Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons
Verified May 2019 by University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party)
University of North Carolina, Chapel Hill
First received: January 10, 2019
Last updated: May 3, 2019
Last Verified: May 2019
History of Changes
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
Biological : VRC07-523LS
Drug : Vorinostat (VOR)
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)
Primary Purpose: Treatment
|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)|
Further study details as provided by University of North Carolina, Chapel Hill:
Primary Outcome Measures
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.
|Study Start Date:||February 12, 2019|
|Estimated Study Completion Date:||July 2022|
|Estimated Primary Completion Date:||July 2022 (Final data collection date for primary outcome measure)|
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
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)
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. Eligibility
|Ages Eligible for Study:||18 Years to 64 Years|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- ≥ 18 years and < 65 years of age
- Ability and willingness of participant to give written informed consent. Note: Due to the lack of foreseeable benefit to study participants, mentally incompetent participants will not be enrolled.
- HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay.
A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
Note: Continuous ART prior to screening is defined as not missing more than 4 total days and never more than 2 consecutive days in the 3 months prior to screening.
a.At least 3 ART agents (not counting ritonavir if less than a 200 mg total daily dose or cobicistat as one of the agents)
NOTE: One of the agents must include an integrase inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a boosted-PI (protease inhibitor).
b.Two ART agents in which one of the agents is either a boosted PI or an integrase inhibitor.
NOTE: Other fully suppressive antiretroviral combinations will be considered on a case-by-case basis.
NOTE: Prior changes in, or elimination of, medications for easier dosing schedule, intolerance, toxicity, improved side effect profile or within a drug class are permitted if an alternative suppressive regimen was maintained but not within 3 months prior to screening.
NOTE: Changes in drug formulation or dose are allowed (e.g., TDF to TAF, ritonavir to cobicistat, or separate ART agent dosing to fixed-dose combination), but none within 30 days prior to screening.
NOTE: The documented plasma HIV-1 RNA must be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
NOTE: Participants with a prior positive TB IGRA and documented evidence of completed prophylaxis treatment may enroll in the study and do not need to undergo IGRA at screening. Participants with a prior positive IGRA who have not completed prophylaxis treatment will be excluded.
- Written or oral documentation communicated by clinician or clinician's staff of one of the following:
a.Physician report/letter b.Operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy in any partner assigned male sex at birth, hysterectomy, oophorectomy, non-surgical permanent sterilization, or tubal ligation.) c.Discharge summary d.Documented or participant-reported absence of a period for ≥ one year must be confirmed with Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory.
- Condoms (male or female) with or without a spermicidal agent b) Diaphragm or cervical cap with spermicide c) Intrauterine device (IUD) d) Tubal ligation e) Hormone-based contraceptive f) Successful vasectomy
NOTE: For female partners who are receiving ritonavir or cobicistat, estrogen-based contraceptives are not reliable and an alternative method should be suggested.
NOTE: Investigational research agent is defined as any unlicensed investigational drug not yet approved by the FDA for intended use in humans.
Hematological: Absolute neutrophil count (ANC) ≥1,500 /mcL; Platelets ≥125,000 / mcL; Hemoglobin ≥ 13 g/dL (male) and ≥ 11 g/dL (females)
Coagulation: Prothrombin Time or INR ≤1.5x upper limit of normal (ULN)
Chemistries: K+ levels - Within normal limits; Mg++ levels ≥ 1.2 mEq/L but <1.5 x ULN; Glucose - Screening serum glucose ≤ Grade 1 (fasting or non- fasting); Albumin ≥ 3.3 g/dL
Renal: Creatinine clearance determined by the CKD-Epi equation
Hepatic: Serum total bilirubin - Total bilirubin < 1.5 X ULN. If total bilirubin is elevated, direct bilirubin must be < 2 times the ULN range.
NOTE: If participant is on an atazanavir-containing therapy, then a direct bilirubin should be measured instead of the total bilirubin and must be ≤ 1.0 mg/dL.; AST (SGOT) and ALT (SGPT) ≤ 1.25 X ULN; Alkaline Phosphatase ≤ 2.0 X ULN; Lipase < 1.6 X ULN; Urinalysis: Urine Protein - Negative or trace allowed ULN = upper limit of normal
NOTE: Co-enrollment in observational only studies is permitted.
NOTE: Co-enrollment in other studies using FDA approved medication that are not otherwise listed as prohibited will be evaluated by the study PI and permitted on a case by case basis.
NOTE: In cases of untreated syphilis, participant may rescreen following documentation of adequate treatment of syphilis
Not Exclusionary:  corticosteroid nasal spray;  inhaled corticosteroids;  topical steroids for mild, uncomplicated dermatitis; or  a single course of oral /parental prednisone or equivalent at doses <2mg/kg/day and length of therapy <11 days with completion at least 30 days prior to enrollment.
Not exclusionary: Persons with mild, stable, and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgement of the site investigator (or designee), is likely not subject to exacerbation and likely not to complicate AE assessments.
NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary with documentation of complete resection at least 3 months prior to enrollment).
Specifically exclusionary:  recent psychosis;  ongoing risk for suicide; or  recent history of suicide attempt or gesture.
a) A process that would affect the immune response b) A process that would require medication that affects the immune response c) Any contraindication to repeated injections, infusions, or blood draws d) A condition or process (e.g., chronic urticarial or recent injection or infusion with evidence of residual inflammation) for which signs and symptoms could be confused with reactions to the study product
Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes)
- If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.
- If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
Note: Elevated BP occurring during research leukapheresis procedures completed within the past 12 months are excluded from this requirement. Other isolated incidences of elevated BP should be reviewed by study PI (or designee) to determine whether they are exclusionary. Acceptable isolated elevations must be noted as acceptable and signed by study PI or designee.
- Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring:
a.Daily steroid or long acting beta-agonist prevention b.Use of high dose inhaled corticosteroids OR c.In the past year has either of the following:
a. >1 exacerbation of symptoms treated with oral/parental corticosteroids; b. Emergency care, urgent care, hospitalization, or intubation for asthma.
b.Sickle cell disease
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03803605
|Contact: JoAnn Kuruc, MSN, RNemail@example.com|
|Contact: Cindy L Gay, MD, MPHfirstname.lastname@example.org|
Locations Show More
|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
Sponsors and CollaboratorsUniversity of North Carolina, Chapel Hill
National Institute of Allergy and Infectious Diseases (NIAID)
|Principal Investigator:||Cindy L Gay, MD, MPH||UNC-Chapel Hill|
|Study Director:||David M Margolis, MD||UNC-Chapel Hill|
|Responsible Party:||University of North Carolina, Chapel Hill|
|ClinicalTrials.gov Identifier:||NCT03803605 History of Changes|
|Other Study ID Numbers:||18-1217|
|Study First Received:||January 10, 2019|
|Last Updated:||May 3, 2019|
|Individual Participant Data|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Keywords provided by University of North Carolina, Chapel Hill:VRC07-523LS
Additional relevant MeSH terms:
ClinicalTrials.gov processed this data on August 16, 2019
This information is provided by ClinicalTrials.gov.