Safety, antiviral effect and pharmacokinetics of BI 207127 in combination with BI 201335 and with or without ribavirin for 4, 16, 24, 28 or 40 weeks in patients with chronic HCV genotype 1 infection (randomized Phase Ib/II)
- Conditions
- chronic hepatitis C infection of genotype 1MedDRA version: 17.1Level: LLTClassification code 10019751Term: Hepatitis C virusSystem Organ Class: 100000004848Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2009-018197-66-PT
- Lead Sponsor
- nilfarma, Lda.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 401
1)Chronic hepatitis C infection, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening, or by a liver biopsy typical of chronic hepatitis C in combination with positive HCV serology
2)HCV infection of genotype 1 (1a or 1b) confirmed by genotypic testing at screening. Note: if central lab is unable to differentiate the subtype, a recent subtyping from local lab within 6 months prior to screening will be accepted for stratification.
3)Treatment naive, defined as no prior treatment with any interferon, pegylated interferon, and /or ribavirin and no prior treatment with at least one dose of any direct antiviral agent for acute or chronic hepatitis C infection
4)Plasma HCV RNA = 100,000 IU/mL at screening
5)Liver biopsy within two years or fibroscan within six months prior to screening. Note: In Part 1, cirrhosis has to be excluded, whereas in Part 2, Part 3 patients with Child-Pugh A cirrhosis are eligible. Fibrosis stage (according to biopsy or fibroscan) has to be documented.
6)Age 18 – 75 years
7)Female patients who are infertile or who are of childbearing potential with a negative pregnancy test at screening and on Day 1 (Visit 2), that either agree to abstain from intercourse, or agree to use two non-hormonal methods of birth control from the date of screening until 7
months after the last dose of ribavirin. Accepted methods of contraception in the study include diaphragm with a spermicidal substance, cervical caps, intrauterine devices and condoms. Note: Systemic hormonal contraceptives may not be as effective in women taking BI 207127/BI 201335 combination therapy and are not accepted
methods of contraception in this study.
Patients must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin, OR
Male patients who are sterile, or who agree to abstain from intercourse or who use a condom while their female partners use one medically accepted method of birth control
8)Signed informed consent form prior to trial participation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 51
1) Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) or mixed subgenotype 1a/b diagnosed by genotypic testing at screeningdiagnosed by genotypic testing at screening
2) Evidence of liver disease due to causes other than chronic HCV infection
3) Positive ELISA for HIV-1 or HIV-2
4) Hepatitis B virus (HBV) infection based on presence of HBs-Ag
5) Decompensated liver disease, or history of decompensated liver disease
6) Active or suspected malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)
7) Patients with ongoing or historical photosensitivity or recurrent rash
8) History of alcohol or drug abuse (except cannabis) within the past 12 months
9) Body mass index <18 or > 35 kg/m2
10) Usage of any investigational drugs within 30 days prior to randomisation, or 5 half-lives, whichever is longer; or the planned usage of an investigational drug during the course of the current study
11) Known hypersensitivity to any ingredient of the study drugs
12) A condition that is defined as one which in the opinion of the investigator may either interfere with the patient’s capability for participation in the trial or may influence the results of the trial or the patient’s ability to participate in the trial.
13) 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 an appropriate imaging study within 6 months prior to randomisation
14) Total bilirubin > 1.5 x ULN with ratio of direct/indirect > 1
15) AST or ALT > 5 x ULN
16) Prothrombin time INR (International Normalised Ratio) prolonged to >1.5 x ULN
17) Requirement for chronic systemic corticosteroids (nasal or pulmonary steroids will be allowed)
18) Received concomitant systemic antiviral, hematopoietic growth factor, or
immunomodulatory treatment with 30 days prior to randomisation or 5 half-lives,
whichever is longer; patients being treated with oral antivirals such as acyclovir,
famcyclovir, valcyclovir for mild, localised recurrent herpes simplex infection, or
with oseltamivir and zanamivir for Influenza A may be enrolled.
19) Received silymarin (milk thistle) or glycyrrhizin or Sho-saiko-to (SST) within 30 days prior to randomisation
20) Use of any of the medications listed in Appendix 10.2 within 30 days prior to randomisation
21) Hemoglobin <12.0g/dL for women and <13.0g/dL for men
22) Serum albumin =3.6 g/dL
23) White blood cell count <2,000 cells/mm3
24) Absolute neutrophil count < 1,500 cells/mm3
25) Platelet count < 100,000 /mm3
26) Creatinine > 1xULN or creatinine clearance =50 ml/min
27) HbA1c > 7.5%
28) TSH and T4 outside normal limits (accepted if thyroid function adequately
controlled)
29) Chronic obstructive pulmonary disease
30) Screening ECG with any abnormalities suggestive of prior or active
cardiovascular disease
31) Chronic cardiac disease (e.g., coronary artery disease, congestive heart failure,
uncontrolled hypertension, significant arrhythmia)
32) Autoimmune disease, including autoimmune hepatitis
33) Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
34) Glucose-6-phosphate dehydrogenase deficiency
35) History of moderate, severe or uncontrolled psychiatric disease, especially
depression, including a history of hospitalization or prior suicidal attempt
36) Abnormal find
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method