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

NCT ID: NCT00953589

Last Updated: 2012-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2011-01-31

Brief Summary

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.

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.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Locteron ® PANEL A

PANEL A: Locteron™ 480 µg dosed every 2 weeks in two subcutaneous injections (160 µg and 320 µg)

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: DRUG

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

Locteron ® PANEL B

PANEL B: Locteron™ 480 µg dosed every two weeks in single subcutaneous injections

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: DRUG

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

PEG-Intron® PANEL A

PEG-Intron® 1.5 µg/kg body weight weekly subcutaneous injection

Group Type: ACTIVE_COMPARATOR

ribavirin

Intervention Type: DRUG

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

PEG-Intron® PANEL B

PEG-Intron® 1.5 µg/kg body weight weekly subcutaneous injection

Group Type: ACTIVE_COMPARATOR

ribavirin

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Ribasphere

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biolex Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walker A. Long, MD

Role: STUDY_DIRECTOR

Biolex Therapeutics

Locations

Tokuda Hospital

Sofia, , Bulgaria

UMHAT "Alexandrovska"

Sofia, , Bulgaria

UMHAT "St Ivan Rilski"

Sofia, , Bulgaria

UMHAT "Queen Giovanna - ISUL" EAD

Sofia, , Bulgaria

Medical Institute Ministry of Interior

Sofia, , Bulgaria

UMHAT "St Maria"

Varna, , Bulgaria

Carmel Medical Center

Haifa, , Israel

Holy Family Hospital Nazareth

Nazareth, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Rebekah Ziv Medical Center Safed

Safed, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

Institute of Infectious Diseases

Bucharest, , Romania

Fundeni Clinical Institute

Bucharest, , Romania

"Victor Babes" Clinical Hospital Craiova

Craiova, , Romania

Gastroenterology and Hepatology Institute

Iași, , Romania

Countries

Bulgaria; Israel; Romania

References

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.)

Reference Type: BACKGROUND

Other Identifiers

BLX883-204

Identifier Type: -

Identifier Source: org_study_id