Safety and Effect on HIV Transcription of Vorinostat in Patients Receiving Suppressive Combination Anti-retroviral Therapy

NCT01365065 | Unknown Phase 2 DMC

• 1 other identifier: U1111-1121-9077
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to assess the safety and ability of vorinostat, a drug currently licensed for the treatment of a type of lymphoma, to 'turn on' dormant HIV infected CD4 T-cells.

Conditions

HIV Positive

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of vorinostat on HIV transcription in CD4 T-cells.

  The primary (efficacy) endpoint of this study is to evaluate the effect of vorinostat on HIV transcription from latently infected CD4+ T-cells as measured by HIV unspliced RNA in CD4+ T-cells.

  Day 1 (before drug, 2 and 8 hours after first dose), Day 2, 7, 14, 21 and 28

Secondary Outcomes (1)

• 1. To evaluate the safety and tolerability of vorinostat in patients receiving effective combination antiretroviral therapy (cART

  Screening, Day 1, 7, 14,21, and 28

Study Arms (1)

Vorinostat

EXPERIMENTAL

Vorinostat 400mg ( 4 X 100mg ) orally daily for 14 days

Drug: Vorinostat

Interventions

Vorinostat DRUG

Vorinostat 400mg (4 x 100mg) orally daily for 14 days

Vorinostat

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV -1 infected adults
• HIV-1 plasma RNA \<50 copies/ml for at least 3 years with at least 2 viral load measures per year, and most recent viral load within 3 months of screening. Episodes of a single HIV plasma RNA 50-199 copies/ml will not exclude participation if the subsequent HIV plasma RNA was \<50 copies/ml.
• Receiving combination antiretroviral therapy (at least 3 agents)
• In the last 6 months have two CD4 cell count greater than 500 cell/µl
• Documented subtype B HIV infection
• Detectable HIV RNA on stored specimen
• Able to give informed consent

You may not qualify if:

• Any significant acute medical illness in the past 8 weeks.
• Any evidence of an active AIDS-defining opportunistic infection.
• Current or recent gastrointestinal disease that may impact the absorption of study drug.
• Any gastrointestinal surgery that could impact upon the absorption of study drug.
• Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy .
• Moderate to severe hepatic impairment
• Hepatic transaminases (AST or ALT) \> 3 x upper limit of normal (ULN)
• Hepatitis B infection as indicated by the presence of Hepatitis B surface antigen or detectable DNA levels in blood.
• A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (e.g. heart failure).
• History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
• History of diabetes mellitus
• Use of an HIV protease inhibitor.
• Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to screening.
• Use of an agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening.
• Receipt of sodium valproate or other HDAC inhibitor at any time.

Sponsors & Collaborators

• Bayside Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The Alfred Hospital - Infectious Diseases Unit

Melbourne, Victoria, 3004, Australia

Location

Related Publications (2)

• Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, Smith MZ, Spelman T, McMahon J, Velayudham P, Brown G, Roney J, Watson J, Prince MH, Hoy JF, Chomont N, Fromentin R, Procopio FA, Zeidan J, Palmer S, Odevall L, Johnstone RW, Martin BP, Sinclair E, Deeks SG, Hazuda DJ, Cameron PU, Sekaly RP, Lewin SR. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014 Nov 13;10(10):e1004473. doi: 10.1371/journal.ppat.1004473. eCollection 2014 Oct.

  PMID: 25393648 RESULT

• Mota TM, Rasmussen TA, Rhodes A, Tennakoon S, Dantanarayana A, Wightman F, Hagenauer M, Roney J, Spelman T, Purcell DFJ, McMahon J, Hoy JF, Prince HM, Elliott JH, Lewin SR. No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy. AIDS. 2017 May 15;31(8):1137-1141. doi: 10.1097/QAD.0000000000001442.

  PMID: 28301423 RESULT

MeSH Terms

Conditions

HIV Seropositivity

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: June 3, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2018
• Last Updated: April 25, 2017

Record last verified: 2017-04

Locations

AU (1)