A Study to Assess the Safety, Tolerability and Efficacy of TMC435 Along With Pegylated Interferon Alpha-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Patients Co-infected With Human Immunodeficiency Virus-Type 1

NCT ID: NCT01479868

Last Updated: 2014-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-08-31

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in hepatitis C virus genotype-1 infected subjects, co-infected with human immunodeficiency virus-type 1, and to evaluate the number of patients with sustained virologic response (SVR) at 12 weeks after the planned end of treatment.

Detailed Description

This is an open-label (all the people know the identity of the intervention), single arm (study will be conducted in a single group) clinical study, to evaluate the safety, tolerability and efficacy of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in adult chronic hepatitis C (CHC) genotype-1 infected patients who are co-infected with human immunodeficiency virus-type 1 (HIV-1). The study consists of 3 phases, screening phase (Week -6), treatment phase, and a follow-up phase (up to 24 weeks). In the treatment phase, patients will be classified based on their experience with previous hepatitis C virus (HCV) treatment as follows: 1) HCV treatment-naive (patients who never received medication for the treatment of HCV); 2) prior HCV relapsers (patients who received at least 24 weeks of a PegIFNα-2a and RBV-based therapy and relapsed within 1 year after the last medication intake); and 3) prior HCV non-responders (can be further classified as, null responders: patients having at least 1 prior documented course of PegIFNα-2a and RBV therapy for at least 12 consecutive weeks; or partial responders: patients having at least 20 consecutive weeks which has not been discontinued due to intolerability to PegIFNα-2a and RBV therapy). All patients will receive TMC435 once daily along with PegIFNα-2a and RBV for 12 weeks. Patients who are continuing treatment only with PegIFNα-2a and RBV will follow until 24 or 48 weeks. Pharmacokinetics will be measured after collection of blood samples. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examinations, and specific toxicities will be performed throughout the study. The total duration of treatment is approximately of 24 weeks.

Conditions

Hepatitis C Virus Genotype-1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TMC435 + pegylated interferon alpha-2a + ribavirin

Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 150 mg will be administered once daily for 12 weeks along with peginterferon alpha-2a and ribavirin.

Pegylated interferon alpha-2a

Intervention Type: DRUG

Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks.

Ribavirin

Intervention Type: DRUG

Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks.

Interventions

TMC435

TMC435 150 mg will be administered once daily for 12 weeks along with peginterferon alpha-2a and ribavirin.

Intervention Type: DRUG

Pegylated interferon alpha-2a

Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks.

Intervention Type: DRUG

Ribavirin

Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• A liver biopsy required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy
• Patients with bridging fibrosis or cirrhosis and without a liver biopsy result within 2 years prior screening must have an ultrasound taken within 2 months prior to the screening visit or during screening with no findings suspicious for hepatocellular carcinoma (HCC)
• Genotype-1 hepatitis C virus (HCV) infection
• Plasma HCV ribonucleic acid (RNA) of more than 10,000 IU per mL
• Documented human immunodeficiency virus-type 1 (HIV-1) infection at least 6 months prior to screening

Exclusion Criteria

• Patient showing evidence of hepatic decompensation (ie, history or current evidence of ascites, bleeding varices or hepatic encephalopathy, albumin serum concentration less than 3.3 gm per dL, prolonged prothrombin time [PT] expressed as international normalized ratio [INR] more than 1.5)
• Any liver disease of non-HCV etiology
• Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
• An acute HIV-1 infection; or HIV-2 infection
• Change in antiretroviral (ARV) regimen within the last 4 weeks prior screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen R&D Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Los Angeles, California, United States

Washington D.C., District of Columbia, United States

Orlando, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Newark, New Jersey, United States

Albany, New York, United States

New York, New York, United States

Dallas, Texas, United States

Houston, Texas, United States

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Lyon, , France

Montpellier, , France

Nantes, , France

Paris, , France

Berlin, , Germany

Bonn, , Germany

Cologne, , Germany

Düsseldorf, , Germany

Frankfurt, , Germany

Freiburg im Breisgau, , Germany

Hamburg, , Germany

Amadora, , Portugal

Lisbon, , Portugal

Porto, , Portugal

San Juan, , Puerto Rico

Badalona, , Spain

Elche, , Spain

Madrid, , Spain

Brighton, , United Kingdom

London, , United Kingdom

Countries

United States; Canada; France; Germany; Portugal; Puerto Rico; Spain; United Kingdom

References

Andersohn F, Claes AK, Kulp W, Mahlich J, Rockstroh JK. Simeprevir with pegylated interferon alfa 2a plus ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a meta-analysis and historical comparison. BMC Infect Dis. 2016 Jan 11;16:10. doi: 10.1186/s12879-015-1311-3.

Reference Type: DERIVED

PMID: 26753774 (View on PubMed)

Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6.

Reference Type: DERIVED

PMID: 26743093 (View on PubMed)

Dieterich D, Rockstroh JK, Orkin C, Gutierrez F, Klein MB, Reynes J, Shukla U, Jenkins A, Lenz O, Ouwerkerk-Mahadevan S, Peeters M, De La Rosa G, Tambuyzer L, Jessner W. Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study. Clin Infect Dis. 2014 Dec 1;59(11):1579-87. doi: 10.1093/cid/ciu675. Epub 2014 Sep 5.

Reference Type: DERIVED

PMID: 25192745 (View on PubMed)

Other Identifiers

TMC435-TiDP16-C212

Identifier Type: OTHER

Identifier Source: secondary_id

CR018334

Identifier Type: -

Identifier Source: org_study_id

NCT01727323

Identifier Type: -

Identifier Source: nct_alias