Role of Pegylated Interferon in Combination With Direct Acting Antivirals (DAAs) to Cure Hepatitis C As Soon As Possible (ASAP) - Hepatitis C [ASAP-C]
Overview
- Phase
- Phase 2
- Intervention
- Sofosbuvir
- Conditions
- Hepatitis C, Chronic
- Sponsor
- Johns Hopkins Bloomberg School of Public Health
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- SVR12
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary objective of this pilot trial is to compare the efficacy, measured as sustained virologic response (SVR) at least 12 weeks after completion of therapy, across three study regimens/delivery modalities: Arm 1 - 4 weeks of sofosbuvir (SOF) + daclatasvir (DAC) + pegylated interferon alfa-2a (PEG) delivered using directly observed therapy (DOT); Arm 2 - 12 weeks of SOF+DAC delivered using DOT; and Arm 3 - 12 weeks of SOF+DAC delivered as per standard of care (monthly dispensation with no DOT). Secondary objectives are 1)To compare the cost per SVR for each of the three study arms; 2) To compare adherence among persons across the three study arms; 3) To evaluate the safety, tolerability and acceptability of treatment in the three arms.
Detailed Description
This will be a non-blinded randomized clinical trial with 150 participants randomized at a 1:1:1 allocation ratio to one of three treatment arms. Arm 1: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach Arm 2: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach Arm 3: Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses) Pegylated-interferon alfa-2a (PEG) will be delivered subcutaneously once weekly. Sofosbuvir (SOF) and Daclatasvir (DAC) will be taken orally once daily for the entire study period. The study will take place at the YR Gaitonde Centre for AIDS Education (YRG) and Johns Hopkins University (JHU) Collaborative Integrated Care Center (YRG-JHU ICC) located within the premises of the Chattisgarh Institute of Medical Sciences (CIMS) in Bilaspur in the state of Chattisgarh, India. Participants will be recruited from the YRG-JHU ICC in Bilaspur, which currently has 514 registered HCV antibody positive clients. The Bilaspur ICC is in the Chattisgarh Institute for Medical Sciences (CIMS). The primary outcome will be sustained virologic response (SVR12). Secondary outcomes include cost per SVR12, adherence, safety and tolerability.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent
- •Age ≥ 18 years
- •Documented evidence of chronic HCV infection (HCV RNA positive)
- •Participant is a resident of Bilaspur and can provide locator information that can be verified by one of the study staff
- •If participant is co-infected with HIV, he/she must have a cluster of differentiation 4 (CD4) \> 350 cells/mm3 and be either: 1) antiretroviral therapy (ART) naïve or 2) on ART be on a tenofovir-containing regimen. If a subject's CD4 drops below 350 cells/μl (current threshold for HIV treatment in India), he/she will be able to initiate ART but we will ensure that the subject starts on a tenofovir-containing regimen, which is currently the standard for persons newly initiating ART in India.
- •Subjects must have the following laboratory parameters at screening:
- •alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)
- •aspartate aminotransferase (AST) ≤ 10 x ULN
- •Hemoglobin ≥ 10 g/dl for male and 9 g/dl for female subjects
- •International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
Exclusion Criteria
- •Pregnant or nursing female
- •Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage, model for end-stage liver disease (MELD)\<12)
- •Prior treatment for hepatitis C virus infection
- •Infection with hepatitis B virus (HBsAg positive)
- •Chronic use of systematically administered immunosuppressive agents (e.g., prednisone equivalent \>10 mg/day)
- •Use of any prohibited concomitant medications within 28 days of the Baseline/Day 1 visit.
- •Contraindications to PEG
- •Known hypersensitivity to the metabolites or formulation excipients of PEG (for Arm 1 subjects)
- •Active significant psychiatric condition(s) including severe depression, severe bipolar disorder and schizophrenia. Other psychiatric disorders are permitted if the condition is well controlled with a stable treatment regimen for ≥ 1 year from screening, or inactive for ≥ 1 year from screening.
- •Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, psoriasis of greater than mild severity)
Arms & Interventions
SOF+DAC+PEG
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach
Intervention: Sofosbuvir
SOF+DAC+PEG
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach
Intervention: Daclatasvir
SOF+DAC+PEG
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach
Intervention: Pegylated Interferon alfa-2a
SOF+DAC, DOT
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach
Intervention: Sofosbuvir
SOF+DAC, DOT
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach
Intervention: Daclatasvir
SOF+DAC, standard
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses)
Intervention: Sofosbuvir
SOF+DAC, standard
Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses)
Intervention: Daclatasvir
Outcomes
Primary Outcomes
SVR12
Time Frame: 12 weeks after treatment completion, 16 weeks for SOF+DAC+PEG and 24 weeks for SOF+DAC
Percentage of participants achieving sustained virologic response 12 weeks quantification) after treatment is completed (SVR12) as assessed by HCV RNA less than the lower limit of quantification measured 12 weeks after treatment completion
Secondary Outcomes
- Serious Adverse Events(16 weeks for SOF+DAC+PEG and 24 weeks for SOF+DAC)
- Medication Adherence(4 weeks for SOF+DAC+PEG and 12 weeks for SOF+DAC)