Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a

NCT03719313 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: EIG-LNF-011
• Study Type: interventional
• Target: 407
• Locations: 21 countries
• Sites: 115

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.

Conditions

Hepatitis Delta Virus

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (6)

• 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

Study Arms (4)

Group 1

EXPERIMENTAL

Lonafarnib 50 mg BID + Ritonavir 100 mg BID

Drug: Lonafarnib; Drug: Ritonavir

Group 2

EXPERIMENTAL

Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW

Drug: Lonafarnib; Drug: Ritonavir; Drug: PEG IFN-alfa-2a

Group 3

ACTIVE COMPARATOR

placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW

Drug: PEG IFN-alfa-2a; Drug: Placebo Lonafarnib; Drug: Placebo Ritonavir

Group 4

PLACEBO COMPARATOR

placebo Lonafarnib + placebo Ritonavir

Drug: Placebo Lonafarnib; Drug: Placebo Ritonavir

Interventions

Lonafarnib DRUG

Lonafarnib (LNF) 50 mg BID

Also known as: EBP994, Sarasar, LNF

Group 1; Group 2

Ritonavir DRUG

Ritonavir (RTV) 100 mg BID

Also known as: Norvir, RTV

Group 1; Group 2

PEG IFN-alfa-2a DRUG

PEG IFN alfa-2a 180 mcg QW

Also known as: Pegasys, pegylated interferon-alfa

Group 2; Group 3

Placebo Lonafarnib DRUG

Placebo

Group 3; Group 4

Placebo Ritonavir DRUG

Placebo

Group 3; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• Eiger BioPharmaceuticals: lead

Study Sites (116)

UCSF Fresno

Fresno, California, 93701, United States

Location

Ruane Clinical Research Group Inc.

Los Angeles, California, 90036, United States

Location

Asia Pacific Liver Center

Los Angeles, California, 90057, United States

Location

Stanford University

Palo Alto, California, 94303, United States

Location

University of California Davis Health System

Sacramento, California, 95817, United States

Location

Kaiser Permanente Medical Center Sacramento

Sacramento, California, 95825, United States

Location

Yale University Medical Center

New Haven, Connecticut, 06510-3206, United States

Location

University of Miami Schiff Center for Liver Disease

Miami, Florida, 33136, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

National Institutes of Health

Bethesda, Maryland, 20814, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mt. Sinai Hospital

New York, New York, 10029, United States

Location

NYU Langone Medical Center

New York, New York, 11016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Central Sooner Research

Norman, Oklahoma, 73071, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8857, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

C.H.U. Brugmann

Brussels, 1020, Belgium

Location

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

Acibadem City Clinic Tokuda Hospital Ead

Sofia, 1407, Bulgaria

Location

UMHAT "Alexandrovska" EAD

Sofia, 1431, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, 6000, Bulgaria

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

McGill University Health Centre/Glen Site / Royal Victoria Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

CHU Nice - Hôpital de l'Archet 2

Nice, Alpes Maritimes, 06200, France

Location

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, Bas Rhin, 67098, France

Location

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, Gironde, 33604, France

Location

Hôpital Beaujon

Clichy, Hauts De Seine, 92110, France

Location

CHU de Grenoble - Hôpital Nord

La Tronche, Isere, 38043, France

Location

Centre Hospitalier de la Croix Rousse

Lyon, Rhone, 69004, France

Location

Hôpital Jean Verdier

Bondy, Seine Saint Denis, 93140, France

Location

Hôpital Paul Brousse

Villejuif, Val De Marne, 94804, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Goethe Universität Frankfurt Am Main

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, 10439, Germany

Location

Charite - Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

General Hospital of Athens Laiko

Athens, 11527, Greece

Location

HaEmek Medical Center

Afula, 18101, Israel

Location

Soroka University Medical Center

Beersheba, 84001, Israel

Location

Rambam Health Care Center

Haifa, 3109601, Israel

Location

The Lady Davis Carmel Medical Center

Haifa, 34362, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

Location

Galilee Medical Center

Nahariya, 2210001, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52363, Israel

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, 25123, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia

Foggia, 71100, Italy

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98124, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, 20162, Italy

Location

Universita di Modena e Reggio Emilia. Nuovo Ospedale civil

Modena, 1355, Italy

Location

Azienda Ospedaliera Universitaria "Federico II"

Napoli, 80131, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43100, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, 00133, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

ISMP Spitalul Clinic Republican "Timofei Mosneaga"

Chisinau, 2025, Moldova

Location

Rtl Sm Srl

Chisinau, MD-2025, Moldova

Location

The Liver Center

Ulaanbaatar, 14230-0054, Mongolia

Location

Auckland City Hospital

Grafton, 1023, New Zealand

Location

The Aga Khan University

Karachi, 74800, Pakistan

Location

S.C MedLife S.A

Bucharest, 010719, Romania

Location

Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"

Bucharest, 010825, Romania

Location

Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"

Bucharest, 021105, Romania

Location

Institutul Clinic Fundeni

Bucharest, 022328, Romania

Location

Fundatia "Dr. Victor Babes"

Bucharest, 030303, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj Napoca

Cluj-Napoca, 400006, Romania

Location

Clinic of the Ministry of health of the South Ural state medical UNIVERSITY Russia, 2 infectious diseases Department.

Chelyabinsk, 454052, Russia

Location

Krasnodar specialized clinical infectious diseases hospital

Krasnodar, 350000, Russia

Location

Modern Medicine Clinic, LLC

Moscow, 121170, Russia

Location

H-Clinic, LLC

Moscow, 127083, Russia

Location

National medical research center Phthisiopulmonology and infectious diseases of the Ministry of health of the Russian Federation

Moscow, 127473, Russia

Location

Healthy Family, LLC

Novosibirsk, 630099, Russia

Location

Clinica UZI 4D, LLC

Pyatigorsk, 357502, Russia

Location

Medical University "Reaviz"

Samara, 443011, Russia

Location

Hepatolog, LLC

Samara, 443063, Russia

Location

State Budgetary Educational Institution of Higher Profesional Education "Stavropol State Medical University" of MoH

Stavropol, 355017, Russia

Location

Office for treatment of patients with viral hepatitis GBU Sakha (Yakutia) "Yakut Republican clinical hospital"

Yakutsk, 677005, Russia

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Falu Lasarett

Falun, 79182, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Huddinge, 14157, Sweden

Location

Skånes Universitetssjukhus

Malmo, 205 02, Sweden

Location

Inselspital Bern, Hepatologie, Bauchzentrum, INO- A, Ms. Kathrin Husi

Bern, 3010, Switzerland

Location

Changhua Christian Hospital

Changhua, 50004, Taiwan

Location

Chia-Yi Christian Hospital

Chia-Yi City, 600, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 824, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan, 333, Taiwan

Location

Dicle University, Medical Faculty

Diyarbakır, 21280, Turkey (Türkiye)

Location

Koc University Hospital

Istanbul, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Hospital of the state institution "National Institute of Therapy named after L.T. Maloi of the National Academy of Medical Sciences of Ukraine"

Kharkiv, 61039, Ukraine

Location

Medical Center "Harmony of Beauty", LLC

Kyiv, 01135, Ukraine

Location

Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC

Kyiv, 02091, Ukraine

Location

Medical Center "Preventclinic", LLC

Kyiv, 03035, Ukraine

Location

Municipal Enterprise "Poltava Regional Clinical Infectious Hospital of Poltava Regional Council"

Poltava, 36011, Ukraine

Location

University Hospital of Sumy State University

Sumy, 40000, Ukraine

Location

Municipal non-profit enterprise " Vinnytsia city clinical hospital No. 1"

Vinnytsia, 21029, Ukraine

Location

Royal London Hospital

London, Greater London, E1 1BB, United Kingdom

Location

Gartnavel General Hospital

Glasgow, Strathclyde, G12 0YN, United Kingdom

Location

Related Publications (1)

• Asselah T, Rizzetto M. Hepatitis D Virus Infection. N Engl J Med. 2023 Jul 6;389(1):58-70. doi: 10.1056/NEJMra2212151. No abstract available.

  PMID: 37407002 DERIVED

MeSH Terms

Conditions

Hepatitis D

Interventions

lonafarnib; Ritonavir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 25, 2018
• Study Start: December 1, 2018
• Primary Completion: October 6, 2022
• Study Completion: March 24, 2023
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

BE (5); DE (8); CA (4); NZ (1); PA (1); RO (6); RU (11); MO (2); TW (6); IL (8); TU (3); GB (2); IT (13); GR (1); BU (4); FR (8); CH (1); ES (3); US (18); UA (7); SE (3)