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

NCT ID: NCT01485991

Last Updated: 2016-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 771 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-04-30

Brief 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.

Detailed 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.

Conditions

Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TMC435/PR

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

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/PR

Group Type: ACTIVE_COMPARATOR

TVR

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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 PegINFα-2a or PegINFα-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

• 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

Tibotec Pharmaceuticals Limited Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceutical Limited

Locations

Bakersfield, California, United States

San Diego, California, United States

Aurora, Colorado, United States

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

Jacksonville, Florida, United States

Orlando, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Honolulu, Hawaii, United States

Chicago, Illinois, United States

Crestview Hills, Kentucky, United States

New Orleans, Louisiana, United States

Chevy Chase, Maryland, United States

Jackson, Mississippi, United States

Tupelo, Mississippi, United States

Kansas City, Missouri, United States

Missoula, Montana, United States

Newark, New Jersey, United States

New York, New York, United States

Rochester, New York, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Allentown, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Arlington, Texas, United States

Houston, Texas, United States

Odessa, Texas, United States

San Antonio, Texas, United States

Falls Church, Virginia, United States

Bellevue, Washington, United States

Seattle, Washington, United States

Buenos Aires, , Argentina

Rosario, Santa Fe, , Argentina

Darlinghurst, , Australia

Greenslopes, , Australia

Kingswood, , Australia

Melbourne, , Australia

Parkville - Vic, , Australia

Perth, , Australia

Sydney, , Australia

Woolloongabba, , Australia

Linz, , Austria

Vienna, , Austria

Brussels, , Belgium

Haine-Saint-Paul, La Louviere, , Belgium

Leuven, , Belgium

Liège, , Belgium

Campinas, , Brazil

Ribeirão Preto, , Brazil

Salvador, , Brazil

São Paulo, , Brazil

Sofia, , Bulgaria

Varna, , Bulgaria

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Brno, , Czechia

Karlovy Vary, , Czechia

Pilsen, , Czechia

Prague, , Czechia

Copenhagen, , Denmark

Hvidovre, , Denmark

Odense, , Denmark

Grenoble, , France

Lyon, , France

Marseille, , France

Nice, , France

Paris, , France

Pessac, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Frankfurt, , Germany

Freiburg im Breisgau, , Germany

Hamburg, , Germany

Hanover, , Germany

Heidelberg, , Germany

Kiel, , Germany

Mainz, , Germany

München, , Germany

Stuttgart, , Germany

Ulm, , Germany

Würzburg, , Germany

Alexandroupoli, , Greece

Athens, , Greece

Larissa, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Kaposvár, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Safed, , Israel

Tel Aviv, , Israel

Fredrikstad, , Norway

Nordbyhagen, , Norway

Stavanger, , Norway

Tromsø, , Norway

Bydgoszcz, , Poland

Chorzów, , Poland

Kielce, , Poland

Lodz, , Poland

Lublin, , Poland

Mysłowice, , Poland

Racibórz, , Poland

Warsaw, , Poland

Lisbon, , Portugal

Porto, , Portugal

Santurce, , Puerto Rico

Bucharest, , Romania

Constanța, , Romania

Iași, , Romania

Timișoara, , Romania

Barcelona, , Spain

Madrid, , Spain

Santander, , Spain

Seville, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Lund, , Sweden

Malmo, , Sweden

Örebro, , Sweden

Stockholm, , Sweden

Lugano, , Switzerland

Sankt Gallen, , Switzerland

Zurich, , Switzerland

Glasgow, , United Kingdom

Leeds, , United Kingdom

London, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Plymouth, , United Kingdom

Southampton, , United Kingdom

Countries

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

References

Reddy KR, Zeuzem S, Zoulim F, Weiland O, Horban A, Stanciu C, Villamil FG, Andreone P, George J, Dammers E, Fu M, Kurland D, Lenz O, Ouwerkerk-Mahadevan S, Verbinnen T, Scott J, Jessner W. Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial. Lancet Infect Dis. 2015 Jan;15(1):27-35. doi: 10.1016/S1473-3099(14)71002-3. Epub 2014 Dec 5.

Reference Type: DERIVED

PMID: 25482330 (View on PubMed)

Other Identifiers

TMC435HPC3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR100677

Identifier Type: -

Identifier Source: org_study_id