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Switch to Genvoya Followed by HCV Therapy With Epclusa Followed by Simplification of HIV Therapy With Biktarvy in Patients With HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy

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ClinicalTrials.gov Identifier: NCT03549312
Recruitment Status : Unknown
Verified December 2019 by Alexander Wong, MD, Saskatchewan Health Authority - Regina Area.
Recruitment status was:  Recruiting
First Posted : June 8, 2018
Last Update Posted : December 24, 2019
Gilead Sciences
Information provided by (Responsible Party):
Alexander Wong, MD, Saskatchewan Health Authority - Regina Area

Brief Summary:
The study hypothesis is to determine the feasibility of switching HIV-HCV co-infected patients receiving methadone or buprenorphine/naloxone as opioid substitution therapy with suppressed HIV RNA viral load on current antiretroviral therapy to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF, Genvoya™) followed by 12 weeks of HCV antiviral therapy with sofosbuvir/velpatasvir (SOF/VEL, Epclusa™), followed then by switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, Biktarvy™) for an additional 48 weeks.

Condition or disease Intervention/treatment Phase
HIV-1-infection Hepatitis C, Chronic Methadone Dependence Opioid Dependence Bone Diseases, Metabolic HIV/AIDS Co-infection Buprenorphine Dependence HCV Coinfection Drug: Genvoya Drug: Epclusa Drug: Biktarvy Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Switch Followed by Sofosbuvir/Velpatasvir (SOF/VEL) Antiviral HCV Therapy Followed by Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Simplification in HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy - A Pilot Feasibility Study
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : July 21, 2020
Estimated Study Completion Date : June 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Genvoya

Arm Intervention/treatment
Experimental: Switch to Genvoya Followed By HCV Therapy Then Start Biktarvy
Oral Genvoya 150/150/200/10 mg & Epclusa 400/100 mg once daily. Once completed HCV therapy, switch anti-retroviral treatment to Oral Biktarvy 50/200/25 mg.
Drug: Genvoya

Switching to Genvoya for 48 weeks in patients with HIV/HCV co-infection and stably suppressed HIV RNA, prior to starting HCV treatment, while receiving methadone or buprenorphine/naloxone as opioid substitution therapy.

Plasma HIV-1 RNA < 50 copies/mL at weeks 4, 12, 24, 36 and 48.

Other Name: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Drug: Epclusa

HCV therapy with direct-acting-antiviral therapy with Epclusa in HIV-HCV co-infected patients with suppressed HIV RNA, receiving methadone as opioid substitution therapy.

Plasma HCV RNA viral load at weeks 12, 24, 36, 48, 72 and 96.

Other Name: Sofosbuvir and Velpatasvir

Drug: Biktarvy

Switching to Biktarvy for 48 weeks in patients with HIV previously treated with Genvoya, stably supressed HIV RNA, while receiving methadone or buprenorphine/naloxone as opioid substitution therapy.

Plasma HIV-1 RNA < 50 copies/mL at weeks 52, 60, 72, 84 and 96.

Other Name: Bictegravir, Emtricitabine and Tenofovir Alafenamide

Primary Outcome Measures :
  1. Feasibility assessment: participants approached, screened and enrolled in the study along with completed study visits [ Time Frame: Up to 48 weeks on Genvoya and 12 weeks of Epclusa and 48 weeks of Biktarvy ]
    Feasibility will be measured by collecting data on the number of participants approached, screened and enrolled. In addition, feasibility will be assessed by proportion of completed study visits as outlined in the protocol.

  2. Assessment of incidence of screen failures [ Time Frame: Week 96 ]
    Screen failures will be assessed by drug-drug interactions, prior documented resistance to any component of Genvoya or Biktarvy, non-adherence to opioid substitution therapy or antiretroviral therapy.

  3. Adherence [ Time Frame: Week 96 ]
    Adherence will be assessed at key time points of the study and will be determined by patient self-report and pill count at each study visit and by reviewing the accountability logs provided to the pharmacists to keep track of dispensed and returned pills or bottles for subjects receiving their study medication from their pharmacy with their OST.

Secondary Outcome Measures :
  1. HCV clearance post Epclusa therapy [ Time Frame: Weeks 24 and 48 ]
    Proportion of participants with HCV RNA <12 copies/mL (c/mL) at Week 24 and Week 48

  2. Sustained HIV Viral Load Suppression [ Time Frame: Weeks 4, 12, 24, 36, 48, 52, 60, 72, 84 and 96 ]
    Proportion of participants who maintain suppressed HIV Viral Load (i.e. plasma HIV-1 RNA <= 50 copies/mL)

  3. Discontinuation of study medication due to adverse events [ Time Frame: 96 weeks ]
    Proportion of participants discontinuing study medications due to adverse events (overall and liver enzyme abnormalities

  4. Adjustments to methadone or buprenorphine/naloxone dosing over study duration [ Time Frame: 96 weeks ]
    Proportion of participants who required any changes in the methadone or buprenorphine/naloxone dosing deemed secondary to the use of Genvoya, Epclusa or Biktarvy

  5. Opioid withdrawal or overdose symptoms over study duration [ Time Frame: 96 weeks ]
    Proportion of participants who experience opioid withdrawal or overdose symptoms while receiving Genvoya, Epclusa or Biktarvy and methadone or buprenorphine/naloxone as OST through 96 weeks of study, as per standardized survey measures.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Male and Females, 18 years or older
  2. HIV infected (ELISA with western blot confirmation)
  3. HCV RNA positive for minimum of 6 months / Genotype 1-6
  4. Prescribed a combination ART regimen (cART) that may include any DHHS recommended or alternative regimens, which the treating physician considers is appropriate for their patient, except E/C/F/TAF or B/F/TAF at any point previously.
  5. HIV RNA ≤ 50 c/mL at screening and ≤ 200 c/mL for at least 3 months prior to screening.
  6. CD4 ≥ 200 cells/uL at screening.
  7. Stage 0 to 4 fibrosis.
  8. On methadone or buprenorphine/naloxone as OST for at least 3 months prior to screening and deemed stable on OST by the investigator.
  9. Treatment naïve to all anti-HCV therapy, or treatment experienced but with no previous exposure to NS5A inhibitors.
  10. Ability to remain adherent to medications and study protocol as per investigator opinion
  11. Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening.
  12. Female subjects are willing to use acceptable methods of birth control as defined in the protocol.

Exclusion Criteria:

  1. Have received any anti-HCV therapy previously with NS5A inhibitors. Previous treatment regimens allowed may include pegylated interferon, ribavirin, 1st generation NS3/NS4 protease inhibitors (telaprevir or boceprevir), and sofosbuvir.
  2. Have any evidence of decompensated liver disease including ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other symptoms suggestive of advanced liver disease. For cirrhotic patients with Child-Pugh Class B or C or with Pugh-Turcotte (CPT) score greater than 6 must be excluded.
  3. Co-infection with hepatitis B.
  4. Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC.
  5. Concomitant use of drugs with contraindication or drug-interactions with E/C/F/TAF on Day 1 visit or B/F/TAF on Week 48/0E visit. However, the use of any concomitant drugs with contraindication with SOF/VEL are to be stopped during the weeks of treatment (i.e. week 12-24), and only after the Principal Investigator's permission, may the use of these drugs may be continued or restarted after week 24 visit (i.e. end of SOF/VEL therapy).
  6. Have any active contraindication to the use of methadone, as listed in the product monograph for methadone and listed below, unless deemed acceptable based on the Principal Investigator's judgement:

    1. Patients who are hypersensitive to the active substance (methadone hydrochloride) or other opioid analgesics or to any ingredient in the formulation.
    2. Patients with a known or suspected mechanical gastrointestinal obstruction.
    3. Patients with a suspected surgical abdomen.
    4. Patients with acute asthma or other obstructive airway, and status asthmaticus.
    5. Patients with acute respiratory depression, elevated carbon dioxide levels in the blood, and corpulmonale.
    6. Patients with acute alcoholism, delirium tremors, and convulsive disorders.
    7. Patients with severe central nervous system depression, increased cerebrospinal or intracranial pressure, and head injury.
    8. Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy).
    9. Patients with diarrhea associated with pseudomembranous colitis caused by cephalosporins, lincomycins (including topical clindamycin) or penicillin, or to patients having diarrhea caused by poisoning, until toxic material has been eliminated from the gastrointestinal tract.
  7. Concomitant use of alcohol to a degree deemed by the investigator to be dangerous in conjunction with administration of methadone.
  8. Has documented historic resistance to any of the components of E/C/F/TAF or B/F/TAF.
  9. Has an eGFR (by MDRD equation) < 30 mL/min/1.73m2.
  10. Is pregnant, breast-feeding, or planning or suspected to get pregnant.
  11. Has any reason, in the opinion of the investigator, which would make the candidate inappropriate for participation in an investigative study involving oral medications.
  12. Involved in any other interventional HIV or HCV study during the study period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549312

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Contact: Alexander Wong, MD 306-766-3915 alexander.wong@usask.ca
Contact: Dennaye Fuchs, RN 306-766-4521 dennaye.fuchs@saskhealthauthority.ca

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Canada, Saskatchewan
Saskatchewan Health Authority Recruiting
Regina, Saskatchewan, Canada, S4P 0W5
Contact: Alexander Wong, MD    306-766-3915    alexander.wong@usask.ca   
Contact: Dennaye Fuchs, RN    306-766-4521    dennaye.fuchs@saskhealthauthority.ca   
Principal Investigator: Alexander Wong, MD         
Sub-Investigator: Stuart Skinner, MD         
Sub-Investigator: Kumudhini Karunakaran, MD         
Sponsors and Collaborators
Saskatchewan Health Authority - Regina Area
Gilead Sciences
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Principal Investigator: Alexander Wong, MD Saskatchewan Health Authority - Regina Area
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Responsible Party: Alexander Wong, MD, Assistant Professor, Division of Infectious Diseases, Saskatchewan Health Authority - Regina Area
ClinicalTrials.gov Identifier: NCT03549312    
Other Study ID Numbers: REB-17-22
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: December 24, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Alexander Wong, MD, Saskatchewan Health Authority - Regina Area:
Hepatitis C
HIV/HCV Co-Infection
Opioid Substitution Therapy
Additional relevant MeSH terms:
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Communicable Diseases
Hepatitis C
Hepatitis C, Chronic
Bone Diseases
Bone Diseases, Metabolic
Metabolic Diseases
Opioid-Related Disorders
Disease Attributes
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Blood-Borne Infections
Flaviviridae Infections
Hepatitis, Chronic
Narcotic-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Musculoskeletal Diseases
Sofosbuvir-velpatasvir drug combination