A Study of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis

Hepatitis C Virus (HCV) Clinical Trial

— EXPEDITION-8  

Official title:

A Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03089944
• Other study ID #: M16-135
• Secondary ID: 2016-004967-38
• Status: Completed
• Phase: Phase 3
• Start date: April 28, 2017
• Est. completion date: November 8, 2019

Study information

• Verified date: June 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 3b, single arm, open-label, multicenter study in treatment naïve adults with chronic HCV infection and compensated cirrhosis to assess the safety of 8 weeks of treatment with glecaprevir/pibrentasvir and to demonstrate the efficacy of the sustained virologic response 12 weeks post dosing (SVR12) rates of 8 weeks of treatment with glecaprevir/pibrentasvir compared to the historical SVR12 rates of 12 weeks of treatment with glecaprevir/pibrentasvir.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 343
• Est. completion date: November 8, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Screening laboratory result indicating Hepatitis C Virus (HCV) Genotype (GT) 1-6 infection.

• Positive plasma HCV antibody and HCV RNA viral load greater than or equal to 1000 IU/mL at Screening.

• Treatment-naive to any approved or investigational anti-HCV medication.

• Participant must be documented as cirrhotic, with a Child-Pugh score of less than or equal to 6.

Exclusion Criteria:

• Female participant who is pregnant, breastfeeding or is considering becoming pregnant during the study, or for approximately 30 days after the last dose of study drug.

• Any current or historical clinical evidence of decompensated cirrhosis.

• Positive test result at Screening for hepatitis B surface antigen (HBsAg), HBV deoxyribonucleic acid > lower limit of quantification (LLOQ) in subjects with isolated positive antibody to hepatitis B core antigen (anti-HBc) (i.e., negative HBsAg and anti-hepatitis B),or anti human immunodeficiency virus antibody (HIV Ab).

• HCV genotype performed by the central laboratory during screening indicating co-infection with more than one HCV genotype.

• History of suspected or confirmed hepatocellular carcinoma.

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus (HCV)
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Liver Cirrhosis

Intervention

Drug:
• Glecaprevir/Pibrentasvir
Tablet

Locations

Country	Name	City	State
Bulgaria	DCC Fokus-5 - LZIP /ID# 163338	Sofia
Bulgaria	Tokuda Hospital Sofia /ID# 163422	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 163332	Sofia
Bulgaria	Univ Hosp for Active Treat /ID# 163330	Sofia
Canada	University of Calgary /ID# 161185	Calgary	Alberta
Canada	Qe Ii Hsc /Id# 161178	Halifax	Nova Scotia
Canada	The Ottawa Hospital Research /ID# 161179	Ottawa	Ontario
Canada	Toronto General Hospital /ID# 161182	Toronto	Ontario
Canada	Percuro Clinical Research, Ltd /ID# 161184	Victoria	British Columbia
Czechia	Research Site s.r.o /ID# 163020	Plzen
Czechia	Institut Klinicke a Experimeth /ID# 162900	Prague
Czechia	KlinMed s.r.o. /ID# 162893	Prague
France	CHU Amiens Picardie /ID# 163071	Amiens CEDEX 1	Somme
France	CHU Estaing /ID# 163058	Clermont Ferrand
France	Hospital Henri Mondor /ID# 163061	Creteil
France	Hopital de la Croix Rousse /ID# 163073	Lyon
France	CHR Orleans - Hopital de la Source /ID# 163072	Orleans CEDEX 2	Centre-Val De Loire
France	Hôpital Purpan /ID# 163065	TOULOUSE Cedex 9	Haute-Garonne
Greece	General Hospital of Athens Laiko /ID# 162786	Athens	Attiki
Greece	General and Oncology Hospital /ID# 162784	Kifissia
Greece	Reg Gen Univ Hosp Larissa /ID# 162783	Larisa
Greece	Bioclinic Thessaloniki /ID# 162785	Thessaloniki
Hungary	Budai Hepatologiai Centrum /ID# 166511	Budapest
Hungary	Szent Janos Korhaz /ID# 166542	Budapest
Ireland	Beaumont Hospital /ID# 162618	Dublin
Ireland	St Vincent's Hospital /ID# 162617	Dublin 4
Ireland	St. James's Hospital /ID# 162619	Dublin 8	Dublin
Israel	Rambam Health Care Campus /ID# 162023	Haifa
Israel	The Lady Davis Carmel MC /ID# 162017	Haifa
Israel	Sheba Medical Center /ID# 162028	Ramat Gan
Israel	Tel Aviv Sourasky Medical Ctr /ID# 162185	Tel Aviv-Yafo	Tel-Aviv
Italy	A.O.U. Policlinico S.Orsola-Malpighi /ID# 162335	Bologna	Emilia-Romagna
Italy	Polo Universitario Luigi Sacco /ID# 162339	Milan
Italy	ASST Grande Ospedale Metropolitano Niguarda /ID# 162340	Milano	Lombardia
Italy	Universita della Campania Luigi Vanvitelli /ID# 162337	Napoli	Campania
Italy	Istituto Clinico Humanitas /ID# 162336	Rozzano	Milano
Poland	Uniwersytecki Szpital Kliniczn /ID# 162757	Bialystok
Poland	HepID - Diagnostyka I Terapia /ID# 162761	Lublin	Lubelskie
Poland	ID Clinic /ID# 162759	Myslowice
Poland	Centrum Badan Klinicznych, Przychodnia Badan Klinicznych /ID# 162760	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 163785	Lisboa
Portugal	Centro Hosp de Lisboa Central /ID# 163770	Lisbon	Lisboa
Portugal	Centro Hospitalar de Sao Joao /ID# 163766	Porto
Portugal	Centro Hospitalar do Porto EPE /ID# 163765	Porto
Puerto Rico	GHGCPR Research Institute /ID# 162608	Ponce
Puerto Rico	Instituto de Investigacion Cientifica del Sur /ID# 162566	Ponce
Puerto Rico	Klinical Investigations Group /ID# 162565	San Juan
Romania	Institutul Nat. de Boli Infectioase /ID# 163488	Bucuresti
Romania	Institutul Clinic Fundeni /ID# 163479	Sector 2	Bucuresti
Romania	Institutul Clinic Fundeni /ID# 163500	Sector 2	Bucuresti
Romania	Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 163484	Sector 2	Bucuresti
Romania	Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 164449	Sector 2	Bucuresti
Russian Federation	CBSI Central scientific and research institute of epidemiology /ID# 161996	Moscow
Russian Federation	Central Clinical Hospital of R /ID# 163434	Moscow
Russian Federation	LLC Medical Company Hepatolog /ID# 161998	Samara	Samarskaya Oblast
Russian Federation	Stavropol State Medical Univ /ID# 161999	Stavropol
Russian Federation	RSAHI Consulting and Diagnostic Centre /ID# 161995	Tyumen
Spain	Hospital Parc de Salut del Mar /ID# 162198	Barcelona
Spain	Hospital Univ Vall d'Hebron /ID# 162199	Barcelona
Spain	Hospital Universitario Reina S /ID# 162200	Cordoba
Spain	Hospital Donostia /ID# 162197	Donostia
Spain	Hospital Univ Central Asturias /ID# 162195	Oviedo
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 162949	Kaohsiung
Taiwan	China Medical University Hosp /ID# 162950	Taichung City	Taichung
Taiwan	Taipei Veterans General Hosp /ID# 162776	Taipei City
United Kingdom	Basildon University Hospital /ID# 162616	Basildon	Essex
United Kingdom	North Manchester General /ID# 163945	Crumpsall
United Kingdom	Western General Hospital /ID# 162612	Edinburgh
United Kingdom	The Royal Free Hospital /ID# 162614	London	London, City Of
United Kingdom	Queens Medical Centre /ID# 162615	Nottinghamshire
United States	Lehigh Valley Health Network /ID# 162603	Allentown	Pennsylvania
United States	Piedmont Hospital /ID# 162646	Atlanta	Georgia
United States	Felizarta /ID# 162295	Bakersfield	California
United States	Mercy Medical Center /ID# 162291	Baltimore	Maryland
United States	James J. Peters VA Medical Center /ID# 162644	Bronx	New York
United States	Montefiore Medical Center /ID# 162312	Bronx	New York
United States	Northwestern University Feinberg School of Medicine /ID# 162208	Chicago	Illinois
United States	Cleveland Clinic /ID# 162570	Cleveland	Ohio
United States	University Hospitals Cleveland /ID# 162243	Cleveland	Ohio
United States	Texas Digestive Disease Consul /ID# 162648	Dallas	Texas
United States	Unity Point Health /ID# 162247	Des Moines	Iowa
United States	Duke University Medical Center /ID# 162299	Durham	North Carolina
United States	Cumberland Research Assoc /ID# 162212	Fayetteville	North Carolina
United States	University of Texas Health /ID# 162288	Houston	Texas
United States	The University of Iowa Hospita /ID# 162214	Iowa City	Iowa
United States	Southern Therapy and Advanced Research (STAR) LLC /ID# 162241	Jackson	Mississippi
United States	Liver Wellness Center /ID# 162244	Little Rock	Arkansas
United States	VA Long Beach Healthcare System /ID# 162298	Long Beach	California
United States	Usc /Id# 162248	Los Angeles	California
United States	University of Louisville /ID# 162242	Louisville	Kentucky
United States	Univ of Wisconsin Hosp/Clinics /ID# 162645	Madison	Wisconsin
United States	University of Miami /ID# 162210	Miami	Florida
United States	Vanderbilt Univ Med Ctr /ID# 162211	Nashville	Tennessee
United States	Icahn School of Med Mt. Sinai /ID# 162294	New York	New York
United States	Weill Cornell Medical College /ID# 161051	New York	New York
United States	Rnjms /Id# 162213	Newark	New Jersey
United States	CHI Health Alegent Creighton /ID# 162286	Omaha	Nebraska
United States	Univ Nebraska Med Ctr /ID# 162285	Omaha	Nebraska
United States	Mayo Clinic Arizona /ID# 162314	Phoenix	Arizona
United States	St. Josephs Hosp and Med Ctr /ID# 162762	Phoenix	Arizona
United States	Center for Liver Diseases, Oakland /ID# 162568	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth Univ /ID# 162215	Richmond	Virginia
United States	Mayo Clinic - Rochester /ID# 162251	Rochester	Minnesota
United States	Kaiser Permanente - San Diego (Palm Ave) /ID# 162289	San Diego	California
United States	Louisiana Research Ctr. LLC /ID# 162567	Shreveport	Louisiana
United States	Stanford University School of Med /ID# 162209	Stanford	California
United States	Carolinas Center for Liver Dis /ID# 162569	Statesville	North Carolina
United States	Osuchs /Id# 162284	Tulsa	Oklahoma
United States	Cedars-Sinai Medical Center - West Hollywood /ID# 162313	West Hollywood	California
United States	Triple O Research Institute /ID# 162300	West Palm Beach	Florida
Vietnam	National Hospital of Tropical Diseases /ID# 167974	Hanoi
Vietnam	Hoa Hao Medic Co. Ltd. /ID# 168178	Ho Chi Minh
Vietnam	Tropical Diseases Hospital /ID# 168211	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Vietnam,  Bulgaria,  Canada,  Czechia,  France,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (	12 weeks after last dose of study drug
Primary	Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.	12 weeks after last dose of study drug
Secondary	Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.	12 weeks after last dose of study drug
Secondary	Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.	12 weeks after the last dose of study drug
Secondary	Percentage of Participants With On-treatment Virologic Failure in the ITT Population	On-treatment virologic failure was defined as confirmed HCV RNA = 100 IU/mL after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA = LLOQ at end of treatment with at least 6 weeks of treatment.	8 weeks on treatment
Secondary	Percentage of Participants With Post-treatment Relapse	Post-treatment relapse was defined as confirmed HCV RNA = LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned (defined as study drug duration = 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels < LLOQ at the end of treatment excluding participants who had been reinfected.	Up to 12 weeks after the last dose of study drug
Secondary	Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.	12 weeks after the last dose of study drug
Secondary	Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.	12 weeks after the last dose of study drug