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Switch to Maraviroc + Integrase Inhibitor

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Maryland
Sponsor:
Information provided by (Responsible Party):
David Riedel, University of Maryland
ClinicalTrials.gov Identifier:
NCT01896921
First received: June 27, 2013
Last updated: December 23, 2014
Last verified: July 2013
  Purpose

This clinical study proposes to evaluate the combination of maraviroc with an integrase strand transfer inhibitor (either raltegravir or dolutegravir) in antiretroviral-experienced patients to document the efficacy, safety, and tolerability of this combination in order to provide clinicians with a treatment regimen that minimizes the risk of metabolic complications by avoidance of NRTI/NNRTIs and PIs. The development of an alternative ART regimen which lessens the risk of metabolic complications could improve long-term adherence and reduce the risk of certain co-morbidities associated with long-term ART use. If this new combination is found to be as efficacious as the standard regimen with enhanced tolerability and improved metabolic effects, there is great potential for altering the current practice of HIV medicine.


Condition Intervention Phase
HIV
Drug: Switch to Maraviroc + Raltegravir or Dolutegravir
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Switch to Maraviroc and Integrase Strand Transfer Inhibitor Combination Therapy (a Triple Class-Sparing Regimen) for the Treatment of HIV-1-Infected Patients on Suppressive Antiretroviral Regimens

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Proportion of patients virologically suppressed (HIV RNA <50 copies/ml) at 48weeks. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean percent change in total cholesterol, LDL, and HDL [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with adverse events [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: Yes ]
  • proportion of patients who are virologically suppressed (HIV RNA < 50 copies/ml) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • telomerase activity and telomere length. [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Maraviroc + Raltegravir or Dolutegravir
Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks
Drug: Switch to Maraviroc + Raltegravir or Dolutegravir
Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks

Detailed Description:

Description of the study design:

The study will enroll 30 HIV-infected patients on a stable ART regimen with a suppressed HIV RNA < 50 copies/ml for at least one year. Patients will be switched to the experimental regimen (maraviroc 300 mg twice a day plus either raltegravir 400 mg twice a day or dolutegravir 50 mg once a-day) and followed for 96 weeks. The decision to use raltegravir or dolutegravir will be left to investigator/subject preference, as the two integrate inhibitors are largely interchangeable aside from twice daily (raltegravir) vs. daily (dolutegravir) dosing.

Primary endpoint:

  • The primary endpoint is the proportion of patients virologically suppressed (HIV RNA < 50 copies/ml) at 48 weeks.

Definitions:

  • Virologic suppression is an HIV RNA < 50 copies/ml.
  • Virologic failure is an HIV RNA ≥ 50 copies/ml confirmed on 2 separate occasions, separated by > 1 week after viral suppression.

Secondary endpoints:

  • The percent change in total cholesterol, LDL, and HDL at 48 and 96 weeks.
  • The number of adverse events.
  • The proportion of patients who are virologically suppressed (HIV RNA < 50 copies/ml) at 96 weeks.

Exploratory endpoints:

  • Telomerase activity and telomere length measured at baseline and 24, 48, and 96 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection
  • Age between 18 and 75 years
  • CD4 count nadir ≥ 250 cells/mm3
  • HIV RNA ≤ 50 copies/ml for ≥ 12 months while taking any ART regimen

    o One virologic blip ≤ 400 copies/ml permissible within the 12 months

  • CCR5 tropic virus as defined by:

    • trofile/tropism testing if available, OR
    • DNA trofile if no trofile/tropism test available and CD4 nadir 250-499 cells/mm3, OR
    • CD4 nadir ≥ 500 cells/mm3

Exclusion Criteria:

  • Age < 18 or > 75 years
  • CD4 count nadir < 250 cells/mm3
  • Dual/mixed or X4 tropic virus if tested prior to viral suppression or if performed by DNA trofile testing at any time
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limits of normal
  • Women who:

    • are currently pregnant or breastfeeding
    • are of child-bearing age and do not agree to remain abstinent or use (or have their partner use) an acceptable method of birth control throughout the study. Acceptable method of birth control is defined as intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy.
  • History of any malignancy except non-melanoma skin cancer
  • Concomitant use of drugs known to impact or be impacted in terms of pharmacokinetics or drug-drug interactions with either raltegravir or maraviroc. This includes:

    • Inducers of UGT1A1 (such as rifampin, phenytoin, phenobarbital rifabutin, St. John's wort)
    • CYP3A inhibitors (such as ketoconazole, itraconazole, clarithromycin, nefazodone, and telithromycin)
    • CYP3A inducers (such as rifampin, carbamazepine, phenobarbital and phenytoin)
  • Subject requires or is anticipated to require any of the prohibited medications noted in the protocol
  • Enrollment in an experimental protocol having received investigational agents (antiretroviral or non-antiretroviral) within 30 days of study enrollment
  • Chronic active hepatitis B infection as defined by presence of HBsAg
  • Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
  • Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
  Contacts and Locations
Choosing 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: NCT01896921

Contacts
Contact: Gregg Brogden 410-706-1660 gbrogden@ihv.umaryland.edu

Locations
United States, Maryland
University of Maryland, Institute of Human Virology Recruiting
Baltimore, Maryland, United States, 21201
Contact: Gabriel Deleon, B.S.    410-706-4322    gdeleon@ihv.umaryland.edu   
Contact: Judith Shaw    1-866-448-4448    jshaw@ihv.umaryland.edu   
Principal Investigator: David Riedel, MD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: David J Riedel, MD University of Maryland
  More Information

No publications provided

Responsible Party: David Riedel, Assistant Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT01896921     History of Changes
Other Study ID Numbers: HP-00056162
Study First Received: June 27, 2013
Last Updated: December 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
HIV

Additional relevant MeSH terms:
Dolutegravir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015