Clinical trial NCT01485991: 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
Official title: Phase III in Partial and Null Responders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Keywords: Hepatitis C
TMC435HPC3001
TMC435
Hepatitis C Virus (HCV)
HEP C
Genotype 1
Treatment experienced
Null responders
Partial responders
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2011-12-06
Enrollment: 771
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
timeFrame: 12 Weeks After the Planned End of Treatment (EOT: Week 48)
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
timeFrame: 24 Weeks After the Planned EOT (Week 48)
measure: Percentage of Participants With Viral Relapse
timeFrame: End of Treatment (Week 48) up to Follow-up Period (until Week 72)
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Crestview Hills
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Chevy Chase
country: United States
state: Maryland
city: Jackson
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Kansas City
country: United States
state: Missouri
city: Missoula
country: United States
state: Montana
city: Newark
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Allentown
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Arlington
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Bellevue
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Buenos Aires N/A
country: Argentina
city: Buenos Aires
country: Argentina
city: Rosario, Santa Fe
country: Argentina
city: Darlinghurst
country: Australia
city: Greenslopes
country: Australia
city: Kingswood
country: Australia
city: Melbourne
country: Australia
city: Parkville - Vic
country: Australia
city: Perth
country: Australia
city: Sydney
country: Australia
city: Woolloongabba N/A
country: Australia
city: Linz
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Haine-Saint-Paul, La Louviere
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Campinas
country: Brazil
city: Ribeirão Preto
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czech Republic
city: Karlovy Vary
country: Czech Republic
city: Plzen
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Praha 4
country: Czech Republic
city: Copenhagen
country: Denmark
city: Hvidovre N/A
country: Denmark
city: Odense N/A
country: Denmark
city: Grenoble
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Nice
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Pessac
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Frankfurt N/A
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Kiel
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Stuttgart
country: Germany
city: Ulm
country: Germany
city: Würzburg
country: Germany
city: Alexandroupolis
country: Greece
city: Athens
country: Greece
city: Larissa
country: Greece
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kaposvár
country: Hungary
city: Pecs
country: Hungary
city: Szeged N/A
country: Hungary
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petah Tiqva
country: Israel
city: Ramat-Gan
country: Israel
city: Tel-Aviv
country: Israel
city: Zefat
country: Israel
city: Fredrikstad
country: Norway
city: Nordbyhagen
country: Norway
city: Stavanger
country: Norway
city: Tromsø
country: Norway
city: Bydgoszcz
country: Poland
city: Chorzow
country: Poland
city: Kielce
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Myslowice
country: Poland
city: Raciborz
country: Poland
city: Warszawa
country: Poland
city: Lisboa
country: Portugal
city: Lisbon
country: Portugal
city: Porto
country: Portugal
city: Santurce
country: Puerto Rico
city: Bucuresti
country: Romania
city: Constanta
country: Romania
city: Iasi
country: Romania
city: Timisoara
country: Romania
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Santander N/A
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Lund
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Örebro
country: Sweden
city: Lugano
country: Switzerland
city: St Gallen
country: Switzerland
city: Zurich N/A
country: Switzerland
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Limited Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.