Step 3 will occur at least 3 months after the participant has completed Step 2. Step 3 participants will have additional study visits for a leukapheresis procedure, a rectal biopsy, and clinical follow up.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02463227
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, Pennsylvania|
|Penn Therapeutics, CRS|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Pablo Tebas, MD||University of Pennsylvania|