Clinical trial NCT01732796: IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-11-26
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: SVR12 Rates With Historical Control
timeFrame: 12 Week (post-treatment)
measure: Comparisons of SVR12 Rates Across Treatment Arms
timeFrame: 12 Week (post-treatment)
Secondary outcomes:
measure: SVR4
timeFrame: 4 Week (post-treatment)
measure: SVR24
timeFrame: 24 Week (post-treatment)
Other outcomes:
Locations:
city: Dothan
country: United States
facility: 1241.20.00026 Boehringer Ingelheim Investigational Site
state: Alabama
city: Chula Vista
country: United States
facility: 1241.20.00033 Boehringer Ingelheim Investigational Site
state: California
city: La Mesa
country: United States
facility: 1241.20.00006 Boehringer Ingelheim Investigational Site
state: California
city: Oceanside
country: United States
facility: 1241.20.00003 Boehringer Ingelheim Investigational Site
state: California
city: Poway
country: United States
facility: 1241.20.00008 Boehringer Ingelheim Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: 1241.20.00015 Boehringer Ingelheim Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: 1241.20.00014 Boehringer Ingelheim Investigational Site
state: Florida
city: Maitland
country: United States
facility: 1241.20.00004 Boehringer Ingelheim Investigational Site
state: Florida
city: Decatur
country: United States
facility: 1241.20.00010 Boehringer Ingelheim Investigational Site
state: Georgia
city: New Orleans
country: United States
facility: 1241.20.00001 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: 1241.20.00018 Boehringer Ingelheim Investigational Site
state: Maryland
city: Chevy Chase
country: United States
facility: 1241.20.00002 Boehringer Ingelheim Investigational Site
state: Maryland
city: Springfield
country: United States
facility: 1241.20.00032 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Las Vegas
country: United States
facility: 1241.20.00009 Boehringer Ingelheim Investigational Site
state: Nevada
city: New York
country: United States
facility: 1241.20.00016 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1241.20.00031 Boehringer Ingelheim Investigational Site
state: New York
city: Rochester
country: United States
facility: 1241.20.00019 Boehringer Ingelheim Investigational Site
state: New York
city: Tulsa
country: United States
facility: 1241.20.00024 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: 1241.20.00013 Boehringer Ingelheim Investigational Site
state: Oregon
city: Austin
country: United States
facility: 1241.20.00005 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1241.20.00017 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1241.20.00012 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1241.20.00022 Boehringer Ingelheim Investigational Site
state: Texas
city: Richmond
country: United States
facility: 1241.20.00020 Boehringer Ingelheim Investigational Site
state: Virginia
city: Graz
country: Austria
facility: 1241.20.43003 Boehringer Ingelheim Investigational Site
city: Vancouver
country: Canada
facility: 1241.20.01001 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1241.20.01008 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1241.20.01010 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1241.20.01003 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: 1241.20.01006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1241.20.01002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Whitby
country: Canada
facility: 1241.20.01005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1241.20.01007 Boehringer Ingelheim Investigational Site
state: Quebec
city: Clermont-Ferrand Cedex
country: France
facility: 1241.20.33003 Boehringer Ingelheim Investigational Site
city: Lyon
country: France
facility: 1241.20.33004 Boehringer Ingelheim Investigational Site
city: Marseille Cedex 08
country: France
facility: 1241.20.33006 Boehringer Ingelheim Investigational Site
city: Montpellier Cedex 5
country: France
facility: 1241.20.33001 Boehringer Ingelheim Investigational Site
city: Nice Cedex 3
country: France
facility: 1241.20.33005 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1241.20.33007 Boehringer Ingelheim Investigational Site
city: Pessac Cedex
country: France
facility: 1241.20.33002 Boehringer Ingelheim Investigational Site
city: Rennes Cedex 09
country: France
facility: 1241.20.33009 Boehringer Ingelheim Investigational Site
city: Vandoeuvre Cedex
country: France
facility: 1241.20.33008 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1241.20.49002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1241.20.49004 Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: 1241.20.49012 Boehringer Ingelheim Investigational Site
city: Frankfurt am Main
country: Germany
facility: 1241.20.49001 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1241.20.49014 Boehringer Ingelheim Investigational Site
city: Herne
country: Germany
facility: 1241.20.49009 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 1241.20.49008 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1241.20.49013 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1241.20.49011 Boehringer Ingelheim Investigational Site
city: Magdeburg
country: Germany
facility: 1241.20.49006 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1241.20.49003 Boehringer Ingelheim Investigational Site
city: Oberhausen
country: Germany
facility: 1241.20.49010 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1241.20.49005 Boehringer Ingelheim Investigational Site
city: Würzburg
country: Germany
facility: 1241.20.49007 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1241.20.36001 Boehringer Ingelheim Investigational Site
city: Kaposvar
country: Hungary
facility: 1241.20.36002 Boehringer Ingelheim Investigational Site
city: Dublin 8
country: Ireland
facility: 1241.20.35303 Boehringer Ingelheim Investigational Site
city: Dublin
country: Ireland
facility: 1241.20.35301 Boehringer Ingelheim Investigational Site
city: Dublin
country: Ireland
facility: 1241.20.35302 Boehringer Ingelheim Investigational Site
city: Ancona
country: Italy
facility: 1241.20.39007 Boehringer Ingelheim Investigational Site
city: Brescia
country: Italy
facility: 1241.20.39003 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1241.20.39002 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1241.20.39008 Boehringer Ingelheim Investigational Site
city: Napoli
country: Italy
facility: 1241.20.39006 Boehringer Ingelheim Investigational Site
city: Pavia
country: Italy
facility: 1241.20.39005 Boehringer Ingelheim Investigational Site
city: Torino
country: Italy
facility: 1241.20.39001 Boehringer Ingelheim Investigational Site
city: Torino
country: Italy
facility: 1241.20.39004 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1241.20.31001 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1241.20.31003 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1241.20.31004 Boehringer Ingelheim Investigational Site
city: Den Haag
country: Netherlands
facility: 1241.20.31006 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 1241.20.31005 Boehringer Ingelheim Investigational Site
city: Aveiro
country: Portugal
facility: 1241.20.35103 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1241.20.35104 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1241.20.35101 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1241.20.35102 Boehringer Ingelheim Investigational Site
city: Vila Real
country: Portugal
facility: 1241.20.35105 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1241.20.40001 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1241.20.40002 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1241.20.40003 Boehringer Ingelheim Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: 1241.20.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1241.20.70001 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1241.20.70004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1241.20.70005 Boehringer Ingelheim Investigational Site
city: A Coruña
country: Spain
facility: 1241.20.34007 Boehringer Ingelheim Investigational Site
city: Alicante
country: Spain
facility: 1241.20.34004 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1241.20.34002 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1241.20.34005 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1241.20.34003 Boehringer Ingelheim Investigational Site
city: Majadahonda, Madrid
country: Spain
facility: 1241.20.34001 Boehringer Ingelheim Investigational Site
city: Santander
country: Spain
facility: 1241.20.34008 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1241.20.34006 Boehringer Ingelheim Investigational Site
city: Bristol
country: United Kingdom
facility: 1241.20.44005 Boehringer Ingelheim Investigational Site
city: Liverpool
country: United Kingdom
facility: 1241.20.44007 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1241.20.44001 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1241.20.44002 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1241.20.44006 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1241.20.44004 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1241.20.44003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Sarrazin C, Castelli F, Andreone P, Buti M, Colombo M, Pol S, Calinas F, Puoti M, Olveira A, Shiffman M, Stern JO, Kukolj G, Roehrle M, Aslanyan S, Deng Q, Vinisko R, Mensa FJ, Nelson DR. HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127) and ribavirin for treatment-naive patients with chronic hepatitis C virus genotype-1b infection. Clin Exp Gastroenterol. 2016 Nov 24;9:351-363. doi: 10.2147/CEG.S111116. eCollection 2016.