Clinical trial NCT01479868: 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
Official title: A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency Virus Type 1 (HIV-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus Genotype-1
Keywords: Hepatitis C virus genotype-1
Human immunodeficiency virus-type 1
HCV-1
HIV-1
TMC435
Pegylated interferon alpha-2a
PegIFNα-2a
Pegasys
Ribavirin
RBV
Copegus
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2011-11-28
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
timeFrame: 12 weeks after end of treatment (Week 24 or 48)
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
timeFrame: 24 weeks after end of treatment (Week 24 or 48)
measure: Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
timeFrame: Week 4, 12, 24, 36, and 48
measure: Percentage of Participants With On-treatment Failure
timeFrame: Week 1 to 48
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Week 1 to 48
measure: Percentage of Participants With Viral Relapse
timeFrame: Week 1 to 72
measure: Percentage of Participants With Normalized Alanine Aminotransferase Levels
timeFrame: Baseline up to Week 72
measure: Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
timeFrame: Baseline to Week 72.
measure: Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
timeFrame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
measure: Mean Change From Baseline in CD4+ Cell Count
timeFrame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
measure: Change From Baseline in CD4+ Cell Count in Percentage
timeFrame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Week 1 to Week 72
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Newark
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Lyon
country: France
city: Montpellier Cedex 5
country: France
city: Nantes
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Düsseldorf
country: Germany
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
city: Amadora
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Badalona
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Brighton
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.