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

NCT ID: NCT00863239

Last Updated: 2012-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-11-30

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.

Detailed Description

The aim of SELECT-2 study was to compare the safety and efficacy of Locteron to PegIntron. SELECT-2 was a 72-week Phase 2b, multicenter, international trial of treatment-naïve genotype-1 chronic HCV subjects who were randomized 1:1:1:1 and dosed with one of three doses [640ug (n=29), 480ug (n=29), 320ug (n=28)] of q2week Locteron or weekly doses of 1.5ug/kg PEG2b (n=30). Subjects received these regimens in combination with weight-based ribavirin (800-1400 mg) for up to 48 weeks. Subjects and staff were blinded to Locteron dose for the first 12 weeks. Subjects without early virologic response by 12 weeks, and without viral negativity by 24 weeks, discontinued treatment for lack of efficacy. Adverse events including flu symptoms and depression, Beck Depression Inventory (BDI), Short Form-36, HCV RNA and safety labs were measured at standard intervals at clinic visits through Week 72. In addition, daily subject self-reports of flu symptoms using an electronic subject reporting tool (ePRO) were collected for the first 12 weeks.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

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

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: 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.

Locteron™ (controlled-release interferon alpha 2b)

Intervention Type: 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

2

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

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: 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.

Locteron™ (controlled-release interferon alpha 2b)

Intervention Type: 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

3

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

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: 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.

Locteron™ (controlled-release interferon alpha 2b)

Intervention Type: 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

4

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

Group Type: ACTIVE_COMPARATOR

ribavirin

Intervention Type: 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.

PEG-Intron™

Intervention Type: 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

Interventions

ribavirin

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.

Intervention Type: DRUG

Locteron™ (controlled-release interferon alpha 2b)

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

Intervention Type: DRUG

PEG-Intron™

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

Intervention Type: DRUG

Other Intervention Names

Ribasphere®; Locteron; PolyActive; BLX-883; 12 kDalton pegylated interferon

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.

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 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
• Cancer within the last 5 years, or previous cancer with a high risk of recurrence, including metastatic breast cancer; non-melanoma skin cancer is not an exclusion criterion
• 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

eStudy site

Chula Vista, California, United States

eStudy Site

Oceanside, California, United States

Medical Associates Research Group

San Diego, California, United States

University of Louisville Health Care Outpatient Center

Louisville, Kentucky, United States

Maryland Digestive Disease Research, LLC

Laurel, Maryland, United States

St. Louis University

St Louis, Missouri, United States

AGA Clinical Research Associates, LLC.

Egg Harbor, New Jersey, United States

Montefiore Medical Center

The Bronx, New York, United States

Consultants for Clinical Research

Cincinnati, Ohio, United States

The Liver Institute at Methodist Dallas

Dallas, Texas, United States

Alamo Medical Center

San Antonio, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

McGuire DVAMC

Richmond, Virginia, United States

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

Military Medical Academy

Sofia, , Bulgaria

UMHAT "St Marina"

Varna, , Bulgaria

Fundacion de Investigacion de Diego

Santurce, , Puerto Rico

Institute of Infectious Diseases

Bucharest, , Romania

Fundeni Clinical Institute

Bucharest, , Romania

"Victor Babes" Clinical Hospital Craiova

Craiova, , Romania

Countries

United States; Bulgaria; Puerto Rico; Romania

References

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.)

Reference Type: RESULT

Other Identifiers

BLX883-203

Identifier Type: -

Identifier Source: org_study_id