Brief Summary
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24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.
Brief Title
A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hepatitis C
Eligibility 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.
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.
Inclusion 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.
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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
18 Years
NCT Id
NCT01330316
Org Class
Industry
Org Full Name
Boehringer Ingelheim
Org Study Id
1220.48
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL
Outcome Time Frame
12 weeks post treatment, up to 60 weeks
Secondary Ids
Secondary Id
2011-000141-20
Secondary Outcomes
Outcome Description
Sustained virologic response 24 weeks, defined as a plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.
Outcome Time Frame
24 weeks post treatment, up to 72 weeks
Outcome Measure
Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)
Outcome Description
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.
Outcome Time Frame
week 4 and week 8
Outcome Measure
Early Treatment Success (ETS)
Outcome Description
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.
Outcome Time Frame
Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Outcome Measure
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT)
Outcome Description
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.
Outcome Time Frame
48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS
Outcome Measure
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment.
Outcome Description
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.
Outcome Time Frame
Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers.
Outcome Measure
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT)
Outcome Description
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.
Outcome Time Frame
Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Outcome Measure
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment.
Outcome Description
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.
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.
Outcome Time Frame
from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Outcome Measure
Occurrence of Adverse Events (Overall and by DAIDS Grade)
Outcome Description
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.
Outcome Time Frame
from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Outcome Measure
Occurrence of Adverse Events Leading to Treatment Discontinuation
Outcome Description
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.
Outcome Time Frame
from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Outcome Measure
Occurrence of Serious Adverse Events (SAEs)
Outcome Description
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.
Outcome Time Frame
from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Outcome Measure
Occurrence of Drug-related AEs as Assessed by the Investigator
Outcome Description
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.
Outcome Time Frame
baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study
Outcome Measure
Laboratory Test Abnormalities by DAIDS Grades
Outcome Description
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.
In this outcome measure Haemoglobin is presented.
Outcome Time Frame
baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Outcome Measure
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin]
Outcome Description
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.
In this outcome measure ALT is presented.
Outcome Time Frame
baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Outcome Measure
Changes From Baseline in Laboratory Test Values Over Time [ALT]
Outcome Description
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.
In this outcome measure AST is presented.
Outcome Time Frame
baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Outcome Measure
Changes From Baseline in Laboratory Test Values Over Time [AST]
Outcome Description
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.
In this outcome measure Bilirubin total is presented.
Outcome Time Frame
baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Outcome Measure
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total]
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Gaglio
Investigator Email
PGAGLIO@montefiore.org
Investigator Phone