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

NCT ID: NCT03719313

Last Updated: 2023-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 407 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2023-03-24

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.

Conditions

Hepatitis Delta Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Lonafarnib 50 mg BID + Ritonavir 100 mg BID

Group Type: EXPERIMENTAL

Lonafarnib

Intervention Type: DRUG

Lonafarnib (LNF) 50 mg BID

Ritonavir

Intervention Type: DRUG

Ritonavir (RTV) 100 mg BID

Group 2

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

Group Type: EXPERIMENTAL

Lonafarnib

Intervention Type: DRUG

Lonafarnib (LNF) 50 mg BID

Ritonavir

Intervention Type: DRUG

Ritonavir (RTV) 100 mg BID

PEG IFN-alfa-2a

Intervention Type: DRUG

PEG IFN alfa-2a 180 mcg QW

Group 3

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

Group Type: ACTIVE_COMPARATOR

PEG IFN-alfa-2a

Intervention Type: DRUG

PEG IFN alfa-2a 180 mcg QW

Placebo Lonafarnib

Intervention Type: DRUG

Placebo

Placebo Ritonavir

Intervention Type: DRUG

Placebo

Group 4

placebo Lonafarnib + placebo Ritonavir

Group Type: PLACEBO_COMPARATOR

Placebo Lonafarnib

Intervention Type: DRUG

Placebo

Placebo Ritonavir

Intervention Type: DRUG

Placebo

Interventions

Lonafarnib

Lonafarnib (LNF) 50 mg BID

Intervention Type: DRUG

Ritonavir

Ritonavir (RTV) 100 mg BID

Intervention Type: DRUG

PEG IFN-alfa-2a

PEG IFN alfa-2a 180 mcg QW

Intervention Type: DRUG

Placebo Lonafarnib

Placebo

Intervention Type: DRUG

Placebo Ritonavir

Placebo

Intervention Type: DRUG

Other Intervention Names

EBP994; Sarasar; LNF; Norvir; RTV; Pegasys; pegylated interferon-alfa

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.

4. Baseline liver biopsy demonstrating evidence of chronic hepatitis.

5. ECGs demonstrating no acute ischemia or clinically significant abnormality.

6. Normal dilated retinal examination.

Exclusion Criteria

General Exclusions

1. Previous use of LNF within 12 months.

2. Current or previous history of decompensated liver disease.

3. Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable HIV RNA and HCV RNA, respectively.

4. Evidence of significant portal hypertension.

5. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.

6. History of hepatocellular carcinoma.

7. Patients with any of the following:

• Current eating disorder
• Evidence of alcohol substance use disorder.
• Drug abuse within the previous 6 months before screening.

8. 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.

9. Other significant medical condition that may require intervention during the study.

10. Any condition that may impact proper absorption.

11. 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.

12. Use of heparin or warfarin.

13. Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV.

14. Receipt of systemic immunosuppressive therapy.

15. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eiger BioPharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCSF Fresno

Fresno, California, United States

Ruane Clinical Research Group Inc.

Los Angeles, California, United States

Asia Pacific Liver Center

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

University of California Davis Health System

Sacramento, California, United States

Kaiser Permanente Medical Center Sacramento

Sacramento, California, United States

Yale University Medical Center

New Haven, Connecticut, United States

University of Miami Schiff Center for Liver Disease

Miami, Florida, 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

NYU Langone Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, 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

ZNA Stuivenberg

Antwerp, , Belgium

C.H.U. Brugmann

Brussels, , Belgium

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

CHU Sart Tilman

Liège, , Belgium

Acibadem City Clinic Tokuda Hospital Ead

Sofia, , Bulgaria

UMHAT "Alexandrovska" EAD

Sofia, , Bulgaria

UMHAT "Sv. Ivan Rilski", EAD

Sofia, , Bulgaria

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, , Bulgaria

University of Calgary

Calgary, Alberta, Canada

University Health Network

Toronto, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

McGill University Health Centre/Glen Site / Royal Victoria Hospital

Montreal, Quebec, Canada

CHU Nice - Hôpital de l'Archet 2

Nice, Alpes Maritimes, France

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, Bas Rhin, France

CHU Bordeaux - Hôpital Haut-Lévêque

Pessac, Gironde, France

Hôpital Beaujon

Clichy, Hauts De Seine, France

CHU de Grenoble - Hôpital Nord

La Tronche, Isere, France

Centre Hospitalier de la Croix Rousse

Lyon, Rhone, France

Hôpital Jean Verdier

Bondy, Seine Saint Denis, France

Hôpital Paul Brousse

Villejuif, Val De Marne, France

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, Germany

Goethe Universität Frankfurt Am Main

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, , Germany

Charite - Campus Virchow-Klinikum

Berlin, , Germany

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

General Hospital of Athens Laiko

Athens, , Greece

HaEmek Medical Center

Afula, , Israel

Soroka University Medical Center

Beersheba, , Israel

Rambam Health Care Center

Haifa, , Israel

The Lady Davis Carmel Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Galilee Medical Center

Nahariya, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Istituto Clinico Humanitas

Rozzano, Milano, Italy

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

Brescia, , Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia

Foggia, , Italy

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, , Italy

Universita di Modena e Reggio Emilia. Nuovo Ospedale civil

Modena, , Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, , Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, , Italy

ISMP Spitalul Clinic Republican "Timofei Mosneaga"

Chisinau, , Moldova

Rtl Sm Srl

Chisinau, , Moldova

The Liver Center

Ulaanbaatar, , Mongolia

Auckland City Hospital

Grafton, , New Zealand

The Aga Khan University

Karachi, , Pakistan

S.C MedLife S.A

Bucharest, , Romania

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

Bucharest, , Romania

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

Bucharest, , Romania

Institutul Clinic Fundeni

Bucharest, , Romania

Fundatia "Dr. Victor Babes"

Bucharest, , 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, , Russia

Krasnodar specialized clinical infectious diseases hospital

Krasnodar, , Russia

Modern Medicine Clinic, LLC

Moscow, , Russia

H-Clinic, LLC

Moscow, , Russia

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

Moscow, , Russia

Healthy Family, LLC

Novosibirsk, , Russia

Clinica UZI 4D, LLC

Pyatigorsk, , Russia

Medical University "Reaviz"

Samara, , Russia

Hepatolog, LLC

Samara, , Russia

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

Stavropol, , Russia

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

Yakutsk, , Russia

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

Karolinska Universitetssjukhuset Huddinge

Huddinge, , Sweden

Skånes Universitetssjukhus

Malmo, , Sweden

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

Bern, , Switzerland

Changhua Christian Hospital

Changhua, , Taiwan

Chia-Yi Christian Hospital

Chia-Yi City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan, , Taiwan

Dicle University, Medical Faculty

Diyarbakır, , Turkey (Türkiye)

Koc University Hospital

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

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

Medical Center "Harmony of Beauty", LLC

Kyiv, , Ukraine

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

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

Vinnytsia, , Ukraine

Royal London Hospital

London, Greater London, United Kingdom

Gartnavel General Hospital

Glasgow, Strathclyde, United Kingdom

Countries

United States; Belgium; Bulgaria; Canada; France; Germany; Greece; Israel; Italy; Moldova; Mongolia; New Zealand; Pakistan; Romania; Russia; Spain; Sweden; Switzerland; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37407002 (View on PubMed)

Other Identifiers

EIG-LNF-011

Identifier Type: -

Identifier Source: org_study_id