Phase 2B Dose Ranging Study of Locteron Plus Ribavirin to Treat HCV (SELECT-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biolex Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00863239
First received: March 16, 2009
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: ribavirin
Drug: Locteron™ (controlled-release interferon alpha 2b)
Drug: PEG-Intron™
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2B, Partially Blinded, Randomized Study in Treatment Naive HCV G1 to Compare the Efficacy, Safety, and Tolerability of Three Doses of Locteron Plus Ribavirin Given Bi-weekly in Comparison With PEG-Intron Plus Ribavirin Given Weekly

Resource links provided by NLM:


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

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

Secondary Outcome Measures:
  • SVR: the proportion of subjects in each arm demonstrating HCV RNA undetectable (< 10 IU/mL) at the end of the follow-up period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 116
Study Start Date: March 2009
Study Completion Date: November 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Locteron™ (controlled-release interferon alpha 2b) 320 µg as biweekly subcutaneous injection
Drug: 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.
Other Name: Ribasphere®
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
Other Names:
  • Locteron
  • PolyActive
  • BLX-883
Experimental: 2
Locteron™ (controlled-release interferon alpha 2b) 480 µg as biweekly subcutaneous injection
Drug: 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.
Other Name: Ribasphere®
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
Other Names:
  • Locteron
  • PolyActive
  • BLX-883
Experimental: 3
Locteron™ (controlled-release interferon alpha 2b) 640 µg as biweekly subcutaneous injection
Drug: 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.
Other Name: Ribasphere®
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
Other Names:
  • Locteron
  • PolyActive
  • BLX-883
Active Comparator: 4
PEG-Intron™ (12 kDalton pegylated interferon alpha 2b) 1.5 µg/kg body weight weekly subcutaneous injection
Drug: 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.
Other Name: Ribasphere®
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
Other Name: 12 kDalton pegylated interferon

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.

  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.

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.
  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: NCT00863239

Locations
United States, California
eStudy site
Chula Vista, California, United States, 91911
eStudy Site
Oceanside, California, United States, 92056
Medical Associates Research Group
San Diego, California, United States, 92123
United States, Kentucky
University of Louisville Health Care Outpatient Center
Louisville, Kentucky, United States, 40202
United States, Maryland
Maryland Digestive Disease Research, LLC
Laurel, Maryland, United States, 20707
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, New Jersey
AGA Clinical Research Associates, LLC.
Egg Harbor Township, New Jersey, United States, 08234
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Ohio
Consultants for Clinical Research
Cincinnati, Ohio, United States, 45219
United States, Texas
The Liver Institute at Methodist Dallas
Dallas, Texas, United States, 75203
Alamo Medical Center
San Antonio, Texas, United States, 78215
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
McGuire DVAMC
Richmond, Virginia, United States, 23249
Bulgaria
Tokuda Hospital
Sofia, Bulgaria, 1407
Military Medical Academy
Sofia, Bulgaria, 1606
UMHAT "St Ivan Rilski"
Sofia, Bulgaria, 1431
Medical Institute Ministry of Interior
Sofia, Bulgaria, 1606
UMHAT "Queen Giovanna - ISUL" EAD
Sofia, Bulgaria, 1527
UMHAT "Alexandrovska"
Sofia, Bulgaria, 1431
UMHAT "St Marina"
Varna, Bulgaria, 9010
Puerto Rico
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, 00909
Romania
Fundeni Clinical Institute
Bucharest, Romania, 022328
Institute of Infectious Diseases
Bucharest, Romania, 021105
"Victor Babes" Clinical Hospital Craiova
Craiova, Romania, 200515
Sponsors and Collaborators
Biolex Therapeutics, Inc.
Investigators
Study Director: Walker A. Long, MD Biolex Therapeutics
  More Information

No publications provided

Responsible Party: Biolex Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00863239     History of Changes
Other Study ID Numbers: BLX883-203
Study First Received: March 16, 2009
Last Updated: February 1, 2012
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Romania: National Medicines Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Biolex Therapeutics, Inc.:
treatment naive
genotype 1

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Ribavirin
Peginterferon alfa-2b
Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014