Hepatitis Delta VirusPhase 3D-LIVRNCT03719313

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

A Phase 3 study testing Lonafarnib, Ritonavir and PEG IFN-alfa-2a in people with Hepatitis Delta Virus, run by Eiger BioPharmaceuticals at 116 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis Delta Virus
What is being tested?: Lonafarnib, Ritonavir and PEG IFN-alfa-2a
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 407 participants
Where: 116 sitesin 22 countries
Study dates: 1 Dec 2018to 24 Mar 2023
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

116 sites in 22 countries.

Country

City, postcode or hospital

116 sites in 22 countries

United States18 sites

National Institutes of Health
Bethesda, Maryland, 20814
Rush University Medical Center
Chicago, Illinois, 60612
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8857
Henry Ford Health System
Detroit, Michigan, 48202
UCSF Fresno
Fresno, California, 93701
Baylor St. Luke's Medical Center
Houston, Texas, 77030
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Ruane Clinical Research Group Inc.
Los Angeles, California, 90036
Asia Pacific Liver Center
Los Angeles, California, 90057
University of Miami Schiff Center for Liver Disease
Miami, Florida, 33136
Yale University Medical Center
New Haven, Connecticut, 06510-3206
Mt. Sinai Hospital
New York, New York, 10029
NYU Langone Medical Center
New York, New York, 11016
Central Sooner Research
Norman, Oklahoma, 73071
Stanford University
Palo Alto, California, 94303
University of Rochester Medical Center
Rochester, New York, 14642
University of California Davis Health System
Sacramento, California, 95817
Kaiser Permanente Medical Center Sacramento
Sacramento, California, 95825

Other trials in United States

Italy13 sites

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, 25123
Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
Foggia, 71100
Azienda Ospedaliera Universitaria Policlinico G. Martino
Messina, 98124
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
Milan, 20122
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
Milan, 20162
Universita di Modena e Reggio Emilia. Nuovo Ospedale civil
Modena, 1355
Azienda Ospedaliera Universitaria "Federico II"
Naples, 80131
Azienda Ospedaliero Universitaria di Parma
Parma, 43100
Azienda Ospedaliero Universitaria Pisana
Pisa, 56124
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma, 00133
Istituto Clinico Humanitas
Rozzano, Milano, 20089
IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, 71013
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, 10126

Other trials in Italy

Russia11 sites

Clinic of the Ministry of health of the South Ural state medical UNIVERSITY Russia, 2 infectious diseases Department.
Chelyabinsk, 454052
Krasnodar specialized clinical infectious diseases hospital
Krasnodar, 350000
Modern Medicine Clinic, LLC
Moscow, 121170
H-Clinic, LLC
Moscow, 127083
National medical research center Phthisiopulmonology and infectious diseases of the Ministry of health of the Russian Federation
Moscow, 127473
Healthy Family, LLC
Novosibirsk, 630099
Clinica UZI 4D, LLC
Pyatigorsk, 357502
Medical University "Reaviz"
Samara, 443011
Hepatolog, LLC
Samara, 443063
State Budgetary Educational Institution of Higher Profesional Education "Stavropol State Medical University" of MoH
Stavropol, 355017
Office for treatment of patients with viral hepatitis GBU Sakha (Yakutia) "Yakut Republican clinical hospital"
Yakutsk, 677005

Other trials in Russia

France8 sites

Hôpital Jean Verdier
Bondy, Seine Saint Denis, 93140
Hôpital Beaujon
Clichy, Hauts De Seine, 92110
CHU de Grenoble - Hôpital Nord
La Tronche, Isere, 38043
Centre Hospitalier de la Croix Rousse
Lyon, Rhone, 69004
CHU Nice - Hôpital de l'Archet 2
Nice, Alpes Maritimes, 06200
CHU Bordeaux - Hôpital Haut-Lévêque
Pessac, Gironde, 33604
CHU Strasbourg - Hôpital Hautepierre
Strasbourg, Bas Rhin, 67098
Hôpital Paul Brousse
Villejuif, Val De Marne, 94804

Other trials in France

Germany8 sites

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
Berlin, 10439
Charite - Campus Virchow-Klinikum
Berlin, 13353
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147
Goethe Universität Frankfurt Am Main
Frankfurt am Main, Hesse, 60590
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Israel8 sites

HaEmek Medical Center
Afula, 18101
Soroka University Medical Center
Beersheba, 84001
Rambam Health Care Center
Haifa, 3109601
The Lady Davis Carmel Medical Center
Haifa, 34362
Shaare Zedek Medical Center
Jerusalem, 91031
Hadassah University Hospital - Ein Kerem
Jerusalem, 9112001
Galilee Medical Center
Nahariya, 2210001
Chaim Sheba Medical Center
Ramat Gan, 52363

Other trials in Israel

Ukraine7 sites

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
Medical Center "Harmony of Beauty", LLC
Kyiv, 01135
Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC
Kyiv, 02091
Medical Center "Preventclinic", LLC
Kyiv, 03035
Municipal Enterprise "Poltava Regional Clinical Infectious Hospital of Poltava Regional Council"
Poltava, 36011
University Hospital of Sumy State University
Sumy, 40000
Municipal non-profit enterprise " Vinnytsia city clinical hospital No. 1"
Vinnytsia, 21029

Other trials in Ukraine

Romania6 sites

S.C MedLife S.A
Bucharest, 010719
Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
Bucharest, 010825
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
Bucharest, 021105
Institutul Clinic Fundeni
Bucharest, 022328
Fundatia "Dr. Victor Babes"
Bucharest, 030303
Spitalul Clinic Judetean de Urgenta Cluj Napoca
Cluj-Napoca, 400006

Other trials in Romania

Taiwan6 sites

Changhua Christian Hospital
Changhua, 50004
Chia-Yi Christian Hospital
Chia-Yi City, 600
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 824
Taipei Veterans General Hospital
Taipei, 11217
Chang Gung Memorial Hospital, Linkou
Taoyuan County, 333

Other trials in Taiwan

Belgium5 sites

ZNA Stuivenberg
Antwerp, 2060
C.H.U. Brugmann
Brussels, 1020
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, 1070
Universitair Ziekenhuis Antwerpen
Edegem, 2650
CHU Sart Tilman
Liège, 4000

Other trials in Belgium

Bulgaria4 sites

Acibadem City Clinic Tokuda Hospital Ead
Sofia, 1407
UMHAT "Alexandrovska" EAD
Sofia, 1431
UMHAT "Sv. Ivan Rilski", EAD
Sofia, 1431
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
Stara Zagora, 6000

Other trials in Bulgaria

Canada4 sites

University of Calgary
Calgary, Alberta, T2N 4Z6
McGill University Health Centre/Glen Site / Royal Victoria Hospital
Montreal, Quebec, H4A 3J1
University Health Network
Toronto, Ontario, M5G 2C4
Toronto Liver Centre
Toronto, Ontario, M6H 3M1

Other trials in Canada

Spain3 sites

Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politecnic La Fe
Valencia, 46026

Other trials in Spain

Sweden3 sites

Falu Lasarett
Falun, 79182
Karolinska Universitetssjukhuset Huddinge
Huddinge, 14157
Skånes Universitetssjukhus
Malmö, 205 02

Other trials in Sweden

Turkey (Türkiye)3 sites

Dicle University, Medical Faculty
Diyarbakır, 21280
Koc University Hospital
Istanbul
Ege University Medical Faculty
Izmir, 35100

Other trials in Turkey (Türkiye)

Moldova2 sites

ISMP Spitalul Clinic Republican "Timofei Mosneaga"
Chisinau, 2025
Rtl Sm Srl
Chisinau, MD-2025

Other trials in Moldova

United Kingdom2 sites

Gartnavel General Hospital
Glasgow, Strathclyde, G12 0YN
Royal London Hospital
London, Greater London, E1 1BB

Other trials in United Kingdom

Greece1 site

General Hospital of Athens Laiko
Athens, 11527

Other trials in Greece

Mongolia1 site

The Liver Center
Ulaanbaatar, 14230-0054

Other trials in Mongolia

New Zealand1 site

Auckland City Hospital
Grafton, 1023

Other trials in New Zealand

Pakistan1 site

The Aga Khan University
Karachi, 74800

Other trials in Pakistan

Switzerland1 site

Inselspital Bern, Hepatologie, Bauchzentrum, INO- A, Ms. Kathrin Husi
Bern, 3010

Other trials in Switzerland

About this study

Official title: A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID With and Without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared With PEG IFN-alfa-2a Monotherapy and Placebo Treatment in Patients Chronically Infected With Hepatitis Delta Virus Being Maintained on Anti-HBV Nucleos(t)Ide Therapy (D-LIVR)

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.

Read the 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.

Conditions: Hepatitis Delta Virus
Being tested: Lonafarnib, Ritonavir, PEG IFN-alfa-2a, Placebo Lonafarnib, Placebo Ritonavir
Medical subject headings: Hepatitis D

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LonafarnibDrug
Also called EBP994, Sarasar, LNF
Lonafarnib (LNF) 50 mg BID
RitonavirDrug
Also called Norvir, RTV
Ritonavir (RTV) 100 mg BID
PEG IFN-alfa-2aDrug
Also called Pegasys, pegylated interferon-alfa
PEG IFN alfa-2a 180 mcg QW
Placebo LonafarnibDrug
Placebo
Placebo RitonavirDrug
Placebo

Study groups in NCT03719313
Study group	Role	What they receive
Group 1	Experimental	Lonafarnib 50 mg BID + Ritonavir 100 mg BID Receives: Drug: Lonafarnib; Drug: Ritonavir
Group 2	Experimental	Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW Receives: Drug: Lonafarnib; Drug: Ritonavir; Drug: PEG IFN-alfa-2a
Group 3	Active comparator	placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW Receives: Drug: PEG IFN-alfa-2a; Drug: Placebo Lonafarnib; Drug: Placebo Ritonavir
Group 4	Placebo comparator	placebo Lonafarnib + placebo Ritonavir Receives: Drug: Placebo Lonafarnib; Drug: Placebo Ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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/PEG IFN-alfa-2a 180 mcg QW vs placebo.
Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 201824 Mar 2023

First posted25 Oct 2018
Study start1 Dec 2018
Primary completion6 Oct 2022
Study completion24 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis Delta VirusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 407 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03719313
Sponsor's protocol ID: EIG-LNF-011
Acronym: D-LIVR
Status last verified: Apr 2023
First submitted: 18 Oct 2018
Last updated: 14 Apr 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 37407002