Directly Observed Therapy for HCV in Chennai, India

NCT02541409 | Completed Phase 2 Results

• 2 other identifiers: R01DA02672R01DA026727
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this pilot trial is to evaluate the feasibility of 12 weeks vs. 24 weeks of field-based directly observed therapy (DOT) for HCV therapy in a resource-limited setting. The investigators will compare treatment completion rates among 50 persons chronically infected with HCV who will be randomized to receive either 1) 12 weeks of sofosbuvir (SOF) + ribavirin (RBV) + pegylated interferon alfa-2a (PEG); or 2) 24 weeks of SOF + RBV. Treatment will be delivered daily by field workers at a location of a participants choosing. Secondary objectives are 1) To compare the efficacy of SOF+RBV with or without PEG as measured by the proportion of subjects with sustained viral response at 12 weeks after discontinuation of therapy (SVR12); 2) To evaluate the safety and tolerability of SOF+RBV with or without PEG; 3) To assess the impact of SVR12 on insulin resistance.

Conditions

Hepatitis C, Chronic

Keywords

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

Outcome Measures

Primary Outcomes (1)

• HCV Treatment Completion

  The percentage of subjects that complete their course of treatment

  12 weeks from baseline for SOF+PEG+RBV and 24 weeks from baselne for SOF+RBV

Secondary Outcomes (3)

• Sustained Virologic Response (SVR)

  24 weeks from baseline for SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV

• Serious Adverse Events

  24 weeks from baseline SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV

• Change in Insulin Resistance

  Difference from entry to 24 weeks for SOF+PEG+RBV and difference from entry to 36 weeks for SOF+RBV

Study Arms (2)

SOF+PEG+RBV

ACTIVE COMPARATOR

Sofosbuvir (400mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) + Ribavirin (800mg/daily) for 12 weeks

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

SOF+RBV

ACTIVE COMPARATOR

Sofosbuvir (400mg/daily) + Ribavirin (800mg/daily) for 24 weeks

Drug: Sofosbuvir; Drug: Ribavirin

Interventions

Sofosbuvir DRUG

Direct acting antiviral agent used for the treatment of hepatitis C

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

SOF+PEG+RBV; SOF+RBV

Pegylated Interferon alfa-2a DRUG

Antiviral agent used for the treatment of hepatitis C

Also known as: Pegasys, Taspiance

SOF+PEG+RBV

Ribavirin DRUG

Antiviral agent (guanosine analogue) used for the treatment of hepatitis C

Also known as: Rebetol, Copegus, Univirin

SOF+PEG+RBV; SOF+RBV

Eligibility Criteria

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

You may qualify if:

• Willing/able to provide consent
• Age ≥ 18
• Chronic HCV (HCV RNA positive)
• Resident of Chennai and can provide locator information
• If co-infected with HIV, must have CD4 (Cluster of Differentation 4) \> 350 cells/mm3 and either: 1) ART naïve or 2) if on ART be on a tenofovir-containing regimen. If a participant's CD4 drops below 350 cells/μl (threshold for treatment in India), will have to initiate a tenofovir-containing regimen (current standard of care).
• Participants must have the following at screening:
• Alanine Aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)
• Aspartate Aminotransferase (AST) ≤ 10 x ULN
• Hemoglobin ≥ 12 g/dl for males and 11 g/dl for females
• 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 ≥ 60 ml/min (Cockgroft-Gault Equation)
• Alpha fetoprotein \< 50 ng/ml
• Absolute neutrophil count (ANC) ≥ 1,500/μL

You may not qualify if:

• Pregnant/nursing female or male with pregnant/nursing female partner.
• Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage, MELD\<12)
• Prior hepatitis C treatment
• Infection with hepatitis B virus
• 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 RBV therapy or PEG/RBV
• Known hypersensitivity to RBV or PEG, the metabolites or formulation excipients
• Pre-existing 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.
• Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis).
• History of clinical significant retinal disease.

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 Research and Education

Chennai, Tamil Nadu, 600113, India

Location

Related Publications (1)

• Solomon SS, Sulkowski MS, Amrose P, Srikrishnan AK, McFall AM, Ramasamy B, Kumar MS, Anand S, Thomas DL, Mehta SH. Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT). J Viral Hepat. 2018 Jan;25(1):37-46. doi: 10.1111/jvh.12761. Epub 2017 Aug 14.

  PMID: 28719029 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Directly Observed Therapy

Interventions

Sofosbuvir; peginterferon alfa-2a; Ribavirin

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; Ribonucleosides; Nucleosides

Results Point of Contact

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

smehta@jhu.edu

443-287-3837

Study Officials

• Sunil S Solomon, MBBS, PhD, MPH

  Johns Hopkins School of Medicine

  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: August 31, 2015
• First Posted: September 4, 2015
• Study Start: September 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 15, 2021
• Results First Posted: April 15, 2021

Record last verified: 2021-03

Locations

IN (1)