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OpenTrials
Completed

NCT Number: NCT00774397

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

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.

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Key information

Conditions

Hepatitis C, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases Digestive System Diseases Disease Attributes Flaviviridae Infections Hepatitis Hepatitis C Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1220.5.5401 Boehringer Ingelheim Investigational Site, Capital Federal, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL >=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception

Exclusion criteria

Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value > 100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin > 1.5x ULN wiht ratio of direct/indirect >1. ALT or AST levels > 5x ULN INR prolonged to >1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.

Treatment and study plan

BI 201335 NA 240 mg QD / LI

Drug

240mg BI 201335 NA (Faldaprevir) once daily with a 3 days lead-in phase of PegIFN/RB, 24 weeks

Other names: Faldaprevir

PegIFN/RBV

Drug

PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks

BI 201335 NA 120mg QD / LI

Drug

120mg BI 201335 NA (Faldaprevir) once daily, for 24 weeks

Other names: Faldaprevir

BI 201335 NA 240 mg QD

Drug

240mg BI 201335 NA (Faldaprevir) once daily, 24 weeks

Other names: Faldaprevir

BI 201335 NA 240 mg BID

Drug

240mg BI 201335 NA (Faldaprevir) twice, 24 weeks

Other names: Faldaprevir

Placebo

Drug

Placebo

Primary outcomes

  1. Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo

    Time frame: 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'.

  2. Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy

    Time frame: 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 outcomes

  1. Virological Response at Week 2

    Time frame: Week 2

    Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (< 25 IU/ml, detectable or undetectable)

  2. Virological Response at Week 4

    Time frame: Week 4

    Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (< 25 IU/ml, detectable or undetectable)

  3. Early Virological Response (EVR)

    Time frame: 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

  4. Extended Rapid Virological Response (eRVR)

    Time frame: 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

  5. Complete Early Virological Response (cEVR)

    Time frame: Week 12

    Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12

  6. End of Treatment Response at Week 24

    Time frame: 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.

  7. End of Treatment Response at End of All Therapy

    Time frame: 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

  8. Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy

    Time frame: 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

  9. Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection

    Time frame: 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)

  10. Time to Loss of Virological Response

    Time frame: 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.

  11. Virological Rebound

    Time frame: 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.

  12. Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)

    Time frame: Up to Week 24

    Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout.

  13. Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)

    Time frame: Week 24 through Week 48

    Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout.

  14. Relapse

    Time frame: 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.

  15. Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo.

  16. Change From Baseline to Week 24 in Pulse Rate

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the administration of BI 201335 or placebo.

  17. Change From Baseline to Week 24 in Weight of the Patients

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the administration of BI 201335 or placebo.

  18. Global Assessment of Tolerability

    Time frame: 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'.

  19. Change From Baseline to Week 24 in Haemoglobin of the Patients

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the administration of BI 201335 or placebo.

  20. Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin

    Time frame: Baseline and Week 24

    Number of patients with normal or high baseline moved to low .

  21. Change From Baseline to Week 24 in Absolute Neutrophils of the Patients

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the administration of BI 201335 or placebo.

  22. Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils

    Time frame: Baseline and Week 24

    Number of patients with normal or high baseline moved to low .

  23. Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the drug administration of BI 201335 or placebo.

  24. Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT

    Time frame: Baseline and Week 24

    Number of patients with normal or low baseline moved to high .

  25. Change From Baseline to Week 24 in Total Bilirubin of the Patients

    Time frame: Baseline and Week 24

    Baseline is defined as the last value before the administration of BI 201335 or placebo.

  26. Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin

    Time frame: Baseline and Week 24

    Number of patients with normal or low baseline moved to high .

  27. Trough Concentration (Cpre,ss) of Faldaprevir at Steady State

    Time frame: 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.

  28. Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)

    Time frame: 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.

  29. Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)

    Time frame: 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.

  30. Trough Concentration (Cpre,ss) of PegIFN at Steady State

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Antiviral Effect, Safety and Pharmacokinetics of BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naïve and Treatment-experienced Patients for 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Double-blinded, Randomised, Placebo-controlled, Phase II)

Important dates

Study start
2008
Primary completion
2011
First posted
Oct 17, 2008
Registry last updated
Nov 16, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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