SMV + SOF With/Without RBV for IFN-II Patients With CHC

Simeprevir (SMV) + Sofosbuvir (SOF) With or Without Ribavirin (RBV) for Interferon-intolerant or Ineligible (IFN-II) Patients With Chronic Hepatitis C (CHC)

Prior trials have shown that many G1 CHC patients are ineligible or intolerant to pegylated (PEG)-based regimens due to prior severe side effects, worsening of cytopenias, exacerbation of underlying psychiatric disorders, or autoimmune disorders. These patients will not be candidates for treatment with the approvals of SMV and SOF in early 2014 due to the combination with PEG-regimens. Results of the COSMOS study suggest that these patients are likely to have excellent responses to SMV+SOF with or without RBV with 12 weeks of therapy, and that 24 weeks are unnecessary. This trial is designed to rapidly enroll and be completed in order to confirm this hypothesis.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Sofosbuvir; Drug: Ribavirin; Drug: Simeprevir

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai
  • Utah
    • Murray, Utah, United States, 84123
      • Clinical Research Centers of America, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Targeted at least 20% enrollment of patients with cirrhosis
2. Adults >/= age 18 years.
3. Active infection with hepatitis C virus (HCV) genotype 1
4. Must have health insurance that covers therapy with SOF+RBV
5. Female patients of childbearing age must have a negative pregnancy test prior to initiating therapy, use at least two effective methods of contraception during treatment, and undergo monthly pregnancy tests.
6. Patients must be either IFN-ineligible due to psychiatric, autoimmune, neurological, or other causes that are confirmed appropriate by the PI; OR,
7. IFN-intolerant due to flu-like symptoms, psychiatric problems, cytopenia or other causes deemed appropriate by the PI.

Exclusion Criteria:

1. Presence of HIV co-infection
2. Presence of hepatocellular carcinoma (HCC)
3. Prior organ transplantation
4. Any history of hepatic decompensation

5. Patients taking any of the following medications:

   • Anticonvulsants- Carbamazepine, Oxcarbazepine, Phenobarbital, or Phenytoin.
   • Anti-infectives-erythromycin, clarithromycin, or telithromycin.
   • Antifungals- systemic itraconazole, ketoconazole, posaconazole, fluconazole, or voriconazole.
   • Antimycobacterials- rifampin, rifabutin or rifapentine.
   • Corticosteroids- systemic dexamethasone.
   • Propulsives- Cisapride.
   • Herbals- Milk thistle or St. John's Wart.
6. Patients that have been exposed to direct acting anti-viral agents
7. Patients with severe renal impairment (estimated Glomerular Filtration Rate (eGFR) <50 mL/min/1.73m2) or with end stage renal disease (ESRD).
8. Patients with platelet count <50 x109/L, Hemoglobin <10 g/dL, or Neutrophils <0.5 x109/L.
9. Women who are pregnant.
10. Men whose partners are pregnant or plan on becoming pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SMV+SOF; IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD)	Drug: Sofosbuvir; Drug: Simeprevir
Active Comparator: SMV+SOF+RBV; IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD) + weight-based Ribavirin 1000-1200 mg/day	Drug: Sofosbuvir; Drug: Ribavirin; Drug: Simeprevir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Viral Response	Comparison of sustained virologic response at 12 weeks post-treatment (SVR12) in 2 arms of IFN-II patients: one receiving 12 weeks of simeprevir (SMV) (150mg QD)+ sofosbuvir (SOF) (400mg QD) and the second receiving to SMV (150mg QD)+SOF (400mg QD)+weight-based ribavirin (RBV) 1000-1200 mg/day. SVR12 is defined as a patient having undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks post-treatment. Achieving SVR12 is generally indicative of hepatitis C infection being cured.	12 weeks

Collaborators and Investigators

• Sponsor: SC Liver Research Consortium, LLC
• Collaborators: Janssen, LP
• Investigators: Principal Investigator: Paul Pockros, MD, Scripps Clinic

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 8, 2014
• First Posted (Estimate): August 12, 2014

Study Record Updates

• Last Update Posted (Actual): June 19, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Sofosbuvir; Ribavirin; Simeprevir
• Other Study ID Numbers: PJPIIS-01-14