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Trial record 35 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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ClinicalTrials.gov Identifier: NCT02660905
Recruitment Status : Unknown
Verified April 2017 by Ottawa Hospital Research Institute.
Recruitment status was:  Active, not recruiting
First Posted : January 21, 2016
Last Update Posted : April 26, 2017
Sponsor:
Collaborators:
Gilead Sciences
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE October 21, 2015
First Posted Date  ICMJE January 21, 2016
Last Update Posted Date April 26, 2017
Study Start Date  ICMJE April 2016
Estimated Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2016)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02660905 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 18, 2016)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection
Official Title  ICMJE 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
Brief Summary

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

Conduct of this study is justified as it:

  1. 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.
  2. Provides additional safety data for TAF in the HIV-HCV co-infected population.
  3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  6. 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.
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:

  1. 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.
  2. Provides additional safety data for TAF in the HIV-HCV co-infected population.
  3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  6. 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Human Immunodeficiency Virus
  • Hepatitis C, Chronic
Intervention  ICMJE
  • Drug: E/C/F/TAF;
    Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy
    Other Names:
    • 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
Study Arms  ICMJE Experimental: Active Treatment
E/C/F/TAF Ledipasvir-Sofosbuvir/TAF
Interventions:
  • Drug: E/C/F/TAF;
  • Drug: Ledipasvir-Sofosbuvir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: January 18, 2016)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02660905
Other Study ID Numbers  ICMJE 20150881-01H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE
  • Gilead Sciences
  • CIHR Canadian HIV Trials Network
Investigators  ICMJE
Principal Investigator: Curtis Cooper, MD, FRCPC The Ottawa Hospital; Ottawa Hospital Research Institute
Principal Investigator: Marina Klein, MD McGill University Health Centre/Research Institute of the McGill University Health Centre
PRS Account Ottawa Hospital Research Institute
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP