Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced

NCT00793793 | Completed Phase 1 Results

• 2 other identifiers: 1220.22007-001158-19
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 16

Brief Summary

This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA combination therapy with PegIFN/RBV for treatment-experienced patients. A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (4)

• Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients)

  Efficacy endpoint: VR (virologic response) of \>=2 log10 reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) from baseline at any time up to Day 14 (naïve patients) or Day 28 (experienced patients).

  Baseline and up to 4 weeks

• Occurrence of Adverse Events (AEs) During BI201335 + Washout Period

  Occurrence of Adverse Events (AEs) during BI201335 + washout period. For placebo patients include all AEs through 30 days after trial discontinuation.

  from day 1 and up to 4 weeks + 4 days washout

• Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period

  Occurrence of Serious Adverse Events (SAEs)during BI201335 or BI201335+ washout period. For placebo patients include all SAEs through 30 days after trial discontinuation.

  from day 1 and up to 4 weeks + 4 days washout

• Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time

  Occurrence of laboratory test abnormalities and with respect to Division of AIDS (DAIDS) classification and laboratory test values change over time. ALT=Alanine transaminase (SGPT), AST=Aspartate transaminase (SGOT).

  Baseline and up to 4 weeks

Secondary Outcomes (29)

• Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients

  Baseline and up to 4 weeks

• Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients

  Baseline and up to 4 weeks

• Rapid Virologic Response (RVR)

  week 4

• Early Virologic Response (EVR)

  week 12

• Complete EVR1 (cEVR1)

  week 4 and week 12

Study Arms (5)

20mg

EXPERIMENTAL

patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Drug: BI201335

48mg

EXPERIMENTAL

patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Drug: BI201335

120mg

EXPERIMENTAL

patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Drug: BI201335

240mg

EXPERIMENTAL

patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days

Drug: BI201335

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI201335 DRUG

patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days

240mg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection
• b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load \>= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

You may not qualify if:

• Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
• Evidence of liver disease due to causes other than chronic HCV infection
• Positive ELISA for HIV-1 or HIV-2
• Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
• Any previous liver biopsy consistent with cirrhosis
• Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy
• Haemophilia
• Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
• Severe pre-existing psychiatric disease
• Poorly controlled diabetes mellitus
• Ischaemic heart disease
• Chronic obstructive airway disease
• Autoimmune disease; including autoimmune hepatitis
• History of alcohol abuse within the past 12 months
• Hyperbilirubinemia (conjugated bilirubin) \>1.5x ULN

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (16)

1220.2.10 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Location

1220.2.15 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Location

1220.2.17 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

Location

1220.2.11 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1220.2.12 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1220.2.14 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Location

1220.2.3304A Boehringer Ingelheim Investigational Site

Lyon, France

Location

1220.2.3303A Boehringer Ingelheim Investigational Site

Marseille, France

Location

1220.2.3301A Boehringer Ingelheim Investigational Site

Paris, France

Location

1220.2.3302A Boehringer Ingelheim Investigational Site

Paris, France

Location

1220.2.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1220.2.49005 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1220.2.49006 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1220.2.49004 Boehringer Ingelheim Investigational Site

Kiel, Germany

Location

1220.2.49003 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1220.2.34001 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

Related Publications (2)

• Berger KL, Lagace L, Triki I, Cartier M, Marquis M, Lawetz C, Bethell R, Scherer J, Kukolj G. Viral resistance in hepatitis C virus genotype 1-infected patients receiving the NS3 protease inhibitor Faldaprevir (BI 201335) in a phase 1b multiple-rising-dose study. Antimicrob Agents Chemother. 2013 Oct;57(10):4928-36. doi: 10.1128/AAC.00822-13. Epub 2013 Jul 22.

  PMID: 23877706 DERIVED

• Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, White PW, Stern JO, Steinmann G, Yong CL, Kukolj G, Scherer J, Boecher WO. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011 Jun;54(6):1114-22. doi: 10.1016/j.jhep.2010.08.040. Epub 2010 Nov 11.

  PMID: 21145839 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

faldaprevir

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Additional secondary endpoints were listed in the original protocol. Those endpoints are of exploratory nature only and were not considered relevant for trial conclusions. For more information see tab "Full Text Review", section "More Information".

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2008
• First Posted: November 19, 2008
• Study Start: September 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 25, 2011
• Last Updated: September 5, 2018
• Results First Posted: September 17, 2015

Record last verified: 2018-08

Locations

DE (5); FR (4); ES (1); US (6)