Randomized, Controlled Phase 2a/b Study of the Efficacy and Safety of PEG-rIL-29 Administered in Combination with Ribavirin to Treatment-Naive Subjects with Chronic Hepatitis C Virus Infectio

• Conditions: Chronic Hepatitis C Virus Infection; MedDRA version: 14.0Level: LLTClassification code 10008912Term: Chronic hepatitis CSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2009-011786-80-DE
• Lead Sponsor: ZymoGenetics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-11
• Last Update Posted: 24 November 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Males or females between the ages of 18 and 70 years, inclusive, at the time of signing informed consent
2. No prior therapy for chronic HCV, other than up to 2 weeks of single-agent therapy with a direct-acting antiviral agent, including but not limited to, a protease or polymerase inhibitor
3. Genotype 1, 2, 3, or 4 HCV RNA. Mixed genotype HCV infection is not allowed
4. HCV RNA =100,000 IU/mL
5. ALT and AST =5.0 × ULN
6. Documented absence of cirrhosis, with the exception of approximately 10 subjects per treatment group in Phase 2b. For subjects without cirrhosis, absence of cirrhosis must be documented as follows: genotype 1 and 4 subjects must have a documented liver biopsy performed =2 years before study randomization. Genotype 2 and 3 subjects must have either a documented liver biopsy performed =2 years before study randomization or a FibroTest performed during the screening period. Subjects without cirrhosis must have a documented liver biopsy with an Ishak score =4 or Metavir fibrosis score
=3 (genotypes 1, 2, 3 or 4), or a FibroTest =0.72 (genotypes 2 or 3). Subjects with cirrhosis must have a documented liver biopsy with an Ishak fibrosis score of =5 or a Metavir fibrosis score of 4. Subjects with cirrhosis must not have decompensated liver disease.
7. No prior history of hepatocellular carcinoma at any time, nor evidence of hepatocellular carcinoma documented by abdominal imaging (e.g., ultrasound), within 12 months of study randomization; imaging may be performed during screening period. 8. Alpha-fetoprotein <100 ng/mL
9. ECG with no clinically significant abnormalities at the time of screening as deemed by the investigator
10. Platelet count =90,000/mm3; ANC =1500/mm3; hemoglobin (Hgb) =12 g/dL (males) or =11 g/dL (females)
11. Partial thromboplastin time (PTT) =1.5 × ULN; fibrinogen = lower limit of normal (LLN)
12. Creatinine clearance =50 mL/min calculated according to the Cockcroft-Gault equation
13. Thyroid-stimulating hormone (TSH) and/or T4 within 0.8 to 1.2 times the normal limit, or adequately controlled thyroid function as assessed by the investigator
14. Documented baseline retinal exam performed =1 year of study randomization. For subjects with diabetes, hypertension, or other risk factors for retinal disease per assessment of the investigator, the exam should be performed by an ophthalmologist; may be performed during screening period
15. Able to comprehend the investigational nature of this study and sign an institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form
16. If female and of child-bearing potential, has a negative serum pregnancy
test at screening and a negative serum or urine pregnancy test within 24
hours before initial study drug treatment. For the purpose of this study, a
female subject should be considered of childbearing potential unless she is
documented as surgically sterile (i.e., by hysterectomy, bilateral oophorectomy, or medically documented ovarian failure), postmenopausal for at least 2 years, or if postmenopausal for =2 years, has folliclestimulating hormone (FSH) >35 mIU/mL
17. If male, or female of child-bearing potential must agree to utilize 2 separate forms of contraception, one of which must be an effective barrier method (or be nonheterosexually active or have a vasectomized partner with documented
azospermia) from the time of signing informed consent until 6 months after the
last dose of ribavirin

Exclusion Criteria

1. Mixed genotype HCV infection
2. Current or prior history of decompensated liver disease, including any of the following: current or prior history of encephalopathy of any grade, current or prior history of variceal bleeding, current or prior history of ascites, total serum bilirubin >1. 5 mg/dL (unless due to Gilbert’s disease), albumin 1.2
3. Currently lactating or breast-feeding
4. Has a female partner who is pregnant
5. Received any investigational drug, including a direct-acting antiviral agent, within 60 days prior to receiving study drug
6. Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
7. Current systemic use of immunosuppressive medications, including corticosteroids
8. Current use of heparin or coumadin
9. Positive test for hepatitis B surface antigen, human immunodeficiency virus (HIV)-1, or HIV2 antibody at screening
10. Active substance abuse, such as alcohol, or inhaled or injected drugs, within 6 months before signing informed consent. Subjects who are receiving methadone or other substitutive product under medical supervision are eligible. Use of marijuana for medical purposes is allowed.
11. Received blood products within 30 days prior to study randomization
12. Use of hematologic growth factors within 90 days prior to study randomization
13. Prior or current history of cardiomyopathy, ischemic cardiac disease, or cerebrovascular disease. Patients with a history of angioplasty, stent placement, or other revascularization procedures are excluded.
14. Prior or current history of clinically significant hemoglobinopathy or hemolytic anemia 15. Prior history of clinically significant liver disease other than chronic hepatitis C infection
16. Prior or current history of interstitial lung disease or sarcoidosis
17. History of organ transplant; prior corneal transplant is permitted
18. History of immunologically mediated disease (including, but not limited to, rheumatoid arthritis, inflammatory bowel disease, moderate to severe psoriasis [mild psoriasis is allowed], sarcoidosis, and systemic lupus erythematosus)
19. History of moderate, severe, or uncontrolled psychiatric disease; mild depression controlled at time of study entry is allowed
20. Active seizure disorder. Subjects with a seizure history on anti-seizure medication and with no seizure during the year prior to signing informed consent are allowed
21. Any other known contraindication to peginterferon alfa-2a or ribavirin therapy
22. Systemic antibiotics, antifungals, or antivirals for treatment of active infection within 14 days of enrollment
23. Currently on dialysis, including hemodialysis or peritoneal dialysis
24. Has, in the opinion of the investigator, any physical exam findings, laboratory abnormalities, or other medical, social, or psychosocial factors that may negatively impact compliance or subject’s safety by participation in this study; this should include conditions which may affect hematologic parameters, for example, prior or current history of porphyria cutanea tarda and/or hemophilia.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified