Role of Pegylated Interferon in Combination With DAAs to Cure Hepatitis C As Soon As Possible - Hepatitis C [ASAP-C]

NCT03480932 | Completed Phase 2 Results

• 1 other identifier: R01DA026727
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Keywords

directly observed therapy; sofosbuvir; daclatasvir; pegylated interferon; resource-limited setting

Outcome Measures

Primary Outcomes (1)

• SVR12

  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

  12 weeks after treatment completion, 16 weeks for SOF+DAC+PEG and 24 weeks for SOF+DAC

Secondary Outcomes (2)

• 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

Study Arms (3)

SOF+DAC+PEG

ACTIVE COMPARATOR

Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) for 4 weeks with a field-based DOT approach

Drug: Sofosbuvir; Drug: Daclatasvir; Drug: Pegylated Interferon alfa-2a

SOF+DAC, DOT

ACTIVE COMPARATOR

Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with a field-based DOT approach

Drug: Sofosbuvir; Drug: Daclatasvir

SOF+DAC, standard

ACTIVE COMPARATOR

Sofosbuvir (400mg/daily) + Daclatasvir (60mg/daily) for 12 weeks with standard of care dispensation (4 monthly doses)

Drug: Sofosbuvir; Drug: Daclatasvir

Interventions

Sofosbuvir DRUG

Direct acting antiviral agent used for the treatment of hepatitis C

Also known as: Sovaldi, Hepcvir, MyHep, Hepcinat, Resof, SoviHep

SOF+DAC+PEG; SOF+DAC, DOT; SOF+DAC, standard

Daclatasvir DRUG

Direct acting antiviral agent used for the treatment of hepatitis C

Also known as: Daklinza, Natdac, Daclahep, Dacihep, Hepdac, Mydekla

SOF+DAC+PEG; SOF+DAC, DOT; SOF+DAC, standard

Pegylated Interferon alfa-2a DRUG

Antiviral agent used for the treatment of hepatitis C

Also known as: Pegasys, Taspiance

SOF+DAC+PEG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Albumin ≥ 3 g/dl
• Direct bilirubin ≤ 1.5 x ULN
• Creatinine clearance ≥ 30 ml/min as calculated by the Cockcroft-Gault Equation
• Alpha fetoprotein \< 50 ng/ml
• Absolute neutrophil count (ANC) ≥ 1,500/μL

You may not qualify if:

• 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)
• History of clinical significant retinal disease
• Clinical evidence of cirrhosis

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• National Institute on Drug Abuse (NIDA): collaborator
• YR Gaitonde Centre for AIDS Research and Education: collaborator

Study Sites (1)

YR Gaitonde Centre for AIDS Education and Johns Hopkins University Collaborative Integrated Care Center (YRG-JHU ICC)

Bilāspur, Chhattisgarh, 495009, India

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Directly Observed Therapy

Interventions

Sofosbuvir; daclatasvir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis C; 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; Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Limitations and Caveats

Adherence measurements differ by arm (Arm 1 and 2 included daily observation of doses). Adherence assessment for Arm 3 based on participant completing a visit to pick up medication refill.

Results Point of Contact

• Title: Dr. Shruti Mehta
• Organization: Johns Hopkins Bloomberg School of Public Health

smehta@jhu.edu

4432873837

Study Officials

• Shruti Mehta, PhD, MPH

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 29, 2018
• Study Start: February 2, 2018
• Primary Completion: November 2, 2018
• Study Completion: November 2, 2018
• Last Updated: May 18, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)