The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of an antibody (called VRC01) in HIV-infected adults whose HIV was well-controlled with HIV medicines. The study examined whether VRC01 controlled or delayed the return of HIV viremia when the participants' HIV medicines were briefly stopped during the study.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
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.
Alabama CRS
Birmingham, Alabama, United States
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States
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
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.
Time frame: Measured from entry through week 21 (Steps 1 and 2)
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
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.
Time frame: Measured at Weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI
Measured Value of Plasma VRC01 at the Time of Rebound
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.
Time frame: Measured from entry through week 21 (Steps 1 and 2)
Measured Values of VRC01 in Plasma in the First 8 Weeks of the Analytical Treatment Interruption (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.
Time frame: Measured at weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI
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
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.
Time frame: Measured at weeks 1, 2, 3, and 4 of the ATI
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.