A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01330316
First received: April 5, 2011
Last updated: July 3, 2015
Last verified: July 2015
  Purpose

The objective of this trial is to collect evidence for the safety and efficacy of 24 weeks of treatment with BI 201335 240 mg in combination with 24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.


Condition Intervention Phase
Hepatitis C
Drug: BI 201335
Drug: PegIFN/RBV
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Open-label Study of Once Daily BI 201335 240 mg for 24 Weeks in Combination With Pegylated interferon-a (PegIFN) and Ribavirin (RBV) in Patients With Genotype 1 Chronic Hepatitis C Infection Who Failed a Prior PegIFN / RBV Treatment

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL [ Time Frame: 12 weeks post treatment, up to 60 weeks ] [ Designated as safety issue: No ]
    The primary endpoint was SVR12, defined as a plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.


Secondary Outcome Measures:
  • Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) [ Time Frame: 24 weeks post treatment, up to 72 weeks ] [ Designated as safety issue: No ]
    Sustained virologic response 24 weeks, defined as a plasma HCV RNA level < 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.

  • Early Treatment Success (ETS) [ Time Frame: week 4 and week 8 ] [ Designated as safety issue: No ]
    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.

  • Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) [ Time Frame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers ] [ Designated as safety issue: No ]
    This will be presented as the number of patients in/not in normal range from baseline EoT. SVR12 is sustained virological response 12 weeks post-treatment.

  • Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. [ Time Frame: 48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS ] [ Designated as safety issue: No ]
    This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.

  • Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) [ Time Frame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers. ] [ Designated as safety issue: No ]
    This will be presented as the number of patients in/not in normal range from baseline to EoT. SVR12 is sustained virological response 12 weeks post-treatment.

  • Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. [ Time Frame: Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers ] [ Designated as safety issue: No ]
    This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.

  • Occurrence of Adverse Events (Overall and by DAIDS Grade) [ Time Frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days ] [ Designated as safety issue: No ]

    This outcome measure will be presented as the percentage of subjects with any adverse event (AE).

    Percentages are calculated using total number of subjects per treatment cohort as the denominator.

    The intensity of all AEs was evaluated according to the DAIDS (Division of Acquired Immunodeficiency Syndrome) grading scale with AEs of mild, moderate, or severe intensity receiving Grades 1, 2, or 3, respectively. Adverse events judged potentially life threatening received a Grade 4 assessment.


  • Occurrence of Adverse Events Leading to Treatment Discontinuation [ Time Frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days ] [ Designated as safety issue: No ]
    This outcome measure will be presented as the percentage of subjects with adverse events leading to discontinuation of Faldaprevir and all study medication. Percentages are calculated using total number of subjects per treatment cohort as the denominator.

  • Occurrence of Serious Adverse Events (SAEs) [ Time Frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days ] [ Designated as safety issue: No ]
    This outcome measure will be presented as the percentage of subjects with any serious adverse event (SAE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.

  • Occurrence of Drug-related AEs as Assessed by the Investigator [ Time Frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days ] [ Designated as safety issue: No ]
    This outcome measure will be presented as the percentage of subjects with any drug-related AEs as assessed by the investigator. Percentages are calculated using total number of subjects per treatment cohort as the denominator.

  • Laboratory Test Abnormalities by DAIDS Grades [ Time Frame: baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study ] [ Designated as safety issue: No ]
    This Outcome measure will be presented as summary of the percentage of patients with worst on-treatment Division of Acquired Immunodeficiency Syndrome (DAIDS) grade laboratory abnormalities for selected analytes (Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total) with particular relevance to patients with HCV.

  • Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] [ Time Frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) ] [ Designated as safety issue: No ]

    This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total.

    In this outcome measure Haemoglobin is presented.


  • Changes From Baseline in Laboratory Test Values Over Time [ALT] [ Time Frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) ] [ Designated as safety issue: No ]

    This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total.

    In this outcome measure ALT is presented.


  • Changes From Baseline in Laboratory Test Values Over Time [AST] [ Time Frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) ] [ Designated as safety issue: No ]

    This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total.

    In this outcome measure AST is presented.


  • Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] [ Time Frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) ] [ Designated as safety issue: No ]

    This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total.

    In this outcome measure Bilirubin total is presented.



Enrollment: 119
Study Start Date: July 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 201335 for 24 weeks
BI 201335 once daily dose for 24 weeks in combination with PegIFN/RBV for 24 or 48 weeks
Drug: BI 201335
BI 201335 for 24 weeks
Drug: PegIFN/RBV
PegIFN/RBV for 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Chronic hepatitis C infection of GT-1 in patients who failed prior treatment with PegIFN and RBV in the 1220.7, 1220.30 and 1220.47 trials of the BI 201335 Phase III program.

  1. Patients from trials 1220.7, 1220.30 and 1220.47 of BI 201335 who have failed treatment with PegIFN/RBV in the placebo groups due to protocol-defined criteria of treatment failure (i.e. either non-response on treatment or relapse after end of treatment [EOT]).
  2. Patients must have received at least 4 weeks of assigned trial medication and been compliant with all study procedures.
  3. Female patients:

    • with documented hysterectomy,
    • who have had both ovaries removed,
    • with documented tubal ligation,
    • who are post-menopausal with last menstrual period at least 12 months prior to screening, or
    • 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 RBV 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 RBV.

    Medically accepted methods of contraception for females in this trial are ethinyl estradiol-containing contraceptives, diaphragm with spermicide substance, intra-uterine device and cervical cap.

    or

    Male patients:

    • who are documented to be sterile, or
    • who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (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. 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. 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).
  4. Signed informed consent form prior to trial participation.

Exclusion criteria:

  1. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an exclusion criteria.
  2. HIV co-infection
  3. Hepatitis B virus (HBV) infection based on presence of HBs-Ag
  4. 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)
  5. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months
  6. 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 patients ability to participate in this study
  7. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study.
  8. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 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.
  9. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to enrolment and throughout the treatment phase of this trial.
  10. Known hypersensitivity to any ingredient of the study drugs.
  11. 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).

Other exclusion criteria related to pegylated interferon and/or ribavirin restrictions are not listed here.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01330316

  Show 87 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01330316     History of Changes
Other Study ID Numbers: 1220.48, 2011-000141-20
Study First Received: April 5, 2011
Results First Received: July 3, 2015
Last Updated: July 3, 2015
Health Authority: Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Canada: Health Canada
France: Agence Nationale sécurité médicament et des produits santé
Germany: Federal Institute for Drugs and Medical Devices
Japan: Ministry of Health, Labor and Welfare
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
United Kingdom: Research Ethics Committee
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 27, 2015