Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Chronic Hepatitis C Virus Infection

Boehringer Ingelheim

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hepatitis C, Chronic

Treatments: Drug: BILN 2061 W, medium dose; Drug: Placebo; Drug: BILN 2061 W, low dose; Drug: BILN 2061 W, high dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02226952

605.5

Details and patient eligibility

About

Study to assess the antiviral efficacy, pharmacokinetics and tolerability of BILN 2061 ZW in a polyethyleneglycol 400 (PEG 400: ethanol) drinking solution given for two days bid in patients with chronic Hepatitis C Virus (HCV) infection.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female or male sex, age of 18 years or older
• Active, chronic Hepatitis C virus (HCV) infection
• Liver biopsy consistent with active HCV infection obtained within the last 12 months
• Written informed consent consistent with International Committee on Harmonization (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study procedures
• HCV of genotype I (Group 1, 2, 4 and 5) and non-genotype 1 (Group 3)
• HCV load greater than 50,000 copies messenger ribonucleic acid (mRNA) per ml serum at screening
• For Group 5 only: Histology showing moderate or severe fibrosis (portal fibrosis, septae, periportal and porto-central septae), no regenerative nodes and no incomplete or complete cirrhosis, corresponding to Ishak score 3 or 4, or Metavir F2 or F3 (if Ishak is not 5)

Exclusion criteria

• Women of childbearing potential or breastfeeding women. Postmenopausal women less than 6 months after last menses, surgically sterilized or hysterectomised patients less than 3 months after operation or without a negative serum pregnancy test

• Males not using an adequate form of contraception (condom, sterilisation at least 6 months post operation) if their partner is of childbearing potential (criteria see above) and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/ implantable, intra-uterine device (IUD))

• Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis

• Ascites or other current evidence of portal hypertension

• Histology showing signs of bridging or higher grade fibrosis (e.g. Fibrosis >= Grade 3 (Ishak score) or >= 2 (Metavir score) for treatment groups 1, 2, 3, 4 or for Treatment group 5: Histology showing less than moderate or severe fibrosis (portal fibrosis, septae, periportal and porto-central septae), or showing regenerative nodes or incomplete or complete cirrhosis, corresponding to other Ishak scores than 3 or 4 and to other Metavir scores than F2 or F3 (or F3 and Ishak 5)

• History of abuse of alcohol within the past twelve months

• Planned or concurrent usage of any other pharmacological therapy at screening, including any antiviral therapy

• Any concurrent infectious disease requiring antimicrobial treatment

• History of malignancy (except for previously cured squamous cell or basal cell carcinoma)

• Usage of any investigational drug within thirty (30) days prior to enrolment; or the planned usage of an investigational drug during the course of the current study

• Known hypersensitivity to drugs

• Inability to comply with the protocol

• Prior randomization into this trial

• Child´s B or C liver diseases at screening (treatment groups 1, 2, 3, 4). Applicable for treatment group 5 only:

  • For Bilirubin - refer to following exclusion criterion
  • Quick (Prothrombin time) < 70%
  • Albumin < 3.5 g/dl
  • Clinical evidence of ascites
  • Clinical evidence of encephalopathy

• Clinically apparent jaundice or a total bilirubin or alkaline phosphatase (AP) exceeding 1.5 x upper limit of normal (ULN) at screening (treatment groups 1, 2, 3, 4). Treatment group 5 (BILN 2061 ZW, 200 mg bid/2 days in patients with advanced liver fibrosis): Clinically apparent jaundice or a bilirubin >= 2.0 mg/dl at screening. Increased alkaline phosphatase (AP) is allowed.

• ALT or AST > 5 x ULN at screening (treatment groups 1, 2, 3, 4). Treatment group 5: ALT or AST >= 10 x ULN at screening

• A platelet count of less than 100.000 platelets per mm3 at screening

• White blood cell count of less than 2,000 cells per mm3 at screening

• Positive test for human immunodeficiency Virus (HIV) at screening

• Positive test for illicit or unprescribed drugs or medications at screening. Positive test for cannabis may be allowed if the investigator assesses this result not as clinically significant

• Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

51 participants in 6 patient groups, including a placebo group

Group 1

Experimental group

Description:

BILN 2061 W, medium dose, in patients with genotype 1, minimal fibrosis

Treatment:

Drug: BILN 2061 W, medium dose

Group 2

Experimental group

Description:

BILN 2061 W, high dose, in patients with genotype 1, minimal fibrosis

Treatment:

Drug: BILN 2061 W, high dose

Group 3

Experimental group

Description:

BILN 2061 W, high dose, in non-genotype 1 patients, minimal fibrosis

Treatment:

Drug: BILN 2061 W, high dose

Group 4

Experimental group

Description:

BILN 2061 W, low dose, in patients with genotype 1, minimal fibrosis

Treatment:

Drug: BILN 2061 W, low dose

Group 5

Experimental group

Description:

BILN 2061 W, medium dose, in patients with genotype 1, advanced fibrosis

Treatment:

Drug: BILN 2061 W, medium dose

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo