Clinical trial NCT01001754: Efficacy and Safety Study of PEG-rIL-29 Plus Ribavirin to Treat Chronic Hepatitis C Virus Infection
Official title: 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 Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
Hepatitis C, Chronic
PEGylated recombinant interleukin 29
PEG-interferon lambda
Interleukin 29
Virus
Infection
Liver Diseases
Lead sponsor: ZymoGenetics
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2009-10-27
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Interleukin 29 (IL-29) is a substance that is produced in the body to help fight viral infections. The purpose of this study is to evaluate the safety and antiviral effects of several different doses of PEG-rIL-29 (a man-made form of IL-29) when it is given in combination with daily oral doses of ribavirin (an antiviral drug) to subjects with hepatitis C infection who have received no prior treatment for this disease.

Detailed description: PEG-rIL-29 (also known as PEG-interferon lambda) is a unique Type III interferon molecule that has demonstrated antiviral activity when administered weekly for 4 weeks to treatment-relapsed and treatment-naive subjects with genotype 1 hepatitis C virus (HCV) infection. Because PEG-rIL-29 binds to a unique receptor with a more limited distribution than the receptor for interferon (IFN)-α, it may have the potential to treat HCV without some of the treatment-limiting side effects associated with IFN-α-based therapies. The purpose of this Phase 2a/b randomized, controlled, multicenter study is to compare the safety and efficacy of PEG-rIL-29 and peginterferon alfa-2a, both administered subcutaneously weekly for up to 48 weeks in combination with daily oral ribavirin, in treatment-naive subjects with chronic genotype 1, 2, 3, or 4 HCV infection. The initial part of the study (Phase 2a) will be conducted as an open-label study; the second part of the study (Phase 2b) will be conducted as a blinded study. The above information provided in this listing is specific to the Phase 2b portion of the study. In addition, two small open-label substudies will be conducted to evaluate the efficacy of 24-week treatment with PEG-rIL-29 and ribavirin in subjects with HCV genotype 1 who have a particular genetic polymorphism associated with favorable response (n=60) and to evaluate the efficacy of 16-week treatment with PEG-rIL-29 and ribavirin in subjects with HCV genotype 2 or 3 (n=30).

Eligibility criteria: Inclusion Criteria:

* 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
* HCV genotype 1, 2, 3, or 4
* HCV RNA ≥100,000 IU/mL
* ALT and AST ≤5.0 × ULN
* Documented absence of cirrhosis
* Able to comprehend the investigational nature of this study and sign an informed consent form

Exclusion Criteria:

* Mixed genotype HCV infection
* Current or prior history of decompensated liver disease
* Received any investigational drug, including a direct-acting antiviral agent, within 60 days prior to receiving study drug
* Positive test for hepatitis B surface antigen, human immunodeficiency virus (HIV)-1, or HIV2 antibody at screening
* Active substance abuse, such as alcohol, or inhaled or injected drugs, within 6 months

Additional inclusion and exclusion criteria are specified in the protocol.

Primary outcomes:
measure: HCV RNA
timeFrame: At week 12, week 24, or week 48
measure: Incidence and severity of adverse events
timeFrame: Through week 12, week 40, or week 48
Secondary outcomes:
measure: Incidence and severity of adverse events and laboratory abnormalities
timeFrame: Up to week 72
measure: HCV RNA
timeFrame: Up to week 72
measure: PD biomarkers
timeFrame: Up to week 72
measure: Quality of life assessments
timeFrame: Up to week 72
measure: Serum drug concentration profile
timeFrame: Up to week 48
Other outcomes:
Locations:
city: Beverly Hills
country: United States
state: California
city: Coronado
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Palm Springs
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Englewood
country: United States
state: Colorado
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Lutherville
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Newark
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Arlington
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Fairfax
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Herston
country: Australia
state: Queensland
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Clayton
country: Australia
city: Fitzroy
country: Australia
city: Fremantle
country: Australia
city: Greenslopes
country: Australia
city: Herston
country: Australia
city: Kogarah
country: Australia
city: Melbourne
country: Australia
city: Penrith
country: Australia
city: Perth
country: Australia
city: Westmead
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Wien
country: Austria
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Paris
country: France
city: Pessac
country: France
city: Bochum
country: Germany
city: Dusseldorf
country: Germany
city: Essen
country: Germany
city: Frankfurt/Main
country: Germany
city: Freiburg
country: Germany
city: Goettingen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Koln
country: Germany
city: Mainz
country: Germany
city: Munchen
country: Germany
city: Tubingen
country: Germany
city: Milano
country: Italy
city: Bialystok
country: Poland
city: Krakow
country: Poland
city: Lancut
country: Poland
city: Raciborz
country: Poland
city: Wroclaw
country: Poland
city: Santurce
country: Puerto Rico
city: Bucharest
country: Romania
city: Iasi
country: Romania
city: Timisoara
country: Romania
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Majadahonda
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: ZymoGenetics
name: Jan Hillson, MD
role: STUDY_DIRECTOR
References:
citation: Wang X, Hruska M, Chan P, Ahmad A, Freeman J, Horga MA, Hillson J, Kansra V, Lopez-Talavera JC. Derivation of Phase 3 dosing for peginterferon lambda-1a in chronic hepatitis C, Part 1: Modeling optimal treatment duration and sustained virologic response rates. J Clin Pharmacol. 2015 Jan;55(1):63-72. doi: 10.1002/jcph.363. Epub 2014 Jul 24.
citation: Hruska M, Wang X, Chan P, Ahmad A, Freeman J, Horga MA, Hillson J, Kansra V, Lopez-Talavera JC. Derivation of Phase 3 dosing for peginterferon lambda-1a in chronic hepatitis C, Part 2: Exposure-response analyses for efficacy and safety variables. J Clin Pharmacol. 2015 Jan;55(1):73-80. doi: 10.1002/jcph.361. Epub 2014 Jul 24.