Clinical Trials

MainTitle

Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (TMC114HIV2030)

This study has been withdrawn
Sponsor
Stanford University

Collaborator
Janssen Scientific Affairs, LLC
University of Colorado, Denver

Information provided by (Responsible Party)
Philip Grant, Stanford University

ClinicalTrials.gov Identifier
NCT02499978

First received: July 14, 2015
Last updated: October 27, 2016
Last Verified: October 2016
History of Changes
Purpose

Purpose

This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic suppression at 48 weeks of treatment.

Condition Intervention Phase
HIV/AIDS

Drug : Darunavir/Cobicistat
Drug : Dolutegravir
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (The 'deNUC' Study; TMC114HIV2030)

Further study details as provided by Philip Grant, Stanford University:

Primary Outcome Measures

  • Virologic suppression (24 weeks) [ Time Frame: 24 weeks ]
    Compare between arms the proportion of patients maintaining virologic suppression (i.e., no confirmed HIV RNA levels ≥200 copies/mL) at Week 24
Secondary Outcome Measures:
  • Virologic Suppression (48 weeks) [ Time Frame: 48 weeks ]
    Evaluate the proportion of participants who maintain virologic suppression 24 weeks post-switch (i.e. at 24 weeks in the immediate switch arm and at 48 weeks in the delayed switch arm)

Enrollment: 0
Study Start Date: May 2016
Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: DRV/COBI, DTG Immediate switch
DARUNAVIR/COBICISTAT (800mg/150MG), DOLUTEGRAVIR 50MG DAILY at randomization and follow through week 48.
Drug: Darunavir/Cobicistat

Fixed dose combination medication

Other Name: Prezcobix, DRV/COBI
Drug: Dolutegravir

single tablet medication

Other Name: Tivicay, DTG
Active Comparator: DRV/COBI, DTG Delayed Switch
DARUNAVIR/COBICISTAT (800MG150MG), DOLUTEGRAVIR 50MG DAILY at week 24 and follow through week 48.
Drug: Darunavir/Cobicistat

Fixed dose combination medication

Other Name: Prezcobix, DRV/COBI
Drug: Dolutegravir

single tablet medication

Other Name: Tivicay, DTG

Detailed Description:

NRTIs have been a stalwart for treatment in both the pre- and post-ART eras. However, NRTIs have numerous toxicities partly due to the fact that they are analogs of naturally occurring nucleotides and interfere with the activity of numerous cellular functions. In highly treatment-experienced individuals with more than two active drugs in their salvage regimens, an NRTI-sparing regimen has been shown to be non-inferior to an NRTI-containing regimen [33]. However, studies with NRTI-sparing regimens not consisting of more than two active medications have generally been disappointing.
One limitation of earlier NRTI-sparing regimens has been a higher pill burden than more standard regimens. However, the approvals of DTG and the co-formulated DRV/COBI, both with well-established antiviral activities, may allow for a compact, effective, NRTI-sparing regimen. A switch to DTG/DRV/COBI in virologically suppressed HIV-infected individuals has the potential to avoid NRTI-associated toxicity while maintaining virologic suppression.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. A second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test or a previous detectable HIV RNA level.

2 .Age ≥ 18 years
  • HIV-1 RNA <50 copies/mL while on a stable antiretroviral regimen for at least 6 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements <50 copies/mL)
  • At screening, patient on a stable antiretroviral regimen containing at least one NRTI and a PI, NNRTI, or INSTI
  • No changes in antiretroviral regimen in the six months prior to screening (except for a switch to a coformulated tablet from the component tablets)
  • A desire to switch off current antiretroviral therapy due to: a) Renal dysfunction (microalbuminuria/proteinuria or CrCl<70 mL/min/1.73 m2) on tenofovir disoproxil fumarate (TDF) of tenofovir al; b) Osteopenia or osteoporosis on a TDF-containing regimen (i.e., lowest T-score ≥1.0 standard deviation below the young adult mean measured by dual-energy x-ray absorptiometry); c) Peripheral neuropathy or lipoatrophy at least partially attributable to ongoing NRTI use; d) Intermediate or high Framingham risk (i.e., ≥10% 10-year risk) on an abacavir-containing regimen; e) Patient preference.
  • Laboratory values within six months of screening visit
    • Hemoglobin ≥8.0 g/dL
    • Platelet count ≥40,000/mm3
    • AST, ALT, and alkaline phosphatase ≤5 × ULN
    • Total bilirubin ≤2.5 x ULN (except for those on atazanavir-containing regimens)
    • Calculated creatinine clearance (CrCl) ≥45 mL/min as estimated by the Cockcroft-Gault equation:

    • For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)*
      *For women, multiply the result by 0.85 = CrCl (mL/min)
      1. For women of reproductive potential, negative serum or urine pregnancy test at screening and a negative urine pregnancy test at the entry visit prior to randomization and also agreeable to using a contraceptive of choice during the study period.

      "Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation)

    Exclusion Criteria:
    • Current CD4+ T-cell count <200 cells/µL
    • Current antiretroviral regimen consisting of three of more antiretroviral classes
    • History of genotypic resistance, phenotypic resistance or intolerance to either DRV or DTG.

    • Prohibited protease mutations: V11I, V32I, L33F, I47V/A/L, I50V, I54T/S/L/M, T74P, L76V, V82F, I84V, or L89V
      Prohibited INSTI mutations: E92Q, E92K/A, G140S/A/C, Q148H/R/K or Q148 substitution plus any of the following: L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.
    • History of virologic failure while on an INSTI prior to study enrollment
    • Severe hepatic impairment (Child Pugh Class C)
    • Hepatitis B Surface Antigen Positive
    • Breastfeeding, pregnancy, or plans to become pregnant during the study
    • Known allergy/sensitivity to any study drug or their formulations.
    • Receipt or planned receipt of prohibited concomitant medications (See section 5.2.1)
    • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
    • Serious medical illness that, in the opinion of the site investigator, precludes safe participation in the study.

    contacts and locations

    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: NCT02499978

    Locations

    United States, California
    Stanford Univerity
    Stanford, California, United States, 94305
    United States, Colorado
    University of Colorado
    Aurora, Colorado, United States, 80045

    Sponsors and Collaborators

    Stanford University
    Janssen Scientific Affairs, LLC
    University of Colorado, Denver

    Investigators

    Study Director: Philip Grant, MD Stanford University
    Principal Investigator: Sean Collins, MD Stanford University
    More Information

    More Information


    Responsible Party: Philip Grant, Assistant Professor of Medicine, Stanford University  
    ClinicalTrials.gov Identifier: NCT02499978   History of Changes  
    Other Study ID Numbers: deNUC  
    Study First Received: July 14, 2015  
    Last Updated: October 27, 2016  

    Additional relevant MeSH terms:
    Darunavir
    Dolutegravir
    Cobicistat

    ClinicalTrials.gov processed this data on June 02, 2020
    This information is provided by ClinicalTrials.gov.