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Switch to Genvoya Followed by HCV Therapy With Epclusa in Patients With HIV/HCV Co-Infection on Methadone

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03549312
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : June 8, 2018
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 who are stably suppressed on current antiretroviral therapy to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF, Genvoya™) for 12 weeks followed immediately by 12 weeks of HCV antiviral therapy with sofosbuvir/velpatasvir (SOF/VEL, Epclusa™).

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

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
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 Sofosbuvir/Velpatasvir (SOF/VEL) Antiviral HCV Therapy in HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Switch to Genvoya Followed By HCV Therapy With Epclusa
Oral Genvoya 150/150/200/10 mg & Epclusa 400/100 mg once daily
Drug: Genvoya

Switching to Genvoya for 12 weeks in patients with HIV/HCV co-infection and stably suppressed HIV RNA, prior to starting HCV treatment, while receiving methadone as opioid substitution therapy.

Plasma HIV-1 RNA < 50 copies/mL at weeks 12 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.
Other Name: Sofosbuvir and Velpatasvir

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 ]
    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. Adherence [ Time Frame: Week 48 ]
    Adherence will be assessed at every study visit using pill counts for returned study medication bottles as well as missed doses reported on medication diaries. Altogether, this data will be compiled and analyzed at the end of the study.

  3. HIV treatment outcome [ Time Frame: Week 12 ]
    Proportion of participants with suppressed HIV Viral Load (i.e. plasma HIV-1 RNA < 50 copies/mL) prior to starting HCV therapy.

  4. Sustained HIV Viral Load Suppression [ Time Frame: Week 48 ]
    Proportion of participants who maintain suppressed HIV Viral Load (i.e. plasma HIV-1 RNA < 50 copies/mL)

  5. HCV treatment outcome [ Time Frame: Week 24 ]
    Proportion of participants who achieve suppressed virologic response.

  6. Maintenance of HCV Clearance [ Time Frame: Week 48 ]
    Proportion of participation who maintain a suppressed virologic response

  7. Other treatment Outcomes [ Time Frame: Week 48 ]
    Proportion of participants who complete all study protocol procedures.

  8. Other treatment Outcomes [ Time Frame: 48 weeks ]
    Record all adverse events experienced by participants from the beginning of the study until the end of the study.

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. HIV Incidence of Virologic Failure [ Time Frame: Week 48 ]
    Proportion of participants with confirmed virologic failure (two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL) at Week 48

  3. Immunologic Responses [ Time Frame: 48 weeks ]
    Absolute values and change from baseline in plasma HIV-1 RNA (log10 c/mL) to end of treatment

  4. Immunologic Responses [ Time Frame: 48 weeks ]
    Absolute values and change from baseline in CD4+ lymphocyte count to end of treatment

  5. Number of participants with treatment-related safety problems or adverse events assessed using renal laboratory testing [ Time Frame: Weeks 0 and 48 ]
  6. Number of participants with treatment-related adverse reaction using bone mineral densitometry tests [ Time Frame: Weeks 0 and 48 ]
  7. Adjustments to methadone dosing over study duration [ Time Frame: 48 weeks ]
    Proportion of participants who required changes in the methadone dosing and deemed a secondary consequence of either Genvoya or Epculsa treatment

  8. Opioid withdrawal or overdose symptoms over study duration [ Time Frame: 48 weeks ]
    Proportion of participants who experience opioid withdrawal or overdose symptoms while receiving either Genvoya and/or Epculsa treatments

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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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. HIV infected (ELISA with western blot confirmation)
  2. HCV RNA positive for minimum of 6 months / Genotype 1-6
  3. 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 at any point previously.
  4. HIV RNA ≤ 50 c/mL at screening and ≤ 200 c/mL for at least 3 months prior to screening.
  5. CD4 ≥ 200 cells/uL at screening.
  6. Stage 0 to 4 fibrosis.
  7. On methadone as opioid substitution therapy (OST) for at least 3 months prior to screening and deemed stable on OST by the investigator. Other forms of OST such as suboxone are not permitted.
  8. Treatment naïve to all anti-HCV therapy, or treatment experienced, except any NS5A inhibitors. Ability to remain adherent to medications and study protocol as per investigator opinion
  9. Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening.
  10. 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 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 cirrhotics, 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 or SOF/VEL.
  6. Have any active contraindication to the use of methadone, as listed in the product monograph for methadone and listed below:

    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.
  9. Has an eGFR (by MDRD equation) < 30 mL/min.
  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. Participants who are involved in any other interventional HIV or HCV studies 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 identifier (NCT number): NCT03549312

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Contact: Alexander Wong, MD 306-766-3915
Contact: Dennaye Fuchs, RN 306-766-4521

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Canada, Saskatchewan
Saskatchewan Health Authority Recruiting
Regina, Saskatchewan, Canada, S4P 0W5
Contact: Alexander Wong, MD    306-766-3915   
Contact: Dennaye Fuchs, RN    306-766-4521   
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 Identifier: NCT03549312     History of Changes
Other Study ID Numbers: REB-17-22
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: May 2018
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
Drug Abuse

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
Substance-Related Disorders
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis, Chronic
Chemically-Induced Disorders
Mental Disorders
Musculoskeletal Diseases
Parasitic Diseases
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Sofosbuvir-velpatasvir drug combination