Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a
- Conditions
- Hepatitis Delta Virus
- Interventions
- Registration Number
- NCT03719313
- Lead Sponsor
- Eiger BioPharmaceuticals
- Brief Summary
Two LNF-containing regimens will be evaluated in the D-LIVR Phase 3 study: (1) LNF/RTV/PEG IFN-alfa-2a and (2) LNF/RTV. Each of these arms will have efficacy endpoints that measure clinical benefit with regard to viral suppression and alanine aminotransferase (ALT) normalization. For each LNF-containing regimen, a composite endpoint of EOT (48 weeks) virologic response and ALT normalization will be used. Virologic response will be defined as a 2 log10 IU/mL reduction from baseline.
- Detailed Description
This partially double-blind, randomized study will employ a matrix (factorial) design to evaluate the efficacy and safety of LNF 50 mg/RTV 100 mg twice per day (BID) with and without PEG IFN-alfa-2a 180 mcg once-weekly (QW) for 48 weeks compared to no treatment (placebo LNF and placebo RTV) in patients chronically infected with hepatitis delta virus (HDV) and receiving anti-HBV (hepatitis B virus) nucleos(t)ide maintenance therapy.
Approximately 400 patients will be randomized with an allocation ratio of 7:5:2:2 All patients will receive/maintain background anti-HBV nucleos(t)ide therapy with entecavir or tenofovir for at least 12 weeks prior to initiating study therapy.
All patients who complete 48 weeks of treatment will have a liver biopsy for histology assessment at EOT and will be followed for an additional 24 weeks off study treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 407
-
Chronic HDV infection for at least 6 months in duration, documented by a positive HDV antibody test and HDV RNA ≥ 500 IU/mL.
Note: All genotypes of HDV permitted.
-
Demonstrable suppression of HBV DNA following at least 12 weeks of anti-HBV nucleos(t)ide treatment with entecavir or tenofovir prior to initiating therapy.
-
Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.
-
Baseline liver biopsy demonstrating evidence of chronic hepatitis.
-
ECGs demonstrating no acute ischemia or clinically significant abnormality.
-
Normal dilated retinal examination.
General Exclusions
-
Previous use of LNF within 12 months.
-
Current or previous history of decompensated liver disease.
-
Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable HIV RNA and HCV RNA, respectively.
-
Evidence of significant portal hypertension.
-
Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.
-
History of hepatocellular carcinoma.
-
Patients with any of the following:
- Current eating disorder
- Evidence of alcohol substance use disorder.
- Drug abuse within the previous 6 months before screening.
-
Prior history or current evidence of any of the following:
- Immunologically mediated disease,
- Retinal disorder or clinically relevant ophthalmic disorder,
- Any malignancy within 5 years before screening,
- Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease,
- Chronic pulmonary disease,
- Pancreatitis or colitis,
- Severe or uncontrolled psychiatric disorder.
-
Other significant medical condition that may require intervention during the study.
-
Any condition that may impact proper absorption.
-
Therapy with an immunomodulatory agent, IFN-α (eg, IFN alfa-2a or IFN-alfa-2b, or pegylated IFN-alfa-2a or alfa 2b), cytotoxic agent, or chronic systemic corticosteroids within 12 months of screening.
-
Use of heparin or warfarin.
-
Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV.
-
Receipt of systemic immunosuppressive therapy.
-
History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2 PEG IFN-alfa-2a Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW Group 3 Placebo Lonafarnib placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW Group 3 Placebo Ritonavir placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW Group 4 Placebo Ritonavir placebo Lonafarnib + placebo Ritonavir Group 4 Placebo Lonafarnib placebo Lonafarnib + placebo Ritonavir Group 3 PEG IFN-alfa-2a placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW Group 1 Lonafarnib Lonafarnib 50 mg BID + Ritonavir 100 mg BID Group 1 Ritonavir Lonafarnib 50 mg BID + Ritonavir 100 mg BID Group 2 Ritonavir Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW Group 2 Lonafarnib Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW
- Primary Outcome Measures
Name Time Method To compare the composite virologic and biochemical response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo. 48 weeks To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo. 48 weeks
- Secondary Outcome Measures
Name Time Method To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo. 48 weeks To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo. 48 weeks To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo. 48 weeks To evaluate the health-related quality of life (HRQL) over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo. 48 weeks To evaluate the HRQL over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo. 48 weeks To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo. 48 weeks
Trial Locations
- Locations (116)
University of Miami Schiff Center for Liver Disease
🇺🇸Miami, Florida, United States
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
🇮🇹Roma, Italy
Yale University Medical Center
🇺🇸New Haven, Connecticut, United States
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Bruxelles, Belgium
C.H.U. Brugmann
🇧🇪Bruxelles, Belgium
NYU Langone Medical Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Rtl Sm Srl
🇲🇩Chisinau, Moldova, Republic of
The Aga Khan University
🇵🇰Karachi, Pakistan
Fundatia "Dr. Victor Babes"
🇷🇴Bucuresti, Romania
State Budgetary Educational Institution of Higher Profesional Education "Stavropol State Medical University" of MoH
🇷🇺Stavropol, Russian Federation
Soroka University Medical Center
🇮🇱Beer-Sheva, Israel
Rambam Health Care Center
🇮🇱Haifa, Israel
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Hepatolog, LLC
🇷🇺Samara, Russian Federation
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
🇧🇬Stara Zagora, Bulgaria
McGill University Health Centre/Glen Site / Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
HaEmek Medical Center
🇮🇱Afula, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
ISMP Spitalul Clinic Republican "Timofei Mosneaga"
🇲🇩Chisinau, Moldova, Republic of
Healthy Family, LLC
🇷🇺Novosibirsk, Russian Federation
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Modern Medicine Clinic, LLC
🇷🇺Moscow, Russian Federation
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
🇷🇴Bucuresti, Romania
Institutul Clinic Fundeni
🇷🇴Bucuresti, Romania
Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
🇷🇴Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta Cluj Napoca
🇷🇴Cluj-Napoca, Romania
Clinic of the Ministry of health of the South Ural state medical UNIVERSITY Russia, 2 infectious diseases Department.
🇷🇺Chelyabinsk, Russian Federation
Krasnodar specialized clinical infectious diseases hospital
🇷🇺Krasnodar, Russian Federation
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Office for treatment of patients with viral hepatitis GBU Sakha (Yakutia) "Yakut Republican clinical hospital"
🇷🇺Yakutsk, Russian Federation
Inselspital Bern, Hepatologie, Bauchzentrum, INO- A, Ms. Kathrin Husi
🇨🇭Bern, Switzerland
Municipal non-profit enterprise " Vinnytsia city clinical hospital No. 1"
🇺🇦Vinnytsia, Ukraine
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC
🇺🇦Kyiv, Ukraine
Medical Center "Preventclinic", LLC
🇺🇦Kyiv, Ukraine
Municipal Enterprise "Poltava Regional Clinical Infectious Hospital of Poltava Regional Council"
🇺🇦Poltava, Ukraine
University Hospital of Sumy State University
🇺🇦Sumy, Ukraine
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
UCSF Fresno
🇺🇸Fresno, California, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
Asia Pacific Liver Center
🇺🇸Los Angeles, California, United States
Ruane Clinical Research Group Inc.
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Kaiser Permanente Medical Center Sacramento
🇺🇸Sacramento, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
National Institutes of Health
🇺🇸Bethesda, Maryland, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mt. Sinai Hospital
🇺🇸New York, New York, United States
Central Sooner Research
🇺🇸Norman, Oklahoma, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Acibadem City Clinic Tokuda Hospital Ead
🇧🇬Sofia, Bulgaria
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
UMHAT "Alexandrovska" EAD
🇧🇬Sofia, Bulgaria
CHU Sart Tilman
🇧🇪Liège, Belgium
University Health Network
🇨🇦Toronto, Ontario, Canada
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
CHU Nice - Hôpital de l'Archet 2
🇫🇷Nice Cedex 3, Alpes Maritimes, France
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg Cedex, Bas Rhin, France
CHU Bordeaux - Hôpital Haut-Lévêque
🇫🇷Pessac, Gironde, France
CHU de Grenoble - Hôpital Nord
🇫🇷La Tronche, Isere, France
Hôpital Paul Brousse
🇫🇷Villejuif, Val De Marne, France
Centre Hospitalier de la Croix Rousse
🇫🇷Lyon, Rhone, France
Hôpital Beaujon
🇫🇷Clichy cedex, Hauts De Seine, France
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Baden Wuerttemberg, Germany
Hôpital Jean Verdier
🇫🇷Bondy, Seine Saint Denis, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Baden Wuerttemberg, Germany
Goethe Universität Frankfurt Am Main
🇩🇪Frankfurt, Hessen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
🇩🇪Berlin, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein Westfalen, Germany
General Hospital of Athens Laiko
🇬🇷Athens, Greece
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
🇮🇹Foggia, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
🇮🇹Milano, Italy
Universita di Modena e Reggio Emilia. Nuovo Ospedale civil
🇮🇹Modena, Italy
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹Messina, Italy
Azienda Ospedaliera Universitaria "Federico II"
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Auckland City Hospital
🇳🇿Grafton, New Zealand
The Liver Center
🇲🇳Ulaanbaatar, Mongolia
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
S.C MedLife S.A
🇷🇴Bucuresti, Romania
H-Clinic, LLC
🇷🇺Moscow, Russian Federation
Clinica UZI 4D, LLC
🇷🇺Pyatigorsk, Russian Federation
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Falu Lasarett
🇸🇪Falun, Sweden
Medical University "Reaviz"
🇷🇺Samara, Russian Federation
Karolinska Universitetssjukhuset Huddinge
🇸🇪Huddinge, Sweden
Skånes Universitetssjukhus
🇸🇪Malmö, Sweden
Chia-Yi Christian Hospital
🇨🇳Chia-Yi City, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan County, Taiwan
Dicle University, Medical Faculty
🇹🇷Diyarbakir, Turkey
Hospital of the state institution "National Institute of Therapy named after L.T. Maloi of the National Academy of Medical Sciences of Ukraine"
🇺🇦Kharkiv, Ukraine
Koc University Hospital
🇹🇷Istanbul, Turkey
Medical Center "Harmony of Beauty", LLC
🇺🇦Kyiv, Ukraine
Royal London Hospital
🇬🇧London, Greater London, United Kingdom
Gartnavel General Hospital
🇬🇧Glasgow, Strathclyde, United Kingdom
University of Calgary
🇨🇦Calgary, Alberta, Canada
National medical research center Phthisiopulmonology and infectious diseases of the Ministry of health of the Russian Federation
🇷🇺Moscow, Russian Federation