Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy (QuaDar)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by University of British Columbia
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT02199613
First received: July 22, 2014
Last updated: NA
Last verified: July 2014
History: No changes posted
  Purpose

The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as a simplification strategy for the treatment of HIV infection in HIV-infected subjects who have had previous antiretroviral treatment experience with multiple-drug regimens.

We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will offer a safe and efficacious treatment simplification strategy for HIV positive patients currently receiving multiple-drug regimens to control their HIV infection.


Condition Intervention Phase
HIV Infection
Drug: Treatment simplification
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Plasma HIV RNA [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Proportion of individuals with plasma HIV RNA <200copies/mL at 12 weeks following regimen switch


Secondary Outcome Measures:
  • plasma HIV RNA [ Time Frame: weeks 12, 24 and 48 ] [ Designated as safety issue: No ]
    Proportion of individuals with plasma HIV RNA < 50 copies/mL at weeks 12, 24 and 48 post switch

  • plasma HIV RNA [ Time Frame: week 24 and 48 ] [ Designated as safety issue: No ]
    Proportion of individuals with plasma HIV RNA < 200 copies/mL at week 24 and 48 post switch

  • CD4 cell count, CD4% and CD4/CD8 ratio [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
    Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.

  • serum creatinine and estimated glomerular filtration rate (eGFR) [ Time Frame: 12, 24, and 48 weeks ] [ Designated as safety issue: Yes ]
    Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.

  • Adverse event discontinuations [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Proportion of adverse events experienced necessitating switch to original regimen

  • fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) between baseline and 24 and 48 weeks.

  • Darunavir plasma concentration [ Time Frame: week 2 ] [ Designated as safety issue: No ]
    Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline

  • HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) [ Time Frame: weeks 24 and 48 ] [ Designated as safety issue: No ]
    Changes in HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) between baseline and weeks 24 and 48 following switch.

  • Adherence [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    Changes in antiretroviral adherence from baseline to 24 and 48 weeks. Adherence will be assessed using two measures: the ACTG treatment adherence questionnaire and the Medication adherence self-report inventory (MASRI).

  • Elvitegravir plasma concentrations [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Elvitegravir concentrations will be measured at day 14

  • Adverse events [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.


Estimated Enrollment: 10
Study Start Date: September 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment simplification
Open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food
Drug: Treatment simplification
Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.
Other Name: Darunavir 800mg plus Stribild tablet once daily

Detailed Description:

Eligible, consenting subjects will be assessed at baseline and weeks 2, 12, 24, 36, and 48. Study medications will be dispensed at all visits except week 2, and all participants will commence taking open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/emtricitabine/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food, following study procedures at baseline.

Assessments at the study visits will include:

  1. Complete physical exam including height and weight at baseline; symptom-directed physical exam and weight at other visits
  2. Adverse clinical events including serious adverse events (hospitalizations etc.) and medication changes at every visit.
  3. HIV RNA at each visit.
  4. CD4 and CD8 absolute counts and % at all visits except week 2.
  5. Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular filtration rate (eGFR), phosphorus, urinalysis, and unrine albumin to creatinine ratio (UACR) at each visit.
  6. Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apoliporotein B, high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.
  7. Pregnancy test for women of child-bearing potential (as defined above) at every visit except week 2. In addition, pregnancy tests will be performed monthly for women of child-bearing potential; between study visits these may be done at home.
  8. A plasma sample (3 mL) will be collected and stored once at baseline for all subjects, and used for measurement of darunavir trough (pre-dose) concentration in subjects receiving darunavir in their pre-study regimen.
  9. All subjects will take their study medication under observation in the clinic on Day 14, and plasma samples (3mL) for pharmacokinetic testing will be drawn immediately pre-dose and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Subjects will return the following day before taking their Day 15 dose for a 24-hour post-dose sample.
  10. Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline and weeks 12, 24, 36, and 48 for possible future study-related testing.
  11. The following questionnaires will be completed by participants prior to other study procedures at baseline and at weeks 24 and 48: MOS-HIV quality of life questionnaire; HIVTSQ; ACTG treatment adherence questionnaire; and the medication adherence self-report inventory (MASRI).
  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV positive adults > or = 19 years of age
  • receiving stable therapy including one or two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in conjunction with a once-daily protease inhibitor (PI) (atazanavir, lopinavir or darunavir) and twice daily raltegravir
  • Virologic suppression for >6 months, defined as plasma viral load (VL) consistently < 200 copies/mL with no evidence of prior virologic rebound (VL > 1000 copies/mL) on the NRTI/PI/Raltegravir regimen, AND VL < 50 copies/mL at time of study screening
  • Estimated glomerular filtration rate (eGFR) > o r= 70mL/min at screening

Exclusion Criteria:

  • Prior documented viral rebound > 1000 copies/mL on any raltegravir-containing regimen
  • Evidence of resistance mutations compromising raltegravir or elvitegravir activity on prior genotypes.
  • Evidence of clinically significant resistance to tenofovir on any previous genotype tests: K65R mutation, or 3 or more thymidine-analogue associated mutations (TAMS) compromising tenofovir activity
  • Evidence of resistance mutations significantly compromising darunavir activity on any previous genotypic tests
  • Current use of any nonnucleoside reverse transcriptase inhibitor (NNRTI)
  • Pregnancy or breast-feeding
  • Contraindications to tenofovir/FTC, elvitegravir, or cobicistat (e.g. previous significant toxicity, intolerance or drug interactions
  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: NCT02199613

Contacts
Contact: Marianne Harris, MD 604-806-8771 mharris@cfenet.ubc.ca

Locations
Canada, British Columbia
St. Paul's Hospital Immunodeficiency Clinic Not yet recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Marianne Harris, MD    604-806-8771    mharris@cfenet.ubc.ca   
Principal Investigator: Mark Hull, MD         
Sub-Investigator: Marianne Harris, MD         
Sub-Investigator: Julio SG Montaner, MD         
Sponsors and Collaborators
University of British Columbia
Gilead Sciences
Investigators
Principal Investigator: Mark Hull, MD University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT02199613     History of Changes
Other Study ID Numbers: H14-00490, H14-00490
Study First Received: July 22, 2014
Last Updated: July 22, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
HIV
antiretroviral therapy

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Darunavir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014