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

Hepatitis C, Chronic Clinical Trial

— SELECT-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00863239
• Other study ID #: BLX883-203
• Status: Completed
• Phase: Phase 2
• First received: March 16, 2009
• Last updated: February 1, 2012
• Start date: March 2009
• Est. completion date: November 2011

Study information

• Verified date: February 2012
• Source: Biolex Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBulgaria: Bulgarian Drug AgencyFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesRomania: National Medicines AgencySerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: November 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C, Chronic

Intervention

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.
• 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
• 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

Locations

Country	Name	City	State
Bulgaria	Medical Institute Ministry of Interior	Sofia
Bulgaria	Military Medical Academy	Sofia
Bulgaria	Tokuda Hospital	Sofia
Bulgaria	UMHAT "Alexandrovska"	Sofia
Bulgaria	UMHAT "Queen Giovanna - ISUL" EAD	Sofia
Bulgaria	UMHAT "St Ivan Rilski"	Sofia
Bulgaria	UMHAT "St Marina"	Varna
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
Romania	Fundeni Clinical Institute	Bucharest
Romania	Institute of Infectious Diseases	Bucharest
Romania	"Victor Babes" Clinical Hospital Craiova	Craiova
United States	Montefiore Medical Center	Bronx	New York
United States	eStudy site	Chula Vista	California
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	The Liver Institute at Methodist Dallas	Dallas	Texas
United States	AGA Clinical Research Associates, LLC.	Egg Harbor Township	New Jersey
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Maryland Digestive Disease Research, LLC	Laurel	Maryland
United States	University of Louisville Health Care Outpatient Center	Louisville	Kentucky
United States	eStudy Site	Oceanside	California
United States	McGuire DVAMC	Richmond	Virginia
United States	Alamo Medical Center	San Antonio	Texas
United States	Medical Associates Research Group	San Diego	California
United States	St. Louis University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Biolex Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Puerto Rico,  Romania, 

References & 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 w

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EVR: the proportion of subjects in each arm that have at least a 2 log drop in HCV RNA from Baseline		12 weeks	No
Secondary	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	No