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Clinical Trials

MainTitle

HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection (CTN289)

This study is ongoing, but not recruiting participants.
Sponsor
Ottawa Hospital Research Institute

Collaborator
Gilead Sciences
CIHR Canadian HIV Trials Network

Information provided by (Responsible Party)
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier
NCT02660905

First received: October 21, 2015
Last updated: April 25, 2017
Last Verified: April 2017
History of Changes
Purpose

Purpose

This is an prospective open label pilot study conducted over 32 weeks.

A total of 25 eligible participants who are infected with HCV and HIV will be recruited from 2 Canadian HIV Trials Network (CTN) sites (Ottawa Hospital Research Institute and McGill University Health Centre)

This study is looking into the effectiveness of a combination of Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide Single Tablet Regimen (E/C/F/TAF STR) for HIV treatment and Harvoni for HCV treatment .

This study will assess the effect that the study drug has on the metabolism of sugar, the changes in fat in the bloodstream and other metabolic changes. Metabolism is the process your body uses to get or make energy from the food you eat.

This study may provide information on the impact of liver fibrosis (scarring of liver tissues) on metabolic changes before, during and after HCV antiviral therapy.

Drug-drug interactions (DDI) DDI between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified.

A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its:

  1. favorable side effect profile
  2. once daily STR formulation
  3. known DDI profile with LPV-SOF
  4. neutral effect on liver fibrosis
  5. improved kidney and bone safety profile with the use of TAF


  6. Conduct of this study is justified as it:
  7. Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile.
  8. Provides additional safety data for TAF in the HIV-HCV co-infected population.
  9. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  10. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  11. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  12. As a pilot study, the information gathered will inform the feasibility of future
clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.

Condition Intervention Phase
Human Immunodeficiency Virus
Hepatitis C, Chronic

Drug : E/C/F/TAF;
Drug : Ledipasvir-Sofosbuvir
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (ECF/TAF) Switch Followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy in HIV-HCV Co-Infection: A CIHR Canadian HIV Trials Network-Gilead Pilot Trial Proposal

Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures

  • Proportion of approached patients who agreed to switch from their current ARV regimen and be screened for this study [ Time Frame: 52 weeks ]
  • Screen failures due to Drug-drug Interactions (DDI) [ Time Frame: 52 weeks ]
  • Screen failures due to prior documented antiretroviral (ARV) resistance to Integrase Inhibitors and/or nucleoside reverse transcriptase inhibitors (NRTIs) [ Time Frame: 52 weeks ]
  • Proportion of subjects remaining >95% adherent to HIV and HCV antiviral therapies [ Time Frame: 32 weeks ]
    Adherence will be determined by patient self report and pill count at each study visit.
Secondary Outcome Measures:
  • Proportion of subjects achieving SVR12 [ Time Frame: 24 weeks ]
  • Proportion of subjects remaining HIV RNA undetectable [ Time Frame: 32 weeks ]
  • Proportion of subjects initiating HCV antiviral therapy [ Time Frame: 4 weeks ]
  • Proportion of subjects discontinuing study medications due to adverse events [ Time Frame: 32 weeks ]
    liver enzyme abnormalities
Other Outcome Measures:
  • Measures of fibrosis will be assessed over the duration of the study. [ Time Frame: 32 weeks ]
    Serial Fibroscan assessment
  • Measures of serial cellular immune will be assessed over the duration of the study. [ Time Frame: 32 weeks ]
  • Measures of serial cytokine immune function will be assessed over the duration of the study. [ Time Frame: 32 weeks ]
  • Patient-focused outcomes including quality of life measures will be evaluated [ Time Frame: 32 weeks ]
  • Patient-focused outcomes including dietary status will be evaluated [ Time Frame: 32 weeks ]
  • Patient-focused outcomes including physical activity will be evaluated [ Time Frame: week 0, week 4, week 12 ]
  • Measures of metabolic function (cholesterol) will be assessed over the duration of the study [ Time Frame: 32 weeks ]
    Serial measurement of cholesterol
  • Measures of metabolic function (glucose) will be assessed over the duration of the study [ Time Frame: 32 weeks ]
    Serial measurement of glucose
  • Measures of metabolic function (insulin) will be assessed over the duration of the study [ Time Frame: 32 weeks ]
    Serial measurement of insulin
  • Measures of metabolic function (lipokine) will be assessed over the duration of the study [ Time Frame: 32 weeks ]
    Serial measurement of lipokine

Enrollment: 25
Study Start Date: April 2016
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Active Treatment
E/C/F/TAF Ledipasvir-Sofosbuvir/TAF
Drug: E/C/F/TAF;

Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy

Other Name:
  • Genvoya
  • emtricitabine/ rilpivirine/ tenofovir disoproxil fumarate

Drug: Ledipasvir-Sofosbuvir

Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy

Other Name: Harvoni

Detailed Description:

The availability of interferon (IFN)-free HCV Direct Acting Antiviral (DAA) antiviral therapy such as Ledipasvir-Sofosbuvir (LPV-SOF) allows for broad provision of treatment for populations living with HIV-HCV. Co-infected persons frequently have competing co-morbidities and are at risk for progressive liver disease which makes adherence and combined management of HIV and HCV challenging. Simple, safe, well tolerated regimens with few drug-drug interactions could be highly beneficial in ensuring success of HCV therapy in this population. With this is mind, the optimal management of antiretroviral therapy prior to initiating LPV-SOF treatment remains unclear.
E/C/F/TAF [elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide fumerate (TAF)] will be assessed in this study because it is formulated as a single tablet which facilitates adherence by once daily dosing and reduced pill count. It is established to be affective at achieving and maintaining HIV virologic suppression. The safety profile of this HIV regimen is excellent. The E/C/F/TAF formulation assessed in this study will contain TAF. This formulation has been evaluated in HIV-infected populations and found to be of equivalent HIV antiviral activity and to have improved impact on renal and bone metabolism [ref: David Wohl, Anton Pozniak, Melanie Thompson, Edwin DeJesus, Daniel Podzamczer, Jean-Michel Molina, Gordon Crofoot, Christian Callebaut, Hal Martin, Scott McCallister. Tenofovir Alafenamide (TAF) in a Single-Tablet Regimen in Initial HIV-1 Therapy. Conference on Retroviruses and Opportunistic Infections. 113LB. February 23-26, 2015, Seattle, Washington.]. There is minimal safety data in HIV-HCV co-infection.
Drug-drug interactions (DDI) between HIV antiretrovirals and HCV antivirals remain a key obstacle to the safe and effective delivery. The DDI between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified.
A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its:

  1. favorable side effect profile
  2. once daily STR formulation
  3. known DDI profile with LPV-SOF
  4. neutral effect on liver fibrosis
  5. improved kidney and bone safety profile with the use of TAF

Conduct of this study is justified as it:
  • Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile (Complera followed by LPV-SOF). Polypharmacy in the co-infected population remains a significant challenge to therapeutic success.
  • Provides additional safety data for TAF in the HIV-HCV co-infected population.
  • Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  • Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  • Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  • As a pilot study, the information gathered will inform the feasibility of future clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.

    Eligibility

    Eligibility

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

    Criteria

    Inclusion

    • HIV infected (ELISA with western blot confirmation)
    • HCV RNA positive for minimum of 6 months / Genotype 1
    • Prescribed cART that may include any DHHS recommended or alternative regimens, which the treating physician considers, is appropriate for their patient. (We anticipate that approximately 60% will be on HIV protease inhibitor-based regimens).
    • HIV RNA BLLQ for minimum of 3 months
    • Stage 0 - 4 fibrosis
    • No evidence of liver decompensation defined as past or current ascites, bleeding varices or hepatic encephalopathy. Prior interferon, ribavirin and/or HCV protease inhibitor exposure will be allowed with the exception of cirrhotic with a past history of null response to interferon-based therapy.
    • Ability to remain adherent to medications and study protocol as per investigator opinion
    • For female subjects, not pregnant, planning or suspected to be pregnant or breast-feeding
    • Willing to use acceptable methods of birth control, as defined in protocol
    • Active substance use and/or mental health issues will not be exclusionary assuming other criteria are met. This inclusion will be restricted to those stably housed and engaged in harm reduction strategies. Our intent is to evaluate study participants who are representative of our clinical population and consider 'difficult to cure' compared to populations already evaluated in licensing studies

    • Exclusion:
    • Concomitant use of drugs with contraindication drug interactions with E/C/F/TAF of SOF-LDV
    • History of HIV integrase inihbitors or NRTI resistance mutations
    • Platelets <50 x109/L

    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: NCT02660905

    Locations

    Canada
    The Ottawa Hospital, General Campus
    Ottawa, Ontario, Canada
    The Research Institute of the McGill University Health Centre
    Montreal, Quebec, Canada, H4A 3J1

    Sponsors and Collaborators

    Ottawa Hospital Research Institute
    Gilead Sciences
    CIHR Canadian HIV Trials Network

    Investigators

    Principal Investigator: Curtis Cooper, MD, FRCPC The Ottawa Hospital; Ottawa Hospital Research Institute
    Principal Investigator: Marina Klein, MD McGill University Health Center
    More Information

    More Information


    Responsible Party: Ottawa Hospital Research Institute  
    ClinicalTrials.gov Identifier: NCT02660905   History of Changes  
    Other Study ID Numbers: 20150881-01H  
    Study First Received: October 21, 2015  
    Last Updated: April 25, 2017  
    Individual Participant Data    
    Plan to Share IPD: Undecided  

    Keywords provided by Ottawa Hospital Research Institute:

    HIV-HCV co-infected
    HCV
    HIV
    Hep C
    Hepatitis C
    HCV positive

    Additional relevant MeSH terms:
    Hepatitis
    Hepatitis C
    Immunologic Deficiency Syndromes
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Hepatitis C, Chronic
    Coinfection
    Tenofovir
    Antiviral Agents
    Emtricitabine
    Sofosbuvir
    Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
    Ledipasvir
    Cobicistat
    Ledipasvir, sofosbuvir drug combination

    ClinicalTrials.gov processed this data on October 20, 2017
    This information is provided by ClinicalTrials.gov.