Clinical trial NCT02660905: HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection
Official title: Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (ECF/TAF) Switch Followed by Ledipasvir-Sofosbuvir HCV Therapy in HIV-HCV Co-Infection: A CIHR Canadian HIV Trials Network-Gilead Pilot Trial Proposal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus
Hepatitis C, Chronic
Keywords: HIV-HCV co-infected
HCV
HIV
Hep C
Hepatitis C
HCV positive
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: CIHR Canadian HIV Trials Network
First posted: 2016-01-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 investigating 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) 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 \[elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide fumarate (TAF)\] 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.

Eligibility criteria: Inclusion Criteria:

* HIV infected (ELISA with western blot confirmation)
* HCV RNA positive for minimum of 6 months / Genotype 1
* Prescribed cART that may include any Department of Health and Human Services (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 3 or 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 Criteria:

* Concomitant use of drugs with contraindication drug interactions with E/C/F/TAF of SOF-LDV
* History of HIV integrase inhibitors or NRTI resistance mutations
* Platelets \<50 x10\^9/L

Primary outcomes:
measure: Proportion of approached patients who agreed to switch from their current Antiretroviral (ARV) regimen and be screened for this study
timeFrame: 52 weeks
Secondary outcomes:
measure: Proportion of subjects achieving SVR12
timeFrame: 24 weeks
measure: Proportion of subjects maintaining undetectable HIV RNA levels
timeFrame: 32 weeks
measure: Proportion of subjects initiating HCV antiviral therapy
timeFrame: 4 weeks
measure: Proportion of subjects discontinuing study medications due to adverse events
timeFrame: 32 weeks
Other outcomes:
measure: Measures of fibrosis will be assessed over the duration of the study.
timeFrame: 32 weeks
measure: Measures of serial cellular immune will be assessed over the duration of the study.
timeFrame: 32 weeks
measure: Measures of serial cytokine immune function will be assessed over the duration of the study.
timeFrame: 32 weeks
measure: Measures of metabolic function (cholesterol) will be assessed over the duration of the study
timeFrame: 32 weeks
measure: Measures of metabolic function (glucose) will be assessed over the duration of the study
timeFrame: 32 weeks
measure: Measures of metabolic function (insulin) will be assessed over the duration of the study
timeFrame: 32 weeks
measure: Measures of metabolic function (lipokine) will be assessed over the duration of the study
timeFrame: 32 weeks
measure: Patient-focused outcome - Quality of life measure will be evaluated
timeFrame: 32 weeks
measure: Patient-Focused Outcome - Physical Activity will be evaluated
timeFrame: 32 weeks
measure: Patient-Focused Outcome - Dietary status will be evaluated
timeFrame: 32 weeks
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
affiliation: The Ottawa Hospital; Ottawa Hospital Research Institute
name: Curtis Cooper, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Marina Klein, MD
role: PRINCIPAL_INVESTIGATOR
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