TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy

Hepatitis C Clinical Trial

— ATTAIN  

Official title:

Phase III in Partial and Null Responders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01485991
• Other study ID #: CR100677
• Secondary ID: TMC435HPC3001
• Status: Completed
• Phase: Phase 3
• First received: November 25, 2011
• Last updated: April 9, 2015
• Start date: February 2012
• Est. completion date: April 2014

Study information

• Verified date: April 2015
• Source: Janssen R&D Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGreat Britain: Medicines and Healthcare Products Regulatory AgencyHungary: National Institute for Quality and Organizational Development in Healthcare and MedicinesCzech Republic: State Institute for Drug ControlGreat Britain: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the efficacy of TMC435 in combination with peginterferon (PegIFN) + ribavirin (RBV) by means of establishing its non- inferiority compared to an approved regimen of telaprevir + PegIFN + RBV in patients who have previously failed PegIFN.

Description:

This study is a randomized (study drug assigned by chance like flipping a coin), double-blind (neither physician nor patient knows the name of the assigned drug), double-dummy (patients receive both active and inactive pills also called placebo), 2-arm, multicenter Phase III clinical study in adult treatment experienced Chronic Hepatitis C (CHC) genotype-1 infected patients who failed to respond during at least 1 previous course of PegINFα-2a/ RBV therapy. The purpose of the trial is to study the efficacy of TMC435 in combination with PegINFα-2a and RBV for 48 weeks of treatment compared to the approved regimen of telaprevir in combination with PegINFα-2a and RBV for 48 weeks of treatment. The study will consist of a screening period (maximum 6 weeks), treatment period (48 weeks) and post-treatment period (until 72 weeks after the start of treatment). For the first 12 weeks one group of patients will take TMC435 and TVR placebo, plus PegINFα-2a and RBV. The other group will take TMC435 placebo and TVR, plus PegINFα-2a and RBV. After 12 weeks, patients in both arms will only take PegINFα-2a and RBV up to week 48. After patients stop taking study medication, they will continue to go to the doctor's office for study visits until a total of 72 weeks after they start study treatment. Patients will be monitored for safety throughout the study. Study assessments at each study visit may include, but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 771
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patient must have had a liver biopsy before screening (or between the screening and baseline visit), unless patient cannot undergo such a procedure or has evidence of portal hypertension not associated with cirrhosis. For patients who had a liver biopsy performed more than 2 years prior to screening or without a biopsy (because of a contraindication or portal hypertension), a non-invasive staging assessment needs to be available. Non-invasive staging assessments include FibroScan, MR-Elastography, or FibroTest/FibroSure and must not be older than 6 months prior to screening

• Chronicity of hepatitis C virus (HCV) infection, as confirmed by one or both of the following: presence of anti-HCV antibody and/or HCV ribonucleic acid (RNA) at least 6 months prior to the screening visit and/or presence of fibrosis on biopsy

• Genotype 1 HCV infection with plasma HCV RNA of >10,000 IU/mL (both confirmed at screening)

• Patient must have had at least 1 documented previous course of treatment with PegINFa-2a or PegINFa-2b in combination with ribavirin (RBV) (at least 12 weeks for null responder and 20 weeks for partial responder)

Exclusion Criteria:

• Hepatic decompensation (impaired functioning of the liver), as indicated by significant laboratory abnormalities or other active diseases

• Infection with Human Immunodeficiency Virus (HIV) or non genotype 1 hepatitis C

• Liver disease not related to hepatitis C infection

• Previous chronic hepatitis C treatment, other than PegIFN and RBV

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• TMC435
TMC435 Type=exact number, unit=mg, number=150, form=capsule, route=oral use. TVR placebo Form=tablet, route=oral use. TMC435 capsule is taken once daily in addition to 2 TVR placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.
• TVR
TVR Type=exact number, unit=mg, number=375, form=tablet, route=oral use. TMC435 placebo Form=capsule, route=oral use. 2 TVR tablets are taken 3 times a day together with 150 mg TMC435 placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen R&D Ireland

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)	Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable.	12 Weeks After the Planned End of Treatment (EOT: Week 48)	No
Secondary	Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)	Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than <25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (24 weeks after the planned EOT).	24 Weeks After the Planned EOT (Week 48)	No
Secondary	Percentage of Participants With Viral Relapse	Participants are considered to have a viral relapse if both conditions as specified are met: 1) <25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (>=) 25 IU/mL during follow-up.	End of Treatment (Week 48) up to Follow-up Period (until Week 72)	No