A randomized (subjects chosen at random), double-blind (subject andinvestigator blind, sponsor open) placebo-controlled (some subjects will receive placebo) trial to evaluate the safety, tolerability and antiviralactivity of ACH-0141625 taken orally when combined with pegylated interferon alfa-2a and ribavirin, after 28 days dosing and after 12 weeks of dosing in subjects who have chronic hepatitis C.

Phase 1

Conditions: Hepatitis C Virus Genotype 1
MedDRA version: 14.0Level: LLTClassification code 10019751Term: Hepatitis C virusSystem Organ Class: 10022891 - Investigations
MedDRA version: 14.0Level: PTClassification code 10019744Term: Hepatitis CSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2010-022092-65-DE

Lead Sponsor: Achillion Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 0

Inclusion Criteria

1. Males and females aged 18 years or older
2. Chronic HCV infection, documented by one of the following:
• positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening, and positive for HCV RNA and anti-HCV antibody at the time of screening;
• or positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis).
3. HCV genotype 1 (including 1a, 1b or mixed 1a/1b); subjects with mixed genotypes (e.g. 1/2, 1/3, etc.) or other genotypes (e.g. 2, 3, 4, 5, or 6) will be excluded.
4. Females who are post-menopausal and amenorrheic must have an FSH measurement at screening with results in the post-menopausal range for the central laboratory. Females of childbearing potential or surgically sterilized females must have a negative pregnancy test at screening and baseline. Females must use a non-hormonal method of contraception and must agree not to get pregnant during the study and for six months following the discontinuation of standard of care.
5. Fertile males, defined as all males physiologically capable of fathering offspring, may be enrolled in this study. Males in this category must agree to use a condom and his female partner must agree to use one or more methods of contraception from the date of screening until 6 months after their last dose of RBV. Males must not donate sperm while enrolled in this study and for three months following the last exposure to RBV
6. Signed and dated written informed consent form
7. Willing to participate in all study activities (including the ability to safely self-inject study drug subcutaneously) and all study requirements (including effective contraception) during study period
8. Treatment naïve subjects
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Body Mass Index (BMI) > 36
2. Pregnant or nursing (lactating) females, confirmed by a positive hCG laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy.
3. Participation in any interventional clinical trial within previous 35 days.
4. History of participation in a clinical trial with a protease inhibitor or previous treatment with a protease inhibitor, where at least one dose of the protease inhibitor was consumed.
5. Use of herbal or homeopathic products, illicit drugs, CYP3A4/5 substrates, inducers or inhibitors (See Appendix 8), hormonal methods of contraception, corticosteroids, immunosuppressives, or cytotoxic agents within 28 days of first dose of study drug.
6. History of poor compliance with health and treatment regimens.
7. Have a clinically significant laboratory abnormality at screening:
• Absolute neutrophil count (ANC) <1,500 / mm2 (1.5 x 109/L)
• Platelets <90,000/mm2 (90 x 109/L)
• Hemoglobin <13 g/dL for males; <12 g/dL for females
• Serum creatinine > 1.5 x ULN or creatinine clearance < 50 mL/min; estimated by the Cockroft-Gault formula [(140-age) x weight (kg) / 72 x serum creatinine (mg/dL), if female multiply by 0.85].
• Total bilirubin > 1.2 mg/dL
* Segment 1: Serum alanine transaminase (ALT) > 2 x ULN
* Segment 2: (ALT) > 5 x ULN
* Segment 1: Serum aspartate aminotransferase (AST) > 2 x ULN
* Segment 2: (AST) > 5 x ULN
• Fasting serum glucose > 140 mg/dL and HbA1c > 7.5% (including diabetic subjects on medication) or new onset diabetes.
• Abnormal thyroid stimulating hormone (TSH) of >1.2 ULN, or unstable thyroid disease.
• Alpha fetoprotein (AFP) > 20 ng/mL unless a liver imaging study (CT or MRI) shows no clinically significant lesions within 6 months prior to the Baseline visit.
8. Known HIV-1 or HIV-2 infection/serology
9. Positive Hepatitis B Surface Antigen (HBsAg)
10.
Segment 1: Subjects with any history of decompensated liver disease defined as cirrhotic subjects with a Child-Pugh score of = 7. Decompensated liver disease includes the presence of ascites, variceal bleeding, hepatic encephalopathy, or other signs of progressive portal hypertension or progressive hepatic insufficiency (based on fibroscan or liver biopsy).
Segment 2: Subjects who have had a liver biopsy that shows bridging fibrosis or cirrhosis (Metavir >3, Ishak >4).
11. Nonalcoholic steatohepatitis (NASH) if ballooning degeneration or Mallory bodies are present on liver biopsy.
12. Other forms of liver disease (e.g. alcoholic, autoimmune, biliary, Wilson’s, Gilbert’s, Dubin Johnson, and Crigler Najjar syndromes).
13. Subjects who prematurely discontinued, interrupted, or dose reduced prior PegIFN-alfa and RBV therapy, due to noncompliance or safety and/or tolerability issues.
14. Encephalopathy or altered mental status of any etiology
15. History of moderate, severe or uncontrolled psychiatric disease (e.g. depression, including a history of hospitalization or prior suicidal attempt), bipolar disease, schizophrenia, or personality disorder. Subjects with a history of mild, stable depression may be considered provided that a pretreatment assessment (including a depression scale, BDI-II or HADS) of the subject’s affective status supports that the subject is clinically stable. Subjects with a score that is elevated (greater than 29 for BDI-II, 7 for HADS) will require further clinical evaluation for depression prior to inclusion into the study. T

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

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