Clinical trial NCT01297270: 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)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-02-16
Enrollment: 658
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
timeFrame: 12 weeks post treatment, up to 60 weeks
Secondary outcomes:
measure: Sustained Virologic Response 24 Weeks Post-treatment (SVR24)
timeFrame: 24 weeks post treatment, up to 72 weeks
measure: Early Treatment Success (ETS)
timeFrame: Week 4 and week 8
measure: ALT Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: ALT Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12= NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: ALT Normalisation: ALT in Normal Range 12 Weeks Post-treatment, When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: ALT Normalisation: ALT in Normal Range 12 Weeks Post-treatment, When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: AST Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: AST Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: AST Normalisation: AST in Normal Range 12 Weeks Post-treatment, When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: AST Normalisation: AST in Normal Range 12 Weeks Post-treatment, When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1220.47.0004 Boehringer Ingelheim Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: 1220.47.0045 Boehringer Ingelheim Investigational Site
state: Alabama
city: Dothan
country: United States
facility: 1220.47.0050 Boehringer Ingelheim Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: 1220.47.0061 Boehringer Ingelheim Investigational Site
state: Arizona
city: North Little Rock
country: United States
facility: 1220.47.0091 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Bakersfield
country: United States
facility: 1220.47.0008 Boehringer Ingelheim Investigational Site
state: California
city: Chula Vista
country: United States
facility: 1220.47.0019 Boehringer Ingelheim Investigational Site
state: California
city: Coronado
country: United States
facility: 1220.47.0010 Boehringer Ingelheim Investigational Site
state: California
city: La Jolla
country: United States
facility: 1220.47.0033 Boehringer Ingelheim Investigational Site
state: California
city: La Mesa
country: United States
facility: 1220.47.0035 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1220.47.0011 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1220.47.0014 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1220.47.0100 Boehringer Ingelheim Investigational Site
state: California
city: Oceanside
country: United States
facility: 1220.47.0018 Boehringer Ingelheim Investigational Site
state: California
city: Poway
country: United States
facility: 1220.47.0059 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1220.47.0024 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1220.47.0037 Boehringer Ingelheim Investigational Site
state: California
city: San Francisco
country: United States
facility: 1220.47.0031 Boehringer Ingelheim Investigational Site
state: California
city: Englewood
country: United States
facility: 1220.47.0082 Boehringer Ingelheim Investigational Site
state: Colorado
city: New Haven
country: United States
facility: 1220.47.0049 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Bradenton
country: United States
facility: 1220.47.0057 Boehringer Ingelheim Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: 1220.47.0078 Boehringer Ingelheim Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: 1220.47.0086 Boehringer Ingelheim Investigational Site
state: Florida
city: Hialeah
country: United States
facility: 1220.47.0054 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1220.47.0088 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1220.47.0044 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1220.47.0099 Boehringer Ingelheim Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: 1220.47.0095 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1220.47.0074 Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: 1220.47.0022 Boehringer Ingelheim Investigational Site
state: Georgia
city: Columbus
country: United States
facility: 1220.47.0039 Boehringer Ingelheim Investigational Site
state: Georgia
city: Decatur
country: United States
facility: 1220.47.0052 Boehringer Ingelheim Investigational Site
state: Georgia
city: Chicago
country: United States
facility: 1220.47.0013 Boehringer Ingelheim Investigational Site
state: Illinois
city: Chicago
country: United States
facility: 1220.47.0055 Boehringer Ingelheim Investigational Site
state: Illinois
city: Vaiparaiso
country: United States
facility: 1220.47.0062 Boehringer Ingelheim Investigational Site
state: Indiana
city: Baton Rouge
country: United States
facility: 1220.47.0085 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baton Rouge
country: United States
facility: 1220.47.0087 Boehringer Ingelheim Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: 1220.47.0101 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: 1220.47.0064 Boehringer Ingelheim Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: 1220.47.0069 Boehringer Ingelheim Investigational Site
state: Maryland
city: Chevy Chase
country: United States
facility: 1220.47.0067 Boehringer Ingelheim Investigational Site
state: Maryland
city: Lutherville
country: United States
facility: 1220.47.0079 Boehringer Ingelheim Investigational Site
state: Maryland
city: Framingham
country: United States
facility: 1220.47.0027 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: 1220.47.0065 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Tulepo
country: United States
facility: 1220.47.0023 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Las Vegas
country: United States
facility: 1220.47.0046 Boehringer Ingelheim Investigational Site
state: Nevada
city: Neptune
country: United States
facility: 1220.47.0066 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: 1220.47.0097 Boehringer Ingelheim Investigational Site
state: New York
city: Brooklyn
country: United States
facility: 1220.47.0083 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1220.47.0003 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1220.47.0006 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1220.47.0038 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1220.47.0090 Boehringer Ingelheim Investigational Site
state: New York
city: Charlotte
country: United States
facility: 1220.47.0053 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: 1220.47.0021 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Tulsa
country: United States
facility: 1220.47.0098 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: 1220.47.0028 Boehringer Ingelheim Investigational Site
state: Oregon
city: Portland
country: United States
facility: 1220.47.0058 Boehringer Ingelheim Investigational Site
state: Oregon
city: Germantown
country: United States
facility: 1220.47.0030 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Jackson
country: United States
facility: 1220.47.0072 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: 1220.47.0032 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: 1220.47.0041 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: 1220.47.0063 Boehringer Ingelheim Investigational Site
state: Texas
city: Austin
country: United States
facility: 1220.47.0029 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1220.47.0017 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1220.47.0056 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1220.47.0071 Boehringer Ingelheim Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 1220.47.0060 Boehringer Ingelheim Investigational Site
state: Texas
city: Forth Worth
country: United States
facility: 1220.47.0081 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1220.47.0009 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1220.47.0068 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1220.47.0016 Boehringer Ingelheim Investigational Site
state: Texas
city: Burlington
country: United States
facility: 1220.47.0015 Boehringer Ingelheim Investigational Site
state: Vermont
city: Annandale
country: United States
facility: 1220.47.0042 Boehringer Ingelheim Investigational Site
state: Virginia
city: Falls Church
country: United States
facility: 1220.47.0043 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1220.47.0026 Boehringer Ingelheim Investigational Site
state: Virginia
city: Seattle
country: United States
facility: 1220.47.0092 Boehringer Ingelheim Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: 1220.47.0073 Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Calgary
country: Canada
facility: 1220.47.1011 Boehringer Ingelheim Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: 1220.47.1012 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1220.47.1001 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1220.47.1003 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1220.47.1016 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1220.47.1007 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1220.47.1009 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: 1220.47.1013 Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: 1220.47.1002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1220.47.1004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1220.47.1005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1220.47.1006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1220.47.1015 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1220.47.1010 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1220.47.1014 Boehringer Ingelheim Investigational Site
state: Quebec
city: Pusan
country: Korea, Republic of
facility: 1220.47.8204 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 1220.47.8205 Boehringer Ingelheim Investigational Site
city: Seongnam
country: Korea, Republic of
facility: 1220.47.8203 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.47.8202 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.47.8206 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.47.8207 Boehringer Ingelheim Investigational Site
city: Yangsan
country: Korea, Republic of
facility: 1220.47.8201 Boehringer Ingelheim Investigational Site
city: San Juan
country: Puerto Rico
facility: 1220.47.0034 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1220.47.8803 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1220.47.8804 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1220.47.8802 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1220.47.8801 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1220.47.8805 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Jensen DM, Asselah T, Dieterich D, Foster GR, Sulkowski MS, Zeuzem S, Mantry P, Yoshida EM, Moreno C, Ouzan D, Wright M, Morano LE, Buynak R, Bourliere M, Hassanein T, Nishiguchi S, Kao JH, Omata M, Paik SW, Wong DK, Tam E, Kaita K, Feinman SV, Stern JO, Scherer J, Quinson AM, Voss F, Gallivan JP, Bocher WO, Ferenci P. Faldaprevir, pegylated interferon, and ribavirin for treatment-naive HCV genotype-1: pooled analysis of two phase 3 trials. Ann Hepatol. 2016 May-Jun;15(3):333-49. doi: 10.5604/16652681.1198803.