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: No masking
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|
- Percentage of Participants Who Experienced a Grade 3 or Higher 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 from entry through week 21 (Steps 1 and 2) ]The primary safety outcome examined the occurrence of a Grade 3 or higher systemic (i.e., not a local reaction) adverse event (AE) possibly, probably, or definitely related to the administration of the VRC01 antibody. The DAIDS AE Grading Table (V2.0) was used.
- Percentage of Participants Who Had a 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 at Weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI ]The primary efficacy outcome is the percentage of participants who had a 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.
- Measured Value of Plasma VRC01 at the Time of Rebound [ Time Frame: Measured from entry through week 21 (Steps 1 and 2) ]Measured value of plasma VRC01, measured in micrograms per milliliter, at the time of rebound. Rebound is defined as the point in time when plasma HIV-1 RNA surpassed 40 copies/mL.
- Measured Values of VRC01 in Plasma in the First 8 Weeks of the Analytical Treatment Interruption (ATI) [ Time Frame: Measured at weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI ]Measured values of plasma VRC01, measured in micrograms per milliliter, through week 8 of the ATI. The median and range of all VRC01 measurements taken in the first 8 weeks of the ATI were reported.
- Percentage of Participants Who Had a 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 at weeks 1, 2, 3, and 4 of the ATI ]The secondary efficacy outcome was the percentage of participants who had a 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.
|Actual Study Start Date:||August 2015|
|Study Completion Date:||October 2016|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Participants received 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 was 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 was well-controlled with antiretroviral therapy (ART). The study examined whether VRC01 delayed or prevented the return of HIV viremia in participants who underwent a brief analytical treatment interruption (ATI).
The study enrolled HIV-infected participants 18 years and older who were on ART (ART was not provided by the study). At a pre-entry study visit, participants underwent blood collection, a leukapheresis procedure, and a rectal biopsy. The study lasted about 34 weeks and proceeded in three stages: Step 1 (approximately 9 weeks), Step 2 (approximately 12 weeks), and Step 3 (approximately 13 weeks).
During Step 1, participants received three doses of VRC01 via intravenous (IV) infusion. The first dose of VRC01 was given on day 0. Seven days after receiving this first dose of VRC01, participants discontinued ART. Participants received the second and third doses of VRC01 at days 21 and 42, respectively. For 7 days after each VRC01 IV infusion, participants monitored and recorded their temperature and any symptoms. In addition to the 3 infusion study visits, participants attended weekly visits from day 7 through approximately day 63 (week 9).
Participants entered Step 2 of the study and resumed ART when they had a confirmed CD4+ T-cell count of less than 350 cells/μL or a confirmed return of HIV-1 viremia, defined per protocol as an HIV-1 RNA measurement of greater than or equal to 200 copies/mL followed by a confirmatory measurement of greater than or equal to 1000 copies/mL or three consecutive HIV-1 RNA measurements of over 200 copies/mL.
Step 2 study visits occurred on the day ART was resumed (Step 2, entry) and every four weeks thereafter (approximately at Step 2, weeks 4, 8, and 12) until a participant's HIV viral load decreased to less than 50 copies/mL.
Throughout the study, visits included clinical assessments and blood collection. Some blood was stored for future testing. Some study visits included the collection of oral, rectal, and (for women) cervical secretion samples. On day 63, participants underwent another leukapheresis procedure and a rectal biopsy.
Participants who completed Step 2 may have optionally entered Step 3 for additional testing. Entry into Step 3 occurred at least 3 months after the participant had completed Step 2. Step 3 participants had 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|