Efficacy and Safety of BI 201335 (Faldaprevir) in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Genotype 1 Hepatitis C Infected Patients (STARTverso 2)

Hepatitis C Clinical Trial

Official title:

A Phase III, Randomized, Double Blind and Placebo Controlled Study of Once Daily BI 201335 120 mg for 24 Weeks and BI 201335 240 mg for 12 Weeks in Combination With Pegylated Interferon Alpha and Ribavirin in Treatment Naive Patients With Genotype 1 Chronic Hepatitis C Infection.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297270
• Other study ID #: 1220.47
• Secondary ID: 2010-021716-42
• Status: Completed
• Phase: Phase 3
• First received: February 15, 2011
• Last updated: August 18, 2015
• Start date: April 2011
• Est. completion date: April 2014

Study information

• Verified date: August 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaSouth Korea: Ministry of Food and Drug Safety (MFDS)Taiwan : Food and Drug AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this trial is to evaluate the efficacy and safety of two different treatment regimens with BI 201335, both in combination with PegIFN/RBV) as compared to standard of care (SOC) with PegIFN/RBV alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 658
• 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:

1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to:

1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or,

2. liver biopsy consistent with chronic HCV infection.

2. HCV genotype 1 infection confirmed by genotypic testing at screening.

3. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection.

4. HCV RNA = 1,000 IU/mL at screening

5. Documentation of a liver biopsy within 3 years or fibroscan within 6 months of the screening visit.

Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies obtained more than 3 years before enrolment need not be repeated. Biopsies can be waived for patients who would be placed at risk from the procedure. Inability to do a liver biopsy should not exclude patients from a trial.

6. Age 18 to 70 years

7. Female patients:

(c) with documented hysterectomy, (d) who have had both ovaries removed, (e) with documented tubal ligation, (f) who are post-menopausal with last menstrual period at least 12 months prior to screening, or (g) of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, 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 in addition to the consistent and correct use of a condom. Patients must agree not to 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 ethinyl estradiol-containing contraceptives, diaphragm with spermicide substance and intra-uterine device.

Male patients:

1. who are documented to be sterile, or

2. who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) 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. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase.

8. Signed informed consent form prior to trial participation

Exclusion criteria:

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

2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection.

3. HIV co-infection.

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

5. Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)

6. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months

7. A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patient¿s ability to participate in this study.

8. Usage of any investigational drugs within 28 days prior to screening, or planned usage of an investigational drug during the course of this study.

9. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 28 days prior to screening. Patients being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened.

10. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to screening and throughout the treatment phase.

11. Known hypersensitivity to any ingredient of the study drugs.

12. Alpha fetoprotein value >100 ng/mL at screening; if >20 ng/mL and =100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or MRI) within last 6 months prior to randomization (Visit 2).

13. Decompensated liver disease, or history of decompensated liver disease, as defined by the presence of: hepatic encephalopathy, ascites, or esophageal variceal bleeding and/or laboratory results of any of the following:

1. International normalized ratio (INR) of =1.7

2. Serum Albumin =3.5 g/dL

3. Serum total bilirubin =2.0 mg/dL (except when the increase is predominately due to unconjugated bilirubin and related to Gilberts syndrome).

14. Pre-existing psychiatric condition that could interfere with the subject¿s participation in and completion of the study including but not limited to prior suicidal attempt, schizophrenia, major depression syndrome, severe anxiety, severe personality disorder, a period of disability or impairment due to a psychiatric disease within the past 5 years.

Study Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• BI201335
QD BI 201335
• PegIFN/RBV

• BI201335
QD (once daily) BI 201335
• Placebo

Locations

Country	Name	City	State
Canada	1220.47.1011 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1220.47.1012 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1220.47.1013 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1220.47.1002 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1220.47.1010 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1220.47.1014 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1220.47.1004 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	1220.47.1005 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1220.47.1006 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1220.47.1015 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1220.47.1001 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1220.47.1003 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1220.47.1016 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1220.47.1007 Boehringer Ingelheim Investigational Site	Victoria	British Columbia
Canada	1220.47.1009 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
Korea, Republic of	1220.47.8204 Boehringer Ingelheim Investigational Site	Pusan
Korea, Republic of	1220.47.8205 Boehringer Ingelheim Investigational Site	Pusan
Korea, Republic of	1220.47.8203 Boehringer Ingelheim Investigational Site	Seongnam
Korea, Republic of	1220.47.8202 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1220.47.8206 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1220.47.8207 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1220.47.8201 Boehringer Ingelheim Investigational Site	Yangsan
Puerto Rico	1220.47.0034 Boehringer Ingelheim Investigational Site	San Juan
Taiwan	1220.47.8803 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1220.47.8804 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1220.47.8802 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1220.47.8801 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1220.47.8805 Boehringer Ingelheim Investigational Site	Taipei
United States	1220.47.0042 Boehringer Ingelheim Investigational Site	Annandale	Virginia
United States	1220.47.0063 Boehringer Ingelheim Investigational Site	Arlington	Texas
United States	1220.47.0022 Boehringer Ingelheim Investigational Site	Atlanta	Georgia
United States	1220.47.0029 Boehringer Ingelheim Investigational Site	Austin	Texas
United States	1220.47.0008 Boehringer Ingelheim Investigational Site	Bakersfield	California
United States	1220.47.0064 Boehringer Ingelheim Investigational Site	Baltimore	Maryland
United States	1220.47.0069 Boehringer Ingelheim Investigational Site	Baltimore	Maryland
United States	1220.47.0085 Boehringer Ingelheim Investigational Site	Baton Rouge	Louisiana
United States	1220.47.0087 Boehringer Ingelheim Investigational Site	Baton Rouge	Louisiana
United States	1220.47.0004 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1220.47.0045 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1220.47.0057 Boehringer Ingelheim Investigational Site	Bradenton	Florida
United States	1220.47.0097 Boehringer Ingelheim Investigational Site	Bronx	New York
United States	1220.47.0083 Boehringer Ingelheim Investigational Site	Brooklyn	New York
United States	1220.47.0015 Boehringer Ingelheim Investigational Site	Burlington	Vermont
United States	1220.47.0053 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina
United States	1220.47.0067 Boehringer Ingelheim Investigational Site	Chevy Chase	Maryland
United States	1220.47.0013 Boehringer Ingelheim Investigational Site	Chicago	Illinois
United States	1220.47.0055 Boehringer Ingelheim Investigational Site	Chicago	Illinois
United States	1220.47.0019 Boehringer Ingelheim Investigational Site	Chula Vista	California
United States	1220.47.0039 Boehringer Ingelheim Investigational Site	Columbus	Georgia
United States	1220.47.0010 Boehringer Ingelheim Investigational Site	Coronado	California
United States	1220.47.0017 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1220.47.0056 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1220.47.0071 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1220.47.0052 Boehringer Ingelheim Investigational Site	Decatur	Georgia
United States	1220.47.0050 Boehringer Ingelheim Investigational Site	Dothan	Alabama
United States	1220.47.0082 Boehringer Ingelheim Investigational Site	Englewood	Colorado
United States	1220.47.0043 Boehringer Ingelheim Investigational Site	Falls Church	Virginia
United States	1220.47.0078 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida
United States	1220.47.0086 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida
United States	1220.47.0060 Boehringer Ingelheim Investigational Site	Fort Worth	Texas
United States	1220.47.0081 Boehringer Ingelheim Investigational Site	Forth Worth	Texas
United States	1220.47.0027 Boehringer Ingelheim Investigational Site	Framingham	Massachusetts
United States	1220.47.0030 Boehringer Ingelheim Investigational Site	Germantown	Tennessee
United States	1220.47.0054 Boehringer Ingelheim Investigational Site	Hialeah	Florida
United States	1220.47.0009 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1220.47.0068 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1220.47.0072 Boehringer Ingelheim Investigational Site	Jackson	Tennessee
United States	1220.47.0033 Boehringer Ingelheim Investigational Site	La Jolla	California
United States	1220.47.0035 Boehringer Ingelheim Investigational Site	La Mesa	California
United States	1220.47.0046 Boehringer Ingelheim Investigational Site	Las Vegas	Nevada
United States	1220.47.0011 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1220.47.0014 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1220.47.0100 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1220.47.0079 Boehringer Ingelheim Investigational Site	Lutherville	Maryland
United States	1220.47.0088 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1220.47.0073 Boehringer Ingelheim Investigational Site	Milwaukee	Wisconsin
United States	1220.47.0032 Boehringer Ingelheim Investigational Site	Nashville	Tennessee
United States	1220.47.0041 Boehringer Ingelheim Investigational Site	Nashville	Tennessee
United States	1220.47.0066 Boehringer Ingelheim Investigational Site	Neptune	New Jersey
United States	1220.47.0049 Boehringer Ingelheim Investigational Site	New Haven	Connecticut
United States	1220.47.0101 Boehringer Ingelheim Investigational Site	New Orleans	Louisiana
United States	1220.47.0003 Boehringer Ingelheim Investigational Site	New York	New York
United States	1220.47.0006 Boehringer Ingelheim Investigational Site	New York	New York
United States	1220.47.0038 Boehringer Ingelheim Investigational Site	New York	New York
United States	1220.47.0090 Boehringer Ingelheim Investigational Site	New York	New York
United States	1220.47.0091 Boehringer Ingelheim Investigational Site	North Little Rock	Arkansas
United States	1220.47.0018 Boehringer Ingelheim Investigational Site	Oceanside	California
United States	1220.47.0044 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1220.47.0099 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1220.47.0095 Boehringer Ingelheim Investigational Site	Palm Harbor	Florida
United States	1220.47.0061 Boehringer Ingelheim Investigational Site	Phoenix	Arizona
United States	1220.47.0028 Boehringer Ingelheim Investigational Site	Portland	Oregon
United States	1220.47.0058 Boehringer Ingelheim Investigational Site	Portland	Oregon
United States	1220.47.0059 Boehringer Ingelheim Investigational Site	Poway	California
United States	1220.47.0026 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1220.47.0016 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1220.47.0024 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1220.47.0037 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1220.47.0031 Boehringer Ingelheim Investigational Site	San Francisco	California
United States	1220.47.0092 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	1220.47.0065 Boehringer Ingelheim Investigational Site	Springfield	Massachusetts
United States	1220.47.0074 Boehringer Ingelheim Investigational Site	Tampa	Florida
United States	1220.47.0023 Boehringer Ingelheim Investigational Site	Tulepo	Mississippi
United States	1220.47.0098 Boehringer Ingelheim Investigational Site	Tulsa	Oklahoma
United States	1220.47.0062 Boehringer Ingelheim Investigational Site	Vaiparaiso	Indiana
United States	1220.47.0021 Boehringer Ingelheim Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Puerto Rico,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Virologic Response 12 Weeks Post Treatment (SVR12)	Percentage of participants with sustained virologic response 12 weeks post treatment (SVR12) defined as plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level<25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.	12 weeks post treatment, up to 60 weeks	No
Secondary	Sustained Virologic Response 24 Weeks Post-treatment (SVR24)	Percentage of participants with sustained virologic response 24 weeks post-treatment (SVR24), defined as plasma HCV RNA level < 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.; Hepatitis C virus Ribonucleic acid (HCV RNA)	24 weeks post treatment, up to 72 weeks	No
Secondary	Early Treatment Success (ETS)	Percentage of participants with early treatment success (ETS), defined as a plasma HCV RNA level <25 IU/mL (detected or undetected) at week 4 and HCV RNA <25 IU/mL (undetected) at week 8.	Week 4 and week 8	No
Secondary	ALT Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12=YES	The number of participants with alanine aminotransferase (ALT) in normal range at end of treatment (EOT) when patients have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	ALT Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12= NO	The number of participants with alanine aminotransferase (ALT) in normal range at end of treatment (EOT) when patients do not have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	ALT Normalisation: ALT in Normal Range 12 Weeks Post-treatment, When SVR12=YES	The number of participants with alanine aminotransferase (ALT) in normal range 12 weeks post-treatment when patients have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	ALT Normalisation: ALT in Normal Range 12 Weeks Post-treatment, When SVR12=NO	The number of participants with alanine aminotransferase (ALT) in normal range 12 weeks post-treatment when patients do not have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	AST Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=YES	The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment when patients have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	AST Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=NO	The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment when patients do not have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	AST Normalisation: AST in Normal Range 12 Weeks Post-treatment, When SVR12=YES	The number of participants with aspartate aminotransferase (AST) in normal range 12 weeks post-treatment when patients have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	AST Normalisation: AST in Normal Range 12 Weeks Post-treatment, When SVR12=NO	The number of participants with aspartate aminotransferase (AST) in normal range 12 weeks post-treatment when patients do not have sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No

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