A Registry for Participants With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection

Hepatitis C Virus Infection Clinical Trial

Official title:

A Registry for Subjects With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02292706
• Other study ID #: GS-US-337-1431
• Secondary ID: 2014-001249-26
• Status: Terminated
• Start date: December 29, 2014
• Est. completion date: December 31, 2021

Study information

• Verified date: December 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The primary objective of this registry study is to assess the durability of sustained virologic response (SVR) and clinical progression or regression of liver disease including the incidence of hepatocellular carcinoma following SVR in participants with cirrhosis after treatment with a sofosbuvir-based regimen for HCV infection.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1609
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Willing and able to provide written informed consent
• Have either previously participated in a Gilead-sponsored HCV study and received a sofosbuvir-containing regimen without interferon OR at pre-selected sites only, have received an all-oral SOF-based regimen outside a clinical study. These individuals must have documentation of the regimen, start and end of treatment dates (month and year), and of having achieved SVR12.
• Have achieved SVR either in a Gilead-sponsored study, as defined in the treatment protocol OR for individuals who enroll after receiving an all-oral SOF-based regimen outside a clinical study, SVR will be defined as HCV RNA < lower limit of quantification (LLOQ) approximately 12 weeks following last dose of treatment.
• Have liver cirrhosis, as defined in the treatment protocol, and have not had a liver transplant after receiving a SOF-containing regimen OR individuals who enroll after receiving an all-oral SOF-based regimen outside a clinical study, will have had cirrhosis confirmed prior to initiation of HCV treatment.

Key Exclusion Criteria:

• Individuals planning to initiate a new course of HCV therapy, including approved products and any investigational agents, during the course of this Registry
• History of clinically-significant illness or any other major medical disorder that may interfere with the follow-up, assessments, or compliance with the protocol Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Communicable Diseases
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Hepatitis C, Chronic
• Infections
• Liver Cirrhosis

Intervention

Drug:
• Sofosbuvir
Exposure of interest for participants who received sofosbuvir in a previous Gilead study for chronic HCV infection.
• Ribavirin

• LDV/SOF
Exposure of interest for participants who received LDV/SOF in a previous Gilead study for chronic HCV infection.
• SOF/VEL
Exposure of interest for participants who received SOF/VEL in a previous Gilead study for chronic HCV infection.
• SOF/VEL/VOX
Exposure of interest for participants who received SOF/VEL/VOX in a previous Gilead study for chronic HCV infection.
• Other SOF-Based Regimen
The other SOF-based regimens may have included the following: BMS-790052 (Daclatasvir) + GS-7977 (SOF) with or without RBV LDV/SOF + GS-9669, GS-7977 (SOF) + with or without RBV + TMC-435 (Simeprevir) LDV/SOF + Vedroprevir (VDV), LDV/SOF + GS-9669 (250 mg and 500 mg) LDV/SOF + VDV + RBV Simeprevir + SOF TMC-435 (Simeprevir) + VEL/SOF

Other:
• Ineligible parent treatment
Participants were enrolled from ineligible parent treatment group.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St Vincents Hospital Sydney	Fitzroy	Victoria
Australia	Fiona Stanley Hospital	Fremantle	Western Australia
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Monash Medical Centre Clayton Campus	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	The Alfred Hospital	Prahran	Victoria
Australia	Kirby Institute	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton
Canada	London Health Sciences Centre - University Campus	London	Ontario
Canada	CRCHUM	Montréal	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Canada	Vancouver Infectious Disease Research and Care Centre	Vancouver	British Columbia
France	Hopital Haut Leveque	Bordeaux
France	CHU Estaing	Clermont Ferrand
France	Hôpital Beaujon	Clichy
France	Hopital Henri Mondor	Creteil Cedex
France	CHU de Grenoble- Hopital Michallon	Grenoble Cedex 9
France	Hôpital Universitaire Dupuytren	Limoges Cedex	Limousin
France	Hopital Saint Joseph	Marseille Cedex 08	Provence Alpes Cote D'Azur
France	CHU Montpellier - Hopital St. Eloi	Montpellier Cedex 05	Languedoc-Rousillon
France	Groupe Hospitalier Archet I Et II	Nice Cedex 3	Provence Alpes Cote D'Azu
France	Hôpital de la Croix Rousse	Paris
France	Hopital de La Pitié-Salpêtrière	Paris	Ile De France
France	Hopital Tenon	Paris
France	Hopital Cochin	Paris, Cedex 14
France	Hôpital Pontchaillou	Rennes	Bretagne
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	Hopital Purpan	Toulouse	Midi-Pyrenees
France	CHU de Nancy-Hopital Brabois Adulte	Vandoeuvre les Nancy
France	Hôpital Paul Brousse	Villejuif
Germany	Klinikum der Johann Wolfgang Goethe Universitat	Frankfurt am Main
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitatsklinikum Koln	Koln
Germany	Technische Universität München	Mücheln
Italy	Azienda Ospedaliera Ospedale Niguarda Cà Granda	Milano
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale Casa Sollievo Della Sofferenza IRCCS	San Giovanni Rotondo
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
New Zealand	Auckland Clinical Studies Ltd	Auckland	North Island
New Zealand	Christchurch Hospital	Christchurch	South Island
New Zealand	Waikato Hospital	Hamilton	North Island
Puerto Rico	Fundacion de Investigation de Diego	San Juan
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Virgen de Valme	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United Kingdom	Gartnavel General Hospital	Glasgow	Scotland
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	Kings College Hospital	London	England
United Kingdom	St Georges University of London	London	England
United Kingdom	North Manchester General Hospital	Manchester	England
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	England
United Kingdom	Queen Alexandra Hospital	Portsmouth
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	INOVA Fairfax Hospital	Annandale	Virginia
United States	The North Texas Clinical Research Institute	Arlington	Texas
United States	Asheville Gastroenterology Associates, PA	Asheville	North Carolina
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Atlanta Medical Center	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Binghamton Gastroenterology Associates, PC	Binghamton	New York
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	BIDMC Liver Center	Boston	Massachusetts
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Digestive Disease Associates, PA	Catonsville	Maryland
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor Endocrine Center	Dallas	Texas
United States	North Texas Research Institute	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	UF Hepatology Research at CTRB	Gainesville	Florida
United States	Gastroenterology Center of the MidSouth, P.C.	Germantown	Tennessee
United States	ID Care, Inc	Hillsborough	New Jersey
United States	St. Luke's Episcopal Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Kansas City Research Institute, LLC	Kansas City	Missouri
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	Scripps Clinic Medical Group	La Jolla	California
United States	V.A. Long Beach Medical Center	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Medical Center	Los Angeles	California
United States	Tarrant County ID Associates	Los Angeles	California
United States	Johns Hopkins Hospital/University	Lutherville	Maryland
United States	North Shore Health Inc.	Manhasset	New York
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Delta Research Partners	Monroe	Louisiana
United States	Intermountain Medical Center	Murray	Utah
United States	Nashville Gastrointestinal Specialists, Inc.	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	New York University Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Bon Secours St. Mary's Hospital of Richmond	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Orlando Immunology Center	Orlando	Florida
United States	The Liver Center	Pasadena	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University Gastroenterology	Providence	Rhode Island
United States	Inland Empire Liver Foundation	Rialto	California
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Davis Medical Center	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	Minnesota Gastroenterology, PA	Saint Paul	Minnesota
United States	The Texas Liver Institute	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	Medical Associates Research Group	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	University of California at San Francisco Medical Center	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Harborview Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Tampa General Hospital	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	South Florida Center of Gastroenterology	Wellington	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  New Zealand,  Puerto Rico,  Spain,  United Kingdom, 

References & Publications (8)

Dunn W, Koestler D, Ni L, Kersey K, Kreter B, Hammond K et al. Cirrhosis regression based on both Enhanced Liver Fibrosis (ELF) and Fibrotest after Direct-acting Hepatitis C therapeutics corresponds to a lower incidence rate of hepatocellular carcinoma below the cost-effective threshold for surveillance [Poster 1289]. The International Liver Congress™ EASL - European Association for the Study of the Liver (EASL); 2021 23-26 June.

Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, Xie Q, Mo S, Sypsa V, Guha IN, Kumada T, Niu J, Dalekos G, Yasuda S, Barnes E, Lian J, Suri V, Idilman R, Barclay ST, Dou X, Berg T, Hayes PC, Flaherty JF, Zhou Y, Zhang Z, Buti M, Hutchinson SJ, Guo Y, Calleja JL, Lin L, Zhao L, Chen Y, Janssen HLA, Zhu C, Shi L, Tang X, Gaggar A, Wei L, Jia J, Irving WL, Johnson PJ, Lampertico P, Hou J. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020 Dec;73(6):1368-1378. doi: 10.1016/j.jhep.2020.07.025. Epub 2020 Jul 21. — View Citation

Jacobson I, Muir AJ, Lawitz EJ, Gane E, Conway B, Ruane PJ, et al. Course of Cirrhosis Regression: Lessons From Patients With HCV Cirrhosis Following Successful Sofosbuvir-Based Treatment [Poster 537]. AASLD: The Liver Meeting® 2019, November 11-15.

Mangia A, Lawitz E, Gane E Conway B, Ruane PJ, Abergel A, et al. Long-Term Follow-up of Patients with Chronic HCV Infection and Compensated or Decompensated Cirrhosis Following Treatment with Sofosbuvir-Based Regimens. The International Liver Congress™ EASL - European Association for the Study of the Liver (EASL); 2018 April 11-15.

Muir AJ, Buti M, Nahass R, Agarwal K, Gane EJ, Strasser SI, et al. Long-term Follow-up of Patients With Chronic HCV Infection and Compensated or Decompensated Cirrhosis Following Treatment With Sofosbuvir-Based Regimens [Poster 880]. AASLD: The Liver Meeting® 2019, November 11-15.

Reddy KR, Bourlière M, Agarwal K, Lawitz E, Osinusi A, Kersey K, et al. Sustained Viral Response Following Treatment With Direct-Acting Antiviral Agents for Chronic Hepatitis C and the Risk of Hepatocellular Carcinoma [Poster FRI-185]. The International Liver Congress™ EASL - European Association for the Study of the Liver (EASL); 2017 19-23 April.

Reddy R, Muir A, Naggie S, Lawitz E, Gane E, Conway B et al. Non-invasive tests of fibrosis and risk of liver-related complications: observations following successful sofosbuvir-based treatment in patients with HCV cirrhosis. J Hepatology 2020;73: S401-S652.

Reddy R, Muir A, Naggie S, Lawitz E, Gane E, Conway B et al. Noninvasive Tests of Fibrosis and Risk of Liver-Related Complications: Lessons From Patients With HCV Cirrhosis Following Successful Sofosbuvir-Based Treatment [Poster 452]. The International Liver Congress™ EASL - European Association for the Study of the Liver (EASL); 2020 27-29 August.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Maintaining Sustained Virologic Response (SVR) at Week 240	SVR at Week 240 was defined as HCV RNA< lower limit of quantification (LLOQ i.e., 15 or 25 international units per milliliter [IU/mL]) or last available HCV RNA< LLOQ with no subsequent follow-up values at Week 240 after enrollment in this registry study. Percentage of participants who maintained SVR status by Week 240 was estimated using a Kaplan-Meier model.	Week 240
Primary	Percentage of Participants With Any Liver-Associated Events	The percentage of participants with any liver-associated events since registry start (enrollment) through Week 240 was estimated using a Kaplan-Meier model.	Enrollment up to 240 weeks
Primary	Percentage of Participants Who Developed Hepatocellular Carcinoma (HCC) Through Week 240	Participants with de novo HCC since registry start were defined as participants who had not been identified with HCC prior to registry start and only had HCC since registry start. The percentage of participants who developed de novo HCC through Week 240 was estimated using a Kaplan-Meier model.	Enrollment up to 240 weeks
Secondary	Number of Participants With Detectable HCV RNA Due to Re-emergence of Pre-existing Virus Through Week 240		Enrollment up to 240 weeks
Secondary	Number of Participants With Detectable HCV Resistance Mutations Through Week 240		Enrollment up to 240 weeks
Secondary	Number of Participants With Detectable HCV RNA Due to Re-infection Through Week 240	Reinfection was defined as HCV RNA > LLOQ on 2 samples collected at least 1 week apart with a different virus than that present prior to treatment baseline in the parent study.	Enrollment up to 240 weeks

External Links

•   Gilead Clinical Trials Website