IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1

Hepatitis C, Chronic Clinical Trial

Official title:

A Phase III, Randomized, Partially Double-Blind and Placebo-Controlled Study of BI 207127 in Combination With Faldaprevir and Ribavirin in Treatment-Naive Patients With Chronic Genotype 1 HCV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732796
• Other study ID #: 1241.20
• Secondary ID: 2012-003533-41
• Status: Completed
• Phase: Phase 3
• First received: November 6, 2012
• Last updated: February 4, 2015
• Start date: December 2012
• Est. completion date: January 2015

Study information

• Verified date: February 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Medicines and Medical Devices AgencyCanada: Health CanadaFrance: Agence Nationale sécurité médicament et des produits santéGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIreland: Irish Medicines BoardItaly: Ethics CommitteeNetherlands: Central Committee Research Involving Human SubjectsPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencyRussia: Pharmacological Committee, Ministry of HealthSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to confirm efficacy of treatment for 16 and 24 weeks in chronically infected HCV GT1b treatment naïve patients, including patients with compensated cirrhosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 470
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Chronic hepatitis C infection, diagnosed by positive HCV Ab or detectable HCV RNA at screening in addition to at least one of the following:

1. positive HCV RNA or HCV antibodies at least 6 months prior to screening, or

2. liver biopsy typical of chronic hepatitis C , or

3. history of elevated ALT at least 6 months prior to screening.

• HCV infection of sub-GT1b confirmed by genotypic testing at screening

• Treatment naïve defined as:

1. no prior treatment with any interferon, pegylated interferon, and /or ribavirin and

2. no prior treatment with at least one dose of any other licensed or investigational antiviral agent for acute or chronic hepatitis C infection

• Plasma HCV RNA > or = 1,000 IU/mL at screening

• Liver biopsy within three years or fibroscan within six months prior to randomization. Patients with compensated liver cirrhosis (score Child-Pugh A) could also be included.

• Age 18 to 75 years

• Female patients with a negative urine pregnancy test (dipstick) at Visit 2 prior to randomization

1. with documented hysterectomy, or

2. who have had both ovaries removed, or

3. with documented tubal ligation, or

4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or

5. of childbearing potential with a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 (Visit 2), that agree to use two non-hormonal methods of birth control from the date of screening until months after the last dose of ribavirin. They must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin. Medically accepted methods of contraception for females in this trial are diaphragm with spermicide substance, intrauterine devices, cervical caps and condoms.

OR:

Male patients

1. who are documented to be sterile, or

2. who consistently and correctly use a condom while their female partners (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin, and

3. without pregnant female partners. It is in the responsibility of the male patient to ensure that his partner (or partners) is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and follow-up phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor).

Exclusion criteria:

• HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening.

• HCV subtype 1a, mixed 1a/1b or GT1 undefined

• Evidence of liver disease mainly due to causes other than chronic HCV infection such as autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis or Wilson's disease

• HIV-1 or HIV-2 infection

• Hepatitis B virus (HBV) infection based on presence of HBs-Ag

• Evidence of decompensated liver disease, or history of decompensated liver disease, defined as history of ascites, hepatic encephalopathy, or bleeding esophageal varices,

• International Normalized Ratio (INR) > or =1.7

• Serum albumin < 3.3 g/dL

• Serum total bilirubin >2.0 times the upper limit of normal (ULN) with direct/indirect ratio >1, unless history of Gilbert's disease

• Active or suspected malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)

• Patients with ongoing or historical photosensitivity or recurrent rash

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C, Chronic

Intervention

Drug:
• Ribavirin (RBV)
24 weeks of active RBV
• BI 201335 (Faldaprevir)
16 weeks of BI 201335 followed by 8 weeks placebo to BI 201335
• Ribavirin (RBV)
24 weeks of active RBV
• BI 207127
24 weeks of BI 207127
• BI 201335 (Faldaprevir)
24 weeks of BI 201335
• Ribavirin (RBV)
16 weeks of Ribavirin followed by 8 weeks of placebo to Ribavirin
• BI 207127
16 weeks BI 207127 followed by 8 weeks placebo to BI 207127
• Faldaprevir (BI 201335)
24 weeks of 201335
• BI 207127
24 weeks of BI 207127

Locations

Country	Name	City	State
Austria	1241.20.43003 Boehringer Ingelheim Investigational Site	Graz
Canada	1241.20.01006 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1241.20.01007 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1241.20.01002 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1241.20.01001 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1241.20.01008 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1241.20.01010 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1241.20.01003 Boehringer Ingelheim Investigational Site	Victoria	British Columbia
Canada	1241.20.01005 Boehringer Ingelheim Investigational Site	Whitby	Ontario
France	1241.20.33003 Boehringer Ingelheim Investigational Site	Clermont-Ferrand Cedex
France	1241.20.33004 Boehringer Ingelheim Investigational Site	Lyon
France	1241.20.33006 Boehringer Ingelheim Investigational Site	Marseille Cedex 08
France	1241.20.33001 Boehringer Ingelheim Investigational Site	Montpellier Cedex 5
France	1241.20.33005 Boehringer Ingelheim Investigational Site	Nice Cedex 3
France	1241.20.33007 Boehringer Ingelheim Investigational Site	Paris
France	1241.20.33002 Boehringer Ingelheim Investigational Site	Pessac Cedex
France	1241.20.33009 Boehringer Ingelheim Investigational Site	Rennes Cedex 09
France	1241.20.33008 Boehringer Ingelheim Investigational Site	Vandoeuvre Cedex
Germany	1241.20.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	1241.20.49004 Boehringer Ingelheim Investigational Site	Berlin
Germany	1241.20.49012 Boehringer Ingelheim Investigational Site	Bonn
Germany	1241.20.49001 Boehringer Ingelheim Investigational Site	Frankfurt am Main
Germany	1241.20.49014 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1241.20.49009 Boehringer Ingelheim Investigational Site	Herne
Germany	1241.20.49008 Boehringer Ingelheim Investigational Site	Kiel
Germany	1241.20.49013 Boehringer Ingelheim Investigational Site	Köln
Germany	1241.20.49011 Boehringer Ingelheim Investigational Site	Leipzig
Germany	1241.20.49006 Boehringer Ingelheim Investigational Site	Magdeburg
Germany	1241.20.49003 Boehringer Ingelheim Investigational Site	München
Germany	1241.20.49010 Boehringer Ingelheim Investigational Site	Oberhausen
Germany	1241.20.49005 Boehringer Ingelheim Investigational Site	Ulm
Germany	1241.20.49007 Boehringer Ingelheim Investigational Site	Würzburg
Hungary	1241.20.36001 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1241.20.36002 Boehringer Ingelheim Investigational Site	Kaposvar
Ireland	1241.20.35301 Boehringer Ingelheim Investigational Site	Dublin
Ireland	1241.20.35302 Boehringer Ingelheim Investigational Site	Dublin
Ireland	1241.20.35303 Boehringer Ingelheim Investigational Site	Dublin 8
Italy	1241.20.39007 Boehringer Ingelheim Investigational Site	Ancona
Italy	1241.20.39003 Boehringer Ingelheim Investigational Site	Brescia
Italy	1241.20.39002 Boehringer Ingelheim Investigational Site	Milano
Italy	1241.20.39008 Boehringer Ingelheim Investigational Site	Milano
Italy	1241.20.39006 Boehringer Ingelheim Investigational Site	Napoli
Italy	1241.20.39005 Boehringer Ingelheim Investigational Site	Pavia
Italy	1241.20.39001 Boehringer Ingelheim Investigational Site	Torino
Italy	1241.20.39004 Boehringer Ingelheim Investigational Site	Torino
Netherlands	1241.20.31001 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1241.20.31003 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1241.20.31004 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1241.20.31006 Boehringer Ingelheim Investigational Site	Den Haag
Netherlands	1241.20.31005 Boehringer Ingelheim Investigational Site	Groningen
Portugal	1241.20.35103 Boehringer Ingelheim Investigational Site	Aveiro
Portugal	1241.20.35104 Boehringer Ingelheim Investigational Site	Coimbra
Portugal	1241.20.35101 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1241.20.35102 Boehringer Ingelheim Investigational Site	Porto
Portugal	1241.20.35105 Boehringer Ingelheim Investigational Site	Vila Real
Romania	1241.20.40001 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1241.20.40002 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1241.20.40003 Boehringer Ingelheim Investigational Site	Bucharest
Russian Federation	1241.20.70002 Boehringer Ingelheim Investigational Site	Chelyabinsk
Russian Federation	1241.20.70001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1241.20.70004 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1241.20.70005 Boehringer Ingelheim Investigational Site	St. Petersburg
Spain	1241.20.34007 Boehringer Ingelheim Investigational Site	A Coruña
Spain	1241.20.34004 Boehringer Ingelheim Investigational Site	Alicante
Spain	1241.20.34002 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1241.20.34005 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1241.20.34003 Boehringer Ingelheim Investigational Site	Madrid
Spain	1241.20.34001 Boehringer Ingelheim Investigational Site	Majadahonda, Madrid
Spain	1241.20.34008 Boehringer Ingelheim Investigational Site	Santander
Spain	1241.20.34006 Boehringer Ingelheim Investigational Site	Valencia
United Kingdom	1241.20.44005 Boehringer Ingelheim Investigational Site	Bristol
United Kingdom	1241.20.44007 Boehringer Ingelheim Investigational Site	Liverpool
United Kingdom	1241.20.44001 Boehringer Ingelheim Investigational Site	London
United Kingdom	1241.20.44002 Boehringer Ingelheim Investigational Site	London
United Kingdom	1241.20.44006 Boehringer Ingelheim Investigational Site	London
United Kingdom	1241.20.44004 Boehringer Ingelheim Investigational Site	Nottingham
United Kingdom	1241.20.44003 Boehringer Ingelheim Investigational Site	Southampton
United States	1241.20.00005 Boehringer Ingelheim Investigational Site	Austin	Texas
United States	1241.20.00018 Boehringer Ingelheim Investigational Site	Baltimore	Maryland
United States	1241.20.00002 Boehringer Ingelheim Investigational Site	Chevy Chase	Maryland
United States	1241.20.00033 Boehringer Ingelheim Investigational Site	Chula Vista	California
United States	1241.20.00017 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1241.20.00010 Boehringer Ingelheim Investigational Site	Decatur	Georgia
United States	1241.20.00026 Boehringer Ingelheim Investigational Site	Dothan	Alabama
United States	1241.20.00015 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida
United States	1241.20.00014 Boehringer Ingelheim Investigational Site	Fort Pierce	Florida
United States	1241.20.00012 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1241.20.00022 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1241.20.00006 Boehringer Ingelheim Investigational Site	La Mesa	California
United States	1241.20.00009 Boehringer Ingelheim Investigational Site	Las Vegas	Nevada
United States	1241.20.00004 Boehringer Ingelheim Investigational Site	Maitland	Florida
United States	1241.20.00001 Boehringer Ingelheim Investigational Site	New Orleans	Louisiana
United States	1241.20.00016 Boehringer Ingelheim Investigational Site	New York	New York
United States	1241.20.00031 Boehringer Ingelheim Investigational Site	New York	New York
United States	1241.20.00003 Boehringer Ingelheim Investigational Site	Oceanside	California
United States	1241.20.00013 Boehringer Ingelheim Investigational Site	Portland	Oregon
United States	1241.20.00008 Boehringer Ingelheim Investigational Site	Poway	California
United States	1241.20.00020 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1241.20.00019 Boehringer Ingelheim Investigational Site	Rochester	New York
United States	1241.20.00032 Boehringer Ingelheim Investigational Site	Springfield	Massachusetts
United States	1241.20.00024 Boehringer Ingelheim Investigational Site	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Hungary,  Ireland,  Italy,  Netherlands,  Portugal,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Virologic Response at Week 12 after end of active treatment (SVR 12)		12 weeks	No
Secondary	Sustained Virologic Response at Week 4 after end of active treatment (SVR4)		4 weeks after end of active treatment	No
Secondary	Sustained Virologic Response at Week 24 after end of active treatment (SVR24)		24 weeks after end of active treatment	No