Sofosbuvir and Ribavirin in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

Hepatitis C Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GS-7977+Ribavirin for 12 Weeks in Treatment Naive and Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01682720
• Other study ID #: GS-US-334-0133
• Secondary ID: 2012-001942-16
• Status: Completed
• Phase: Phase 3
• First received: September 5, 2012
• Last updated: October 8, 2014
• Start date: September 2012
• Est. completion date: January 2014

Study information

• Verified date: October 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesAustria: Federal Office for Safety in Health CarePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSweden: Medical Products AgencyItaly: Ethics CommitteeFrance: Agence Nationale de Sécurité du Médicament et des produits de santéUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: Agencia Española de Medicamentos y Productos SanitariosEstonia: The State Agency of MedicineNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, and antiviral efficacy of GS-7977 with ribavirin (RBV) in participants with genotype 2 or 3 hepatitis C virus (HCV) infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 421
• Est. completion date: January 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 with chronic genotype 2 or 3 HCV infection

• HCV RNA > 10,000 IU/mL at screening

• Subjects must be treatment naive or treatment experienced

• Presence or absence of cirrhosis; a liver biopsy may be required

• Healthy according to medical history and physical examination with the exception of HCV diagnosis

• Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication

Exclusion Criteria:

• Prior use of any other inhibitor of the HCV NS5B Polymerase

• History of any other clinically significant chronic liver disease

• Evidence of or history of decompensated liver disease

• HIV or chronic hepatitis B virus (HBV) infection

• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)

• Chronic use of immunosuppressive agents or immunomodulatory agents

• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator

Study Design

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

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
• RBV
Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and = 75 kg = 1200 mg)
• Placebo to match SOF
Placebo to match SOF administered orally once daily
• Placebo to match RBV
Placebo to match RBV administered orally in a divided daily dose

Locations

Country	Name	City	State
Austria	Medizinische Universitat Graz	Graz
Austria	Medizinische Universitat Wien	Wien
Austria	Wilhelminenspital	Wien
Estonia	West Tallinn Central Hospital	Tallin
Estonia	Tartu University Hospital	Tartu
France	CHRU de Lille, Hopital Claude Huriez	CHRU Lille
France	CHU Estaing	Clermont Ferrand
France	Hopital Beaujon	Clichy Cedex
France	Hopital Henri Mondor	Creteil Cedex
France	Département Hépatogastroentérologie - CHU de Grenoble	Grenoble
France	Hopital Saint Joseph	Marseille, Cedex 8
France	Hopital Saint Eloi	Montpellier
France	Hopital de l Archet 2	Nice
France	Hopital Pitie Salpetriere	Paris
France	Hopital Saint Antoine	Paris
France	Hopitaux Universitaires	Paris, Cedex 14
France	Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN	Pessac
France	CHU Pontchaillou - Hématologie Clinique	Rennes Cedex 9
France	Centre Hospitalier Universitaire de Strasbourg	Strasbourg
France	CHU de Nancy, Hôpital de Brabois	Vandoeuvre les Nancy
Germany	Leber- and Studienzentrum am Checkpoint	Berlin
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Heinrich Heine Unversitat	Dusseldorf
Germany	JWG-Universität Frankfurt	Frankfurt am Main
Germany	Praxiszentrum	Freiburg	Baden Wuerttemberg
Germany	Asklepios Klinik Sankt Georg H	Hamburg
Germany	Universitatsklinikum	Hamburg
Germany	Medizinische Hochschule Hannov	Hannover
Germany	Medizinische Klinik IV, Dep. o	Heidelberg
Germany	Gastroenterologische Gemeinsch	Herne
Germany	Leberstudienzentrum Kiel	Kiel
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Klinikum der Universität Münch	Munchen
Germany	Centrum fuer interdisziplinaere Medizin Muenster GmbH	Münster
Italy	Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi	Bologna
Italy	Ospedale S. Annunziata	Florence
Italy	Ente Ospedaliero Ospedali Galliera	Genova
Italy	Azienda Ospedaliera Ospedale Niguarda Cà Granda	Milano
Italy	Fondazione IRCCS CA Granada - Ospedale Maggiore Policlinico	Milano
Italy	University of Padova	Padova
Italy	University of Palermo	Palermo
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Fondazione PTV - Policlinico Tor Vergata	Roma
Italy	INMI "Lazzaro Spallanzani" I.R.C.C.S.	Roma
Italy	Ospedale Casa Sollievo	San Giovanni Rotondo	Foggia
Italy	Azienda Ospedaliera Universitaria San Giovanni Battista di Torino	Torino
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	UMC St. Radboud - Gastroenterology	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Poland	Wojewodzki Szpital Specjalistyczny im Dluskeigo	Bialystok
Poland	Wojewodzki Specjalistyczny Szpital im. W. Bieganskiego	Lodz
Poland	SP ZOZ Wojewodzki Szpital Zakazny w Warszawie	Warszawa
Poland	NZOZ Centrum Badan Klinicznych	Wroclaw
Spain	Hospital Casa de la Maternidad	Barcelona
Spain	Hospital Universitari Vall d'H	Barcelona
Spain	Hospital Carlos III	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Puerta de Hierro Maja	Majadahonda
Spain	Complejo Hospitalario de Especialidades Virgen de la Victoria	Malaga
Spain	Hospital Universitario Marques	Santander
Spain	Valme Hospital	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Skånes Universitetssjukhus, Lund	Lund
Sweden	Skanes Universitetssjukhus	Malmo
Sweden	Karolinska Instituet	Stockholm
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	North Manchester General Hospital	Crumpsall	Manchester
United Kingdom	King's College Hospital	Denmark Hill	London
United Kingdom	University of Birmingham	Edgbaston	Birmingham
United Kingdom	Chelsea & Westminster Hospital	London
United Kingdom	Queen Marys University of London	London
United Kingdom	Royal Free Hospital and University College London Hospital	London
United Kingdom	Nottingham University Hospitals-NHS	Nottingham
United Kingdom	The Liver Unit	Paddington	London
United Kingdom	Southampton University Hospital NHS Trust	Southhampton	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Austria,  Estonia,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hézode C, Esteban R; VALENCE Investigators. Sofosbuvir and ribavirin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks following the last dose of study drug. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.	Posttreatment Week 12	No
Primary	Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	The percentage of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was analyzed.	Up to 24 weeks	No
Secondary	Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR24 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.	Posttreatment Weeks 4 and 24	No
Secondary	Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse	Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment.; Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.; Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.	Up to Posttreatment Week 24	No