Phase 2B Dose Ranging Study of Locteron Plus Ribavirin to Treat HCV

NCT00863239 | Completed Phase 2 DMC

• 1 other identifier: BLX883-203
• Study Type: interventional
• Target: 116
• Locations: 4 countries
• Sites: 24

Brief Summary

The purpose of the study was to assess in subjects with chronic hepatitis C (treatment-naïve, genotype 1) receiving weight-based doses of ribavirin the virologic response to 3 dose levels of Locteron™, dosed every 2 weeks, in comparison with PEG-Intron™ dosed weekly.

Conditions

Hepatitis C, Chronic

Keywords

treatment naive; genotype 1

Outcome Measures

Primary Outcomes (1)

• EVR: the proportion of subjects in each arm that have at least a 2 log drop in HCV RNA from Baseline

  12 weeks

Secondary Outcomes (1)

• SVR: the proportion of subjects in each arm demonstrating HCV RNA undetectable (< 10 IU/mL) at the end of the follow-up period

  24 weeks

Study Arms (4)

1

EXPERIMENTAL

Locteron™ (controlled-release interferon alpha 2b) 320 µg as biweekly subcutaneous injection

Drug: ribavirin; Drug: Locteron™ (controlled-release interferon alpha 2b)

2

EXPERIMENTAL

Locteron™ (controlled-release interferon alpha 2b) 480 µg as biweekly subcutaneous injection

Drug: ribavirin; Drug: Locteron™ (controlled-release interferon alpha 2b)

3

EXPERIMENTAL

Locteron™ (controlled-release interferon alpha 2b) 640 µg as biweekly subcutaneous injection

Drug: ribavirin; Drug: Locteron™ (controlled-release interferon alpha 2b)

4

ACTIVE COMPARATOR

PEG-Intron™ (12 kDalton pegylated interferon alpha 2b) 1.5 µg/kg body weight weekly subcutaneous injection

Drug: ribavirin; Drug: PEG-Intron™

Interventions

ribavirin DRUG

Co-administered in all arms: oral ribavirin, 200 mg capsules. Subjects with body weight \< 65 kg: 800 mg/day; Subjects with body weight 65-85 kg: 1000 mg/day; Subjects with body weight \> 85 kg: 1200 mg/day.

Also known as: Ribasphere®

1; 2; 3; 4

Locteron™ (controlled-release interferon alpha 2b) DRUG

investigational controlled-release recombinant interferon alpha 2b formulated in 1500/77/23 PolyActive microspheres as a lyophilized powder, reconstituted with carboxymethyl cellulose immediately before subcutaneous injection every other week as part of the treatment of chronic hepatitis C

Also known as: Locteron, PolyActive, BLX-883

1; 2; 3

PEG-Intron™ DRUG

commercially available pegylated interferon alpha 2b injected subcutaneously weekly in a dose of 1.5 ug/kg as part of the treatment of chronic hepatitis C

Also known as: 12 kDalton pegylated interferon

4

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 not limited to HBV, hemochromatosis, auto-immune hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease)
• Clinically significant hemoglobinopathy such as thalassemia major and sickle cell anemia
• 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 (e.g., heart failure, recent \[i.e., within 6 months prior to first dosing\] myocardial infarction, angina, serious arrhythmias, including prolonged QTc \[\> 450 mSec\], uncontrolled hypertension)
• History of significant central nervous system (including CNS trauma) or seizure disorders

Sponsors & Collaborators

• Biolex Therapeutics, Inc.: lead

Study Sites (24)

eStudy site

Chula Vista, California, 91911, United States

Location

eStudy Site

Oceanside, California, 92056, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

University of Louisville Health Care Outpatient Center

Louisville, Kentucky, 40202, United States

Location

Maryland Digestive Disease Research, LLC

Laurel, Maryland, 20707, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

AGA Clinical Research Associates, LLC.

Egg Harbor, New Jersey, 08234, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45219, United States

Location

The Liver Institute at Methodist Dallas

Dallas, Texas, 75203, United States

Location

Alamo Medical Center

San Antonio, Texas, 78215, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

Tokuda Hospital

Sofia, 1407, Bulgaria

Location

UMHAT "Alexandrovska"

Sofia, 1431, Bulgaria

Location

UMHAT "St Ivan Rilski"

Sofia, 1431, Bulgaria

Location

UMHAT "Queen Giovanna - ISUL" EAD

Sofia, 1527, Bulgaria

Location

Medical Institute Ministry of Interior

Sofia, 1606, Bulgaria

Location

Military Medical Academy

Sofia, 1606, Bulgaria

Location

UMHAT "St Marina"

Varna, 9010, Bulgaria

Location

Fundacion de Investigacion de Diego

Santurce, 00909, Puerto Rico

Location

Institute of Infectious Diseases

Bucharest, 021105, Romania

Location

Fundeni Clinical Institute

Bucharest, 022328, Romania

Location

"Victor Babes" Clinical Hospital Craiova

Craiova, 200515, Romania

Location

Related Publications (1)

• 1. Lawitz E, Younossi Z, Mehra P, Rigney A, Krastev Z, Tchernev K, Takov D, Long WA. Early viral response of controlled-release interferon alpha2b and ribavirin vs. pegylated interferon alpha 2b and ribavirin in treatment-naïve genotype1 hepatitis C: 12 week results (SELECT-2 Trial). J Hepatology 52:S114 (abstract 272), 2010. (Presented to 45th Annual Meeting of the European Association for the Study of the Liver, April 15, 2010, Vienna, Austria.) 2. Long WA, Younossi Z, Lawitz E, Kotsev I, Takov D, Tchernev K, Rigney A, Ghalib R, Stoinov S, Balabanska R, Mehra P, Krastev Z. Timing and frequency of depression during HCV-treatment with controlled-release INFa2b (CR2b) vs. pegylated IFNa2b (PEG2b): Results from SELECT-2, a randomized open-label 72-week comparison in 116 treatment-naïve subjects with genotype-1 HCV. J Hepatology 54:S181-182, 2011 (abstract 446). (Presented to the 46th Annual Meeting of the European Association For The Study Of The Liver, Berlin, Germany, March 31, 2011.) 3. Lawitz E, Younossi Z, Mehra P, Rigney A, Krastev Z, Tchernev K, Takov D, Long WA. SVR for controlled-release interferon alpha-2b (CR2b) + ribavirin compared to pegylated intereferon alpha-2b + ribavirin in treatment-naïve genotype-1 (G1) hepatitis C: final results from SELECT-2. J Hepatology 54:S180-181, 2011 (abstract 444). (Presented to the 46th Annual Meeting of the European Association For The Study Of The Liver, Berlin, Germany, March 31, 2011.) 4. Younossi ZM, Lawitz EJ, Krastev Z, Rigney A, Tchernev K, Takov D, Ghalib RH, Long WA. SELECT-2 clinical trial assessing the efficacy and safety of controlled-release interferon alpha-2b (CR2b) +ribavirin (RBV) versus pegylated interferon alpha-2b (PEG2b) +RBV in treatment-naïve genotype-1 (G1) hepatitis C. Gastroenterology 140:S-942, 2011 (abstract su1868). (Presented to Digestive Disease Week 2011, Chicago, Illinois, May 8, 2011.)

  RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin; locteron; polyethylene oxide-polybutylene terephthalate copolymer; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Walker A. Long, MD

  Biolex Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2009
• First Posted: March 17, 2009
• Study Start: March 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2011
• Last Updated: February 2, 2012

Record last verified: 2012-02

Locations

US (13); BU (7); PR (1); RO (3)