Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)

Phase 2

Completed

Conditions: Hepatitis C, Chronic

Interventions: Drug: BI 201335 NA 120mg QD / LI
Drug: PegIFN/RBV
Drug: BI 201335 NA 240 mg QD
Drug: BI 201335 NA 240 mg QD / LI
Drug: BI 201335 NA 240 mg BID
Drug: Placebo

Registration Number: NCT00774397

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 719

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
120 mg QD / LI-TN	BI 201335 NA 120mg QD / LI	120 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients
Placebo	PegIFN/RBV	Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
240 mg QD TN	BI 201335 NA 240 mg QD	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
240 mg QD / LI-TN	BI 201335 NA 240 mg QD / LI	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
240 mg QD / LI-TN	PegIFN/RBV	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
240 mg QD TE	PegIFN/RBV	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
240 mg QD TE	BI 201335 NA 240 mg QD	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
240 mg QD / LI-TE	PegIFN/RBV	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients
240 mg QD TN	PegIFN/RBV	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
Placebo	Placebo	Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
120 mg QD / LI-TN	PegIFN/RBV	120 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients
240 mg QD / LI-TE	BI 201335 NA 240 mg QD	240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients
240 mg BID / LI-TE	BI 201335 NA 240 mg BID	240mg BI 201335 NA (Faldaprevir) twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
240 mg BID / LI-TE	PegIFN/RBV	240mg BI 201335 NA (Faldaprevir) twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients

Primary Outcome Measures

Name	Time	Method
Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo	Week 28	An achieved virological response is defined as the plasma Hepatitis C Virus RiboNucleic Acid (HCV RNA) level below the lower limit of detection (BLD). This data was only collected for patients, who stopped trial participation at Week 24 and did not continue with PegIFN/RBV until Week 48. The lower limit of quantification (BLQ) of this assay was 25 IU/mL and the lower limit of detection (BLD) was 10 IU/mL at the time of the protocol finalisation. During the course of the trial, the manufacturer defined BLD as '\< 25 IU/mL, not detectable' and BLQ as '\< 25 IU/mL, detectable'.
Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy	Day 155 after the end of all treatment	Virological (VL) response was defined as the plasma HCV RNA level below the lower limit of detection. The first VL measurement that occurred in the time window ≥ Day 155 (from End Of Treatment on) was selected for the determination of SVR24. Therefore, patients with virological load BLD 24 weeks after completion of therapy, who had a rebound after this time point (outside the defined time window of 155 days after end of all treatments) were identified as SVR24 achieved.

Secondary Outcome Measures

Name	Time	Method
Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)	Up to Week 24	Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout.
Global Assessment of Tolerability	Week 24	The investigator was to assess the tolerability of trial medication based on adverse events (AEs) and the laboratory evaluation. Tolerability was assessed by the investigator according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin	Baseline and Week 24	Number of patients with normal or high baseline moved to low .
Change From Baseline to Week 24 in Absolute Neutrophils of the Patients	Baseline and Week 24	Baseline is defined as the last value before the administration of BI 201335 or placebo.
Trough Concentration (Cpre,ss) of Faldaprevir at Steady State	Week 8, week 10, week 12, week 24	C(pre,ss) is defined as pre-dose (trough) concentration of Faldaprevir in plasma at steady state immediately before administration of the next dose.
Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)	Week 24 through Week 48	Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout.
Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure	Baseline and Week 24	Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo.
Change From Baseline to Week 24 in Haemoglobin of the Patients	Baseline and Week 24	Baseline is defined as the last value before the administration of BI 201335 or placebo.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT	Baseline and Week 24	Number of patients with normal or low baseline moved to high .
Change From Baseline to Week 24 in Total Bilirubin of the Patients	Baseline and Week 24	Baseline is defined as the last value before the administration of BI 201335 or placebo.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin	Baseline and Week 24	Number of patients with normal or low baseline moved to high .
Virological Response at Week 4	Week 4	Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (\< 25 IU/ml, detectable or undetectable)
Time to Loss of Virological Response	Week 24	Time to loss of virological response, defined as the last value below the lower limit of detection in a patient who subsequently had 2 consecutive plasma HCV RNA level measurements ≥100 IU/mL. Patients that did not achieve suppression of plasma HCV RNA levels below the lower limit of detection until Week 24 were defined as having a time to failure of zero. Time is expressed in Median number of days.
Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)	Week 8, week 10, week 12, week 24	C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Complete Early Virological Response (cEVR)	Week 12	Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12
End of Treatment Response at Week 24	Week 24	End of Treatment Response of BI 201335 or placebo (ETR BI 201335/placebo ) is defined as plasma HCV RNA level below the lower limit of detection at Week 24.
Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection	On or after day 155 post end of all treatment	Summary of time (i.e Median number of days) to reach a plasma HCV RNA level below limit of detection (BLD)
Relapse	post-End of treatment (i.e. post 48 weeks)	Relapse was rebound after the viral load at end of all treatment had been below the lower limit of detection, or, if the value at end of all treatment was missing, after both the last value before End of Treatment (EOT) and the first value after End of Treatment were below the lower limit of detection. Patients could experience relapse at any point post-treatment.
Change From Baseline to Week 24 in Pulse Rate	Baseline and Week 24	Baseline is defined as the last value before the administration of BI 201335 or placebo.
Change From Baseline to Week 24 in Weight of the Patients	Baseline and Week 24	Baseline is defined as the last value before the administration of BI 201335 or placebo.
Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients	Baseline and Week 24	Baseline is defined as the last value before the drug administration of BI 201335 or placebo.
Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)	Week 8, week 10, week 12, week 24	C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Trough Concentration (Cpre,ss) of PegIFN at Steady State	Week 8, week 10, week 12, week 24	C(pre,ss) is defined as pre-dose (trough) concentration of PegIFN in plasma at steady state immediately before administration of the next dose.
Virological Response at Week 2	Week 2	Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (\< 25 IU/ml, detectable or undetectable)
Early Virological Response (EVR)	Baseline and Week 12	Early Virological Response (EVR) is defined as ≥ 2 log 10 reduction in plasma HCV RNA level from baseline at Week 12
Extended Rapid Virological Response (eRVR)	Week 4 and Week 12	Extended Rapid Virological Response (eRVR) is defined as plasma HCV RNA levels below the lower limit of quantification at Week 4 and below the lower limit of detection at Week 12
End of Treatment Response at End of All Therapy	Week 24 or Week 48	End of Treatment Response (ETR) is defined as plasma HCV RNA level below the lower limit of detection at end of all therapy, i.e. at Week 24 or Week 48
Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy	Week 36 or Week 60	Sustained Virological Response 12 Weeks (SVR12) after completion of all therapy is defined as plasma HCV RNA level below the lower limit of detection at 12 weeks after completion of all therapy, i.e. at Week 36 or 60
Virological Rebound	Week 24 or Week 48	Virological rebound is defined as increase of ≥ 1 log 10 in plasma HCV RNA level from a quantifiable nadir, or to ≥ 250 IU/mL after previous nadir \< 25 IU/mL (detectable), or to ≥ 100 IU/mL after a previous viral load below the lower limit of detection. Note that this is numerical rebound, not requiring confirmation with a re-measurement.
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils	Baseline and Week 24	Number of patients with normal or high baseline moved to low .

Trial Locations

Locations (100): 1220.5.0001 Boehringer Ingelheim Investigational Site
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San Francisco, California, United States
1220.5.0008 Boehringer Ingelheim Investigational Site
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San Francisco, California, United States
1220.5.0005 Boehringer Ingelheim Investigational Site
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Chicago, Illinois, United States
1220.5.0006 Boehringer Ingelheim Investigational Site
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Lutherville, Maryland, United States
1220.5.0002 Boehringer Ingelheim Investigational Site
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New York, New York, United States
1220.5.0003 Boehringer Ingelheim Investigational Site
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New York, New York, United States
1220.5.0007 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1220.5.0010 Boehringer Ingelheim Investigational Site
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Germantown, Tennessee, United States
1220.5.0009 Boehringer Ingelheim Investigational Site
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Nashville, Tennessee, United States
1220.5.0004 Boehringer Ingelheim Investigational Site
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Austin, Texas, United States
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1220.5.0001 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States