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The Effect of Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01319383
First Posted: March 21, 2011
Last Update Posted: June 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institutes of Health (NIH)
Merck Sharp & Dohme Corp.
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
Results First Submitted: February 9, 2017  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Intervention: Drug: Vorinostat

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Potential HIV infected participants who were durably suppressed (<50 copies/mL) on stable ART with a CD4 count >300/μL were recruited from the UNC ID clinic and UNC AIDS Clinical Trials Unit. Twenty seven (27) participants were screened for both study periods, 25 unique individuals enrolled between February 2011 and March 31, 2016.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were recruited into the single and multiple dose Vorinostat (VOR) Arm alone, the VOR Interval Dosing Arm alone, or both = 25. Each Arm had multiple steps. Participants without a significant in vitro or in vivo response to VOR did not advance in either Arm; 3 Arm 1 and 13 new participants, enrolled Arm 2.

Reporting Groups
  Description
Single and Multiple Dose There are 3 Steps in this Arm: Step 1 a Baseline leukapheresis was completed to obtain resting CD4+ T cells for quantitation of resting CD4+ T cell infection (RCI) and resting CD4+ T cell- associated HIV RNA (RCVL); ex-vivo exposure. Step 2 measured the in-vivo response to single dose of VOR; Step 3 measured the in vivo response after each of 2 series of exposure to multiple doses of VOR 400 mg PO. In each series, 11 doses of VOR were administered for 3 days (M-T-W) and no doses for the remaining 4 days. A leukapheresis was completed 4 hours after the 11th dose to measure in vivo response.
Interval Dosing There are 4 steps in this Arm. Step 1 Baseline leukapheresis (Visit 2) to obtain resting CD4+ T cells for quantitation of resting CD4+ T cell infection (RCI) and resting CD4+ T cell- associated HIV RNA (RCVL). Ex-vivo exposure to measure RCVL responsiveness to Vorinostat. Step 2 involved measurement of in vivo response to single dose of VOR. Step 3 involved 2 doses separated by 48 or 72 hours. In vivo responsiveness measured for optimal dose interval and step advancement. Step 4 measured significance of response to VOR 400 mg PO taken every 72 hours for 10 doses.

Participant Flow:   Overall Study
    Single and Multiple Dose   Interval Dosing
STARTED   12   13 
Step 1 [1]   8   11 [2] 
Step 2 [3]   8 [4]   4 [5] 
Step 2 [6]   4 [7]   0 
Step 3 [8]   0 [9]   6 [10] 
Step 4 [11]   0 [12]   3 [13] 
COMPLETED   0   3 
NOT COMPLETED   12   10 
No ex vivo or in vivo response                4                0 
Physician Decision                3                0 
Lack of Efficacy                5                9 
No in vivo response to interval doses                0                1 
[1] Demonstrating an ex vivo response to VOR, measured in research lab, permitted study advancement
[2] The 2 participants without an ex vivo response were terminated from the study.
[3] Demonstrated an in vivo response to a single VOR 400 mg PO in Step 2
[4] These participants demonstrated an ex vivo response in Step 1
[5] The 7 participants without an in vivo response to single dose of VOR 400 mg PO were terminated.
[6] Did not demonstrate an in vivo response to VOR 400 mg PO
[7] The 4 without ex vivo response (Step 1) took a single dose to see if in vivo response would occur
[8] Demonstrated an in vivo response to multiple doses of VOR 400 mg PO
[9] None who qualified for the 2 series of 11 doses of VOR (taken M-T-W & off for 4 days for 4 wks).
[10] 3 Arm 1 participants enrolled here; 6/7 had in vivo response to 2 VOR doses given 72 hours apart.
[11] Demonstrated an in vivo response to 10 doses taken a designated intervals
[12] Arm 1 did not have a Step 4
[13] Only 3/6 completed the study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Single, Multiple and Interval Dosing Of Vorinostat 400 mg PO The study was separated into Arms for reporting purposes required in this report. The data representing the eligibility and baseline measures were the same throughout the study and are therefore reported as a composite of the entire study. Vorinostat 400 mg PO was administered in single and multiple doses in both Arm 1 and 2. The entire cohort is described below and representative of all who were enrolled in the study over the 5 year period.

Baseline Measures
   Single, Multiple and Interval Dosing Of Vorinostat 400 mg PO 
Overall Participants Analyzed 
[Units: Participants]
 25 
Age 
[Units: Participants]
Count of Participants
 
<=18 years      0   0.0% 
Between 18 and 65 years      25 100.0% 
>=65 years      0   0.0% 
Age 
[Units: Years]
Median (Full Range)
 49 
 (23 to 65) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      0   0.0% 
Male      25 100.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
 
Hispanic   1 
Black or African American   4 
Caucasian or White   20 
Region of Enrollment 
[Units: Participants]
 
United States   25 
HIV-1 RNA Categories 
[Units: Participants]
Count of Participants
 
< 50 copies/mL   25 
>= 50 copies/mL   0 
CD4 Nadir 
[Units: cells/µL]
Median (Full Range)
 403 
 (49 to 879) 
CD4 Cell Count 
[Units: cells/µL]
Median (Full Range)
 718 
 (402 to 1302) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Exhibiting an in Vivo Resting CD4+ T Cell- Associated HIV RNA (RCVL) Increase After Receiving a Single Dose of VOR 400 mg PO   [ Time Frame: Arm1: Baseline, Visit 5 and Arm 2: Baseline and Visit 3 ]

2.  Primary:   Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Each of Two Multiple Dose Cycles (11 Doses/Cycle)   [ Time Frame: Baseline, Visit 18, Visit 29 ]

3.  Primary:   Number of Participants With a Significant in Vivo Response in Resting Cell Infection (RCI) and HIV RNA After Paired Doses   [ Time Frame: Baseline, Visit 6 ]

4.  Primary:   Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Multiple (n = 10) Interval Doses   [ Time Frame: Baseline, Visit 9 ]

5.  Secondary:   Number of Participants With Measurable Changes in Plasma HIV-1 RNA   [ Time Frame: 1 week after last VOR dose ]

6.  Secondary:   Number of Participants With Confirmed Non-hematologic Toxicity >/= Grade 3 and Related to VOR Per Division of AIDS (DAIDS) Grading Table   [ Time Frame: 24 hrs following single dose and 1 week after last of multiple dose sequence ]

7.  Secondary:   Number of Participants With Confirmed Hematologic Toxicity >/= Grade 2 and Related to VOR Per Division of AIDS (DAIDS) Grading Table   [ Time Frame: 24 hrs following single dose and 1 week after last of multiple dose sequence ]

8.  Other Pre-specified:   Number of Participants Developing Cancer Within 5 Years Following >/= 8 Vorinostat Dose Exposures   [ Time Frame: From last dose Vorinostat to 5 years afterwards ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. David Margolis
Organization: UNC Chapel Hill School of Medicine
phone: 919-966-6388
e-mail: dmargo@med.unc.edu


Publications of Results:

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01319383     History of Changes
Other Study ID Numbers: CID 0807
1U01AI095052-01 ( U.S. NIH Grant/Contract )
First Submitted: March 17, 2011
First Posted: March 21, 2011
Results First Submitted: February 9, 2017
Results First Posted: June 29, 2017
Last Update Posted: June 29, 2017