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

• Conditions: Chronic Hepatitis C Virus Infection; MedDRA version: 12.0Level: LLTClassification code 10008912Term: Chronic hepatitis C

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-25
• Last Update Posted: 20 March 2012

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 in
each treatment group in Phase 2b. Subjects with cirrhosis must not have decompensated liver disease. 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 (genotype 2 or 3)
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. PTT =1.5 × ULN; fibrinogen = lower limit of normal
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 72 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 follicle-stimulating 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) from the time of signing
informed consent until 6 months after the last dose of ribavirin. Medically
accepted contraception methods include intrauterine device; barrier methods, such
as diaphragm, condom, cap or sponge, used with a spermicide; or hormonal
contraception. Female subjects who use hormonal contra

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 <3.5 g/dL, or INR >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 or significant ischemic cardiac or
cerebrovascular disease, including history of angina, myocardial infarction, or
cerebrovascular accident, within 12 months of study enrollment
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

Study & Design

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