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

NCT03549312 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: REB-17-22
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1-infection; Hepatitis C, Chronic; Methadone Dependence; Opioid Dependence; Bone Diseases, Metabolic; HIV/AIDS; Co-infection; Buprenorphine Dependence; HCV Coinfection

Keywords

HIV; Hepatitis C; Methadone; HIV/HCV Co-Infection; Opioid Substitution Therapy; Buprenorphine/Naloxone

Outcome Measures

Primary Outcomes (3)

• Feasibility assessment: participants approached, screened and enrolled in the study along with completed study visits

  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.

  Up to 48 weeks on Genvoya and 12 weeks of Epclusa and 48 weeks of Biktarvy

• Assessment of incidence of screen failures

  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.

  Week 96

• Adherence

  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.

  Week 96

Secondary Outcomes (5)

• HCV clearance post Epclusa therapy

  Weeks 24 and 48

• Sustained HIV Viral Load Suppression

  Weeks 4, 12, 24, 36, 48, 52, 60, 72, 84 and 96

• Discontinuation of study medication due to adverse events

  96 weeks

• Adjustments to methadone or buprenorphine/naloxone dosing over study duration

  96 weeks

• Opioid withdrawal or overdose symptoms over study duration

  96 weeks

Study Arms (1)

Switch to Genvoya Followed By HCV Therapy Then Start Biktarvy

EXPERIMENTAL

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; Drug: Epclusa; Drug: Biktarvy

Interventions

Genvoya DRUG

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.

Also known as: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Switch to Genvoya Followed By HCV Therapy Then Start Biktarvy

Epclusa DRUG

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.

Also known as: Sofosbuvir and Velpatasvir

Switch to Genvoya Followed By HCV Therapy Then Start Biktarvy

Biktarvy DRUG

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.

Also known as: Bictegravir, Emtricitabine and Tenofovir Alafenamide

Switch to Genvoya Followed By HCV Therapy Then Start Biktarvy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and Females, 18 years or older
• HIV infected (ELISA with western blot confirmation)
• HCV RNA positive for minimum of 6 months / Genotype 1-6
• 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.
• HIV RNA ≤ 50 c/mL at screening and ≤ 200 c/mL for at least 3 months prior to screening.
• CD4 ≥ 200 cells/uL at screening.
• Stage 0 to 4 fibrosis.
• On methadone or buprenorphine/naloxone as OST for at least 3 months prior to screening and deemed stable on OST by the investigator.
• Treatment naïve to all anti-HCV therapy, or treatment experienced but with no previous exposure to NS5A inhibitors.
• Ability to remain adherent to medications and study protocol as per investigator opinion
• Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening.
• Female subjects are willing to use acceptable methods of birth control as defined in the protocol.

You may not qualify if:

• 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.
• 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.
• Co-infection with hepatitis B.
• Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC.
• 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).
• 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:
• Patients who are hypersensitive to the active substance (methadone hydrochloride) or other opioid analgesics or to any ingredient in the formulation.
• Patients with a known or suspected mechanical gastrointestinal obstruction.
• Patients with a suspected surgical abdomen.
• Patients with acute asthma or other obstructive airway, and status asthmaticus.
• Patients with acute respiratory depression, elevated carbon dioxide levels in the blood, and corpulmonale.
• Patients with acute alcoholism, delirium tremors, and convulsive disorders.
• Patients with severe central nervous system depression, increased cerebrospinal or intracranial pressure, and head injury.
• Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy).
• 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.

Sponsors & Collaborators

• Saskatchewan Health Authority - Regina Area: lead
• Gilead Sciences: collaborator

Study Sites (1)

Saskatchewan Health Authority

Regina, Saskatchewan, S4P 0W5, Canada

RECRUITING

MeSH Terms

Conditions

Hepatitis C, Chronic; Opioid-Related Disorders; Bone Diseases, Metabolic; Acquired Immunodeficiency Syndrome; Coinfection; Hepatitis C

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; elvitegravir; sofosbuvir-velpatasvir drug combination; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Alexander Wong, MD

  Saskatchewan Health Authority - Regina Area

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Wong, MD

CONTACT

306-766-3915; alexander.wong@usask.ca

Dennaye Fuchs, RN

CONTACT

306-766-4521; dennaye.fuchs@saskhealthauthority.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Infectious Diseases

Study Record Dates

• First Submitted: April 22, 2018
• First Posted: June 8, 2018
• Study Start: February 1, 2018
• Primary Completion: July 21, 2020
• Study Completion: June 22, 2021
• Last Updated: December 24, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)