Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons
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|ClinicalTrials.gov Identifier: NCT03803605|
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : February 15, 2019
Adult participants (18-64 years old) with HIV-1 Infection on ART with a CD4 T cell count ≥ 350 cells/mm3 and viral suppression for ≥ 24 months will be enrolled on this study. Participants will receive two series of combination therapy consisting of one (1) intravenous (IV) dose of VRC-HIVMAB075-00-AB (VRC07-523LS) followed by 10 oral (PO) doses of Vorinostat (VOR) taken every 72 hours. Each series will last approximately 1 month and the two series will be separated by at least one month. Combination ART is (cART) maintained throughout the study. Participants will be on this study for approximately 36 weeks (or about 9 months).
The purpose of this study is to:
- Evaluate the safety of two series of a VRC07-523LS infusion followed by multiple oral doses of VOR
- Determine if combining VRC07-523LS and VOR can have an impact on non-active HIV virus.
|Condition or disease||Intervention/treatment||Phase|
|HIV-1 Infection||Biological: VRC07-523LS Drug: Vorinostat (VOR)||Phase 1|
This is a phase I, single-site, open-label study to evaluate the effects of VOR given in combination with VRC07-523LS on persistent HIV-1 Infection in HIV-infected individuals suppressed on ART.
The investigators hypothesize that combination therapy with VRC07-523LS and VOR will be safe and well-tolerated by HIV-1-infected participants suppressed on ART.
In Step 1, all participants will undergo study screening and enrollment. Participants will complete a baseline Leukapheresis (#1) at Visit 2. Participants will be required to demonstrate the following in order to advance to Step 2:
- Baseline measurement of the frequency of resting CD4 T cell infection ≥ 0.3 infectious units per million (IUPM) determined by Quantitative Viral Outgrowth Assay (QVOA) (lower limit of detection is 0.03 IUPM), as a further decrease from this low frequency of infection cannot be definitively measured given the QVOA assay threshold, and
- Exhibit a measurable increase in resting CD4+ T cell-associated HIV RNA (ca-RNA) following ex vivo exposure to VOR (Step 1).
These criteria assure that eligible enrolled participants will have a measurable endpoint, thus decreasing risk of study participation for participants who would not have a measurable outcome.
Participants progressing to Step 2 will receive two (2) doses of VOR 400 mg PO at a 72-hour interval, followed by leukapheresis (#2). If an increase in ca-RNA is observed in-vivo following the paired VOR dose, participants advance to Step 3.
In Steps 3 and 4, participants receive two series of a single VRC07-523LS infusion followed by multiple doses of VOR.
In the first series (Step 3), participants will receive one VRC07-523LS 40 mg/kg infusion (infusion #1) on Day 0 followed by the 1st dose of VOR 400 mg PO taken at home on Day 2. Participants will take VOR 400 mg PO every 72 hours for a total of 10 doses in Step 3.
In the second series (Step 4), participants will receive one VRC07-523LS 40 mg/kg infusion (infusion #2) on Day 60 followed by the 1st (of the 2nd series of VOR) dose of VOR 400 mg PO on Day 62. As in the previous Step, participants will take VOR 400 mg PO every 72 hours for a total of 10 doses.
Step 5 consists of 2 visits. The post-study treatment leukapheresis (#3) will be completed 5 - 8 weeks after the 2nd VRC07-523LS infusion. The End of Study Visit (EOS) will be scheduled to 2 - 4 weeks following the final leukapheresis (#3) visit.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single Arm: All participants will receive combination therapy consisting of VRC07-523LS and Vorinostat.|
|Masking:||None (Open Label)|
|Official Title:||IGHID 11802 - Combination Therapy With the Novel Clearance Modality (VRC07-523LS) and the Latency Reversal Agent (Vorinostat) to Reduce the Frequency of Latent, Resting CD4+ T Cell Infection (The VOR-07 Study)|
|Actual Study Start Date :||February 12, 2019|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||July 2022|
Experimental: VRC07-523LS + Vorinostat (VOR)
Participants will receive two series of combination therapy consisting of one (1) intravenous (IV) dose of VRC-HIVMAB075-00-AB (VRC07-523LS) followed by 10 oral (PO) doses of Vorinostat (VOR) taken every 72 hours.
VRC07-523LS 40 mg/kg administered intravenously per series (total of 2 infusions administered)
Other Name: VRC-HIVMAB075-00-AB
Drug: Vorinostat (VOR)
Vorinostat 400 mg tablet administered orally every 72 hours for 2 doses in Step 2 and 400 mg administered orally every 72 hours for 10 doses per series (A total of 22 400-mg doses administered)
Other Name: Zolinza
- Percent of Participants with a Grade 3 or higher Treatment-Related Adverse Event (AE) [ Time Frame: First day of study treatment through end of study, a total of approximately 36 weeks ]The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 will be used to measure safety where Grade 3 is defined as severe and Grade 4 is defined as potentially life-threatening. Treatment-Related AEs will be assessments that are considered related to study product as possible, probable, or definite as defined in the protocol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03803605
|Contact: JoAnn Kuruc, MSN, RNemail@example.com|
|Contact: Cindy L Gay, MD, MPHfirstname.lastname@example.org|
|United States, North Carolina|
|University of North Carolina Health Care||Recruiting|
|Chapel Hill, North Carolina, United States, 27514|
|Contact: JoAnn Kuruc, MSN, RN 919-966-8533 email@example.com|
|Contact: Cindy L Gay, MD, MPH 919-843-2726 firstname.lastname@example.org|
|Sub-Investigator: David M Margolis, MD|
|Sub-Investigator: Joseph J Eron, Jr., MD|
|Principal Investigator:||Cindy L Gay, MD, MPH||UNC-Chapel Hill|
|Study Director:||David M Margolis, MD||UNC-Chapel Hill|