Efficacy and Safety Evaluation of a Regimen Consisting of Peginterferon Lambda-1a + Ribavirin + Daclatasvir (Lambda + RBV + DCV) in HCV Genotype 1b Treatment naïve Patients or Prior Relapsers to Peginterferon Alfa + Ribavirin (Alfa + RBV) Therapy

Bristol-Myers Squibb444 enrolled

Overview

The purpose of this study is to determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

444

Conditions

Hepatitis C

Interventions

Peginterferon Lambda-1a

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients chronically infected with HCV Genotype-1b * Naïve to prior treatment or documented evidence of relapse after completion of the prescribed duration of treatment (duration may be 24 or 48 weeks, to be determined based upon local guidelines) * HCV RNA viral load ≥100,000 IU/mL at screening * Patients with compensated cirrhosis are permitted Exclusion Criteria: * Infection with Hepatitis C virus (HCV) other than Genotype-1b * Positive Hepatitis B surface antigen (HBsAg) or Human immunodeficiency virus (HIV)-1/HIV-2 antibody test at screening * Evidence of chronic liver disease caused by diseases other than chronic HCV infection * Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening * Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening * Current evidence or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria * Laboratory values: 1. Hemoglobin \<12.0 g/dL (males) or \<11.0 g/dL (females) 2. Platelets \<90,000/mm3 3. Total serum bilirubin ≥2 mg/dL (unless due to Gilbert's disease)

Locations (78)

Va Long Beach Healthcare System

Long Beach, California, United States

Gastrointestinal Specialists Of Georgia Pc

Marietta, Georgia, United States

Weill Cornell Medical College

New York, New York, United States

Premier Medical Group Of The Hudson Valley, Pc

Poughkeepsie, New York, United States

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Outcomes

Primary Outcomes

Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)

Time frame: Post treatment follow-up Week 12

Secondary Outcomes

Proportion of subjects who achieve SVR12 in treatment-naive subjects

Time frame: Post treatment follow-up Week 12

Proportion of subjects with rash related dermatologic events

Time frame: Up to 12 weeks of treatment

Proportion of subjects who develop treatment emergent cytopenic abnormalities

Treatment emergent cytopenic abnormalities \[anemia as defined by Hemoglobin (Hb) \< 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) \< 750/mm3, and or thrombocytopenia as defined by platelets \< 50,000/mm3\]

Time frame: Up to 48 Weeks

Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms

Time frame: Up to 48 Weeks

Proportion of subjects who achieve SVR24 [Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Lower limit of quantitation (LLOQ)] at post-treatment follow-up Week 24

SVR24 = Sustained virologic response at post treatment follow-up Week 24

Time frame: Post treatment follow-up Week 24

Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up

Time frame: Maximum of 72 weeks

Proportion of subjects who achieve SVR12 with a 24-week treatment regimen

Time frame: Post treatment follow-up Week 12

Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)

Time frame: Weeks 4 and 12 of treatment

Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up

Time frame: Maximum of 72 weeks

Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)

Time frame: Maximum of 72 weeks

Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT

Psychiatric symptoms (depression, irritability or insomnia)

Time frame: Maximum of 48 weeks

Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses

For each SNP in each candidate gene, allele and genotype frequencies will be summarized by treatment regimen

Time frame: Post-treatment follow-up Week 12

Resistant variants associated with virologic failure through end of follow-up

Time frame: Maximum of 72 weeks