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

Hepatitis C Clinical Trial

— STRUCTURE  

Official title:

A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01718158
• Other study ID #: AI452-021
• Secondary ID: 2011-005409-65
• Status: Completed
• Phase: Phase 3
• First received: October 29, 2012
• Last updated: September 23, 2015
• Start date: January 2013
• Est. completion date: October 2014

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGermany: Ministry of HealthIsrael: Israeli Health Ministry Pharmaceutical AdministrationIsrael: Ministry of HealthItaly: Ministry of HealthItaly: National Bioethics CommitteeItaly: National Institute of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines AgencyJapan: Pharmaceuticals and Medical Devices AgencyJapan: Ministry of Health, Labor and WelfareKorea: Food and Drug AdministrationPoland: National Institute of MedicinesPoland: Ministry of HealthPoland: Ministry of Science and Higher EducationPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: FSI Scientific Center of Expertise of Medical ApplicationRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationSpain: Spanish Agency of MedicinesTaiwan: Department of HealthTaiwan: National Bureau of Controlled DrugsUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

Biological:
• Peginterferon Lambda-1a

• Peginterferon Alfa-2a

Drug:
• Ribavirin

• Daclatasvir

• Telaprevir

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Prov De Santa Fe	Santa Fe
France	Local Institution	Clichy Cedex
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Villejuif Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Essen
Germany	Local Institution	Hamburg
Germany	Local Institution	Mannheim
Germany	Local Institution	Muenchen
Israel	Local Institution	Haifa
Israel	Local Institution	Tel Aviv
Israel	Local Institution	Tel-Hashomer
Israel	Local Institution	Zafed
Italy	Local Institution	Foggia
Italy	Local Institution	Messina
Italy	Local Institution	Modena
Italy	Local Institution	Pavia
Italy	Local Institution	Pisa
Japan	Local Institution	Gifu
Japan	Local Institution	Higashiibaraki-gun	Ibaraki
Japan	Local Institution	Hiroshima-shi	Hiroshima
Japan	Local Institution	Kawasaki-shi	Kanagawa
Japan	Local Institution	Kitakyushu	Fukuoka
Japan	Local Institution	Kitakyushu-shi	Fukuoka
Japan	Local Institution	Kobe-shi	Hyogo
Japan	Local Institution	Kumamoto
Japan	Local Institution	Kyoto-shi	Kyoto
Japan	Local Institution	Kyoto-shi	Kyoto
Japan	Local Institution	Minato-ku	Tokyo
Japan	Local Institution	Musashino-shi	Tokyo
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Saga
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sumida-ku	Tokyo
Japan	Local Institution	Tanabe-shi	Wakayama
Japan	Local Institution	Yokohama	Kanagawa
Japan	Local Institution	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Poland	Local Institution	Bialystok
Poland	Local Institution	Lodz
Poland	Local Institution	Myslowice
Poland	Local Institution	Wroclaw
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	Stavropol
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Santander
Spain	Local Institution	Zaragoza
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Tainan
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan
United Kingdom	Local Institution	London	Greater London
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Texas Clinical Research Institute, Llc	Arlington	Texas
United States	Medvamc	Houston	Texas
United States	Va Long Beach Healthcare System	Long Beach	California
United States	Gastrointestinal Specialists Of Georgia Pc	Marietta	Georgia
United States	Nashville Medical Research Institute	Nashville	Tennessee
United States	Weill Cornell Medical College	New York	New York
United States	Premier Medical Group Of The Hudson Valley, Pc	Poughkeepsie	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)		Post treatment follow-up Week 12	No
Secondary	Proportion of subjects who achieve SVR12 in treatment-naive subjects		Post treatment follow-up Week 12	No
Secondary	Proportion of subjects with rash related dermatologic events		Up to 12 weeks of treatment	Yes
Secondary	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]	Up to 48 Weeks	Yes
Secondary	Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms		Up to 48 Weeks	No
Secondary	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	Post treatment follow-up Week 24	No
Secondary	Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up		Maximum of 72 weeks	Yes
Secondary	Proportion of subjects who achieve SVR12 with a 24-week treatment regimen		Post treatment follow-up Week 12	No
Secondary	Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)		Weeks 4 and 12 of treatment	No
Secondary	Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up		Maximum of 72 weeks	No
Secondary	Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)		Maximum of 72 weeks	No
Secondary	Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT	Psychiatric symptoms (depression, irritability or insomnia)	Maximum of 48 weeks	No
Secondary	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	Post-treatment follow-up Week 12	No
Secondary	Resistant variants associated with virologic failure through end of follow-up		Maximum of 72 weeks	No

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