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480 STUDY: Phase 2b Study of Locteron Plus Ribavirin to Treat Hepatitis C Virus (HCV) (480S)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biolex Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00953589
First received: August 5, 2009
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

The purpose of this 12-week study was to assess in subjects with chronic hepatitis C (treatment-naïve, genotype 1) receiving weight-based doses of ribavirin the early virologic response to the 480 ug dose level of Locteron™, dosed every 2 weeks, in comparison with 1.5 ug/kg PEG-Intron™ dosed weekly.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 480 STUDY: Phase 2b Open-label, Randomized Study in Treatment Naïve Subjects With HCV G1 to Compare the Efficacy, Safety, and Tolerability of the 480 µg Dose of Locteron™ Plus Ribavirin Given Bi-Weekly to PEG-Intron™ Plus Ribavirin Given Weekly

Resource links provided by NLM:


Further study details as provided by Biolex Therapeutics, Inc.:

Primary Outcome Measures:
  • Primary efficacy endpoint: EVR: the proportion of subjects in each arm that have at least a 2 log drop in HCV RNA from Baseline [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • the proportion of subjects in each arm demonstrating HCV RNA undetectable (< 10 IU/mL) after 12 weeks of randomized treatment [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Enrollment: 74
Study Start Date: July 2009
Study Completion Date: January 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Locteron ® PANEL A
PANEL A: Locteron™ 480 µg dosed every 2 weeks in two subcutaneous injections (160 µg and 320 µg)
Drug: ribavirin
Ribavirin - oral administration Subjects with body weight < 65 kg: 800 mg/day Subjects with body weight 65-85 kg: 1000 mg/day Subjects with body weight 86-105 kg: 1200 mg/day Subjects with body weight > 105 kg: 1400 mg/day
Other Name: Ribasphere
Experimental: Locteron ® PANEL B
PANEL B: Locteron™ 480 µg dosed every two weeks in single subcutaneous injections
Drug: ribavirin
Ribavirin - oral administration Subjects with body weight < 65 kg: 800 mg/day Subjects with body weight 65-85 kg: 1000 mg/day Subjects with body weight 86-105 kg: 1200 mg/day Subjects with body weight > 105 kg: 1400 mg/day
Other Name: Ribasphere
Active Comparator: PEG-Intron® PANEL A
PEG-Intron® 1.5 µg/kg body weight weekly subcutaneous injection
Drug: ribavirin
Ribavirin - oral administration Subjects with body weight < 65 kg: 800 mg/day Subjects with body weight 65-85 kg: 1000 mg/day Subjects with body weight 86-105 kg: 1200 mg/day Subjects with body weight > 105 kg: 1400 mg/day
Other Name: Ribasphere
Active Comparator: PEG-Intron® PANEL B
PEG-Intron® 1.5 µg/kg body weight weekly subcutaneous injection
Drug: ribavirin
Ribavirin - oral administration Subjects with body weight < 65 kg: 800 mg/day Subjects with body weight 65-85 kg: 1000 mg/day Subjects with body weight 86-105 kg: 1200 mg/day Subjects with body weight > 105 kg: 1400 mg/day
Other Name: Ribasphere

Detailed Description:

The aim of the 480 STUDY was to compare efficacy and safety of 480ug Locteron dosed every other week to 1.5 ug/kg PegIntron dosed weekly in treatment-naïve genotype-1 chronic HCV subjects treated with weight-based ribavirin. This 12-week study was comprised of two panels (Panel A and Panel B). The designs of both panels were identical. HCV RNA was measured weekly for three weeks and then every other week. Adverse events including flu-like events and depression were collected during weekly clinic visits for 12 weeks. Flu-like events were also collected daily for 12 weeks by subject self-report using the internet (ePRO). Beck Depression Inventory (BDI) and Short Form-36 scores were measured at baseline and monthly through Week 12.

In Panel A of 480 STUDY, 42 treatment-naïve subjects with chronic genotype-1 HCV in Bulgaria and Romania were randomized and dosed with either Locteron q2weeks or weekly PegIntron, both in combination with weight-based ribavirin (13). In Panel A, 19 subjects received 480ug Locteron and 23 subjects received PegIntron.

In Panel B of 480 STUDY, 32 treatment-naïve subjects with genotype-1 HCV in Israel were randomized and dosed with either Locteron q2weeks or weekly PegIntron, both in combination with weight-based ribavirin (13). In Panel B, 16 subjects received 480ug Locteron and 16 subjects received PegIntron.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects 18 through 69 years of age, inclusive
  • Chronic hepatitis C genotype 1
  • HCV ribonucleic acid (RNA) level > 10,000 IU/mL (by RT-PCR) at screening
  • Creatine clearance ≥ 50 mL/min
  • Neutrophil count > 1500 cells/mm3
  • Platelet count > 90,000/mm3
  • Hemoglobin > 12 g/dL for females and > 13 g/dL for males
  • Female subjects of child-bearing potential agreeing to use dual methods for contraception
  • Male subjects with female sexual partners agreeing to use effective birth control methods
  • Negative serum pregnancy test for women of child-bearing potential
  • Compensated liver disease defined as INR < 1.5, conjugated bilirubin < 1.5 x ULN, serum albumin > 3.0 g/dL
  • Histologic evidence of Chronic Hepatitis C (CHC) (inflammation, fibrosis and/or cirrhosis on a standardized histologic grading system) as shown by biopsy within 2 years of screening or agrees to have a liver biopsy performed prior to randomization.

Exclusion Criteria:

  • Prior antiviral treatment for hepatitis C
  • Co-infection with HIV or hepatitis B virus
  • Subjects with a body mass index (BMI) above 32 kg/m2
  • Current or prior history of clinical hepatic decompensation
  • Evidence of HCC
  • Uncontrolled diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening
  • Known hypersensitivity to interferon alfa or ribavirin
  • Chronic liver disease other than HCV
  • Clinically significant hemoglobinopathy
  • History of moderate, severe or uncontrolled psychiatric disease including depression and prior suicide attempts
  • History of immune-mediated disease
  • Significant renal or neurological disease
  • Severe degree (> GOLD stage III) of chronic pulmonary disease (COPD) or active, severe asthma
  • Subjects with severe cardiac disease
  • History of significant central nervous system (including CNS trauma) or seizure disorders
  • Cancer within the last 5 years, or previous cancer with a high risk of recurrence
  • History of solid organ or bone marrow transplantation
  • Clinical or laboratory evidence of uncontrolled thyroid disease, e.g., by thyroid stimulating hormone (TSH) level > 1.2 x upper limit of normal
  • Clinically significant retinopathy; this needs to have been excluded by an eye exam performed by an ophthalmologist within the last 6 months prior to screening for subjects with hypertension or diabetes mellitus
  • Drug abuse or alcohol consumption within the last 6 months which, in the opinion of the investigator, may affect study participation or outcome. Subjects in a supervised methadone treatment program on a stable regimen for > 6 months may be considered
  • Taken any experimental agent within 12 weeks prior to screening
  • More than 30 days of systemic immunosuppressive medication to include steroids in doses equivalent to or greater than 10 mg prednisone per day within 30 days prior to screening (inhaled corticosteroids are allowed)
  • Nursing mother or male partner of pregnant female.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953589

Locations
Bulgaria
Medical Institute Ministry of Interior
Sofia, Bulgaria, 1606
Tokuda Hospital
Sofia, Bulgaria, 1407
UMHAT "Alexandrovska"
Sofia, Bulgaria, 1431
UMHAT "Queen Giovanna - ISUL" EAD
Sofia, Bulgaria, 1527
UMHAT "St Ivan Rilski"
Sofia, Bulgaria, 1431
UMHAT "St Maria"
Varna, Bulgaria, 9010
Israel
Carmel Medical Center
Haifa, Israel, 34341
Holy Family Hospital Nazareth
Nazareth, Israel, 16100
Rabin Medical Center
Petah-Tiqwa, Israel, 49100
Sourasky Medical Center
Tel Aviv, Israel, 64239
Rebekah Ziv Medical Center Safed
Zefat, Israel, 13100
Romania
Fundeni Clinical Institute
Bucharest, Romania, 022328
Institute of Infectious Diseases
Bucharest, Romania, 021105
"Victor Babes" Clinical Hospital Craiova
Craiova, Romania, 200515
Gastroenterology and Hepatology Institute
Iasi, Romania, 700111
Sponsors and Collaborators
Biolex Therapeutics, Inc.
Investigators
Study Director: Walker A. Long, MD Biolex Therapeutics
  More Information

Publications:
Krastev Z, Kotzev I, Tchernev K, Rigney A, Nikolovska D, Vladimirov B, Caruntu FA, Diaconescu IG, Voiculescu XX, Long, WA. Randomized, open-label, 12-week comparison of controlled-release interferon alpha2b + ribavirin vs. pegylated interferon alpha 2b +ribavirin in treatment-naïve genotype1 hepatitis C: 4 week results from 480STUDY (Panel A). J Hepatology 52:S27 (abstract 58), 2010. (Presented to 45th Annual Meeting of the European Association for the Study of the Liver, April 16, 2010, Vienna, Austria.)

Responsible Party: Biolex Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00953589     History of Changes
Other Study ID Numbers: BLX883-204
Study First Received: August 5, 2009
Last Updated: February 1, 2012
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Romania: National Medicines Agency
Israel: Ministry of Health

Keywords provided by Biolex Therapeutics, Inc.:
treatment naive

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Peginterferon alfa-2b
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014