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

Sponsor
Eiger BioPharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03719313
Collaborator
(none)
400
Enrollment
118
Locations
4
Arms
52
Anticipated Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Dec 1, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Apr 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1

Lonafarnib 50 mg BID + Ritonavir 100 mg BID

Drug: Lonafarnib
Lonafarnib (LNF) 50 mg BID
Other Names:
  • EBP994
  • Sarasar
  • LNF

    • Drug: Ritonavir
    Ritonavir (RTV) 100 mg BID
    Other Names:
  • Norvir
  • RTV

    		•
    Experimental: Group 2

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

    Drug: Lonafarnib
    Lonafarnib (LNF) 50 mg BID
    Other Names:
  • EBP994
  • Sarasar
  • LNF

    • Drug: Ritonavir
    Ritonavir (RTV) 100 mg BID
    Other Names:
  • Norvir
  • RTV

    • Drug: PEG IFN-alfa-2a
    PEG IFN alfa-2a 180 mcg QW
    Other Names:
  • Pegasys
  • pegylated interferon-alfa

    		•
    Active Comparator: Group 3

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

    Drug: PEG IFN-alfa-2a
    PEG IFN alfa-2a 180 mcg QW
    Other Names:
  • Pegasys
  • pegylated interferon-alfa

    • Drug: Placebo Lonafarnib
    Placebo

    Drug: Placebo Ritonavir
    Placebo
    Placebo Comparator: Group 4

    placebo Lonafarnib + placebo Ritonavir

    Drug: Placebo Lonafarnib
    Placebo

    Drug: Placebo Ritonavir
    Placebo

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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 Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. 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]

    5. 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]

    6. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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.

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

    3. Baseline liver biopsy demonstrating evidence of chronic hepatitis.

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

    5. 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.

    1. 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.

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

    2. Any condition that may impact proper absorption.

    3. 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.

    4. Use of heparin or warfarin.

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

    6. Receipt of systemic immunosuppressive therapy.

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSF Fresno Fresno California United States 93701
    2 Ruane Clinical Research Group Inc. Los Angeles California United States 90036
    3 Asia Pacific Liver Center Los Angeles California United States 90057
    4 Stanford University Palo Alto California United States 94303
    5 University of California Davis Health System Sacramento California United States 95817
    6 Kaiser Permanente Medical Center Sacramento Sacramento California United States 95825
    7 Yale University Medical Center New Haven Connecticut United States 06510-3206
    8 University of Miami Schiff Center for Liver Disease Miami Florida United States 33136
    9 Rush University Medical Center Chicago Illinois United States 60612
    10 University of Iowa Hospitals & Clinics Iowa City Iowa United States 52242
    11 National Institutes of Health Bethesda Maryland United States 20814
    12 Henry Ford Health System Detroit Michigan United States 48202
    13 Mt. Sinai Hospital New York New York United States 10029
    14 NYU Langone Medical Center New York New York United States 11016
    15 University of Rochester Medical Center Rochester New York United States 14642
    16 Central Sooner Research Norman Oklahoma United States 73071
    17 University of Texas Southwestern Medical Center Dallas Texas United States 75390-8857
    18 Baylor St. Luke's Medical Center Houston Texas United States 77030
    19 ZNA Stuivenberg Antwerpen Belgium 2060
    20 C.H.U. Brugmann Bruxelles Belgium 1020
    21 Cliniques Universitaires de Bruxelles Hopital Erasme Bruxelles Belgium 1070
    22 Universitair Ziekenhuis Antwerpen Edegem Belgium 2650
    23 CHU Sart Tilman Liège Belgium 4000
    24 Acibadem City Clinic Tokuda Hospital Ead Sofia Bulgaria 1407
    25 UMHAT "Alexandrovska" EAD Sofia Bulgaria 1431
    26 UMHAT "Sv. Ivan Rilski", EAD Sofia Bulgaria 1431
    27 Medical Center "Nov Rehabilitatsionen Tsentar", EOOD Stara Zagora Bulgaria 6000
    28 University of Calgary Calgary Alberta Canada T2N 4Z6
    29 University Health Network Toronto Ontario Canada M5G 2C4
    30 Toronto Liver Centre Toronto Ontario Canada M6H 3M1
    31 McGill University Health Centre/Glen Site / Royal Victoria Hospital Montreal Quebec Canada H4A 3J1
    32 CHU Nice - Hôpital de l'Archet 2 Nice Cedex 3 Alpes Maritimes France 06200
    33 CHU Strasbourg - Hôpital Hautepierre Strasbourg Cedex Bas Rhin France 67098
    34 CHU Bordeaux - Hôpital Haut-Lévêque Pessac Gironde France 33604
    35 Hôpital Beaujon Clichy cedex Hauts De Seine France 92110
    36 CHU de Grenoble - Hôpital Nord La Tronche Isere France 38043
    37 Centre Hospitalier de la Croix Rousse Lyon Rhone France 69004
    38 Hôpital Jean Verdier Bondy Seine Saint Denis France 93140
    39 Hôpital Paul Brousse Villejuif Val De Marne France 94804
    40 Universitaetsklinikum Freiburg Freiburg Baden Wuerttemberg Germany 79106
    41 Universitaetsklinikum Tuebingen Tuebingen Baden Wuerttemberg Germany 72076
    42 Goethe Universität Frankfurt Am Main Frankfurt Hessen Germany 60590
    43 Medizinische Hochschule Hannover Hannover Niedersachsen Germany 30625
    44 Universitaetsklinikum Essen Essen Nordrhein Westfalen Germany 45147
    45 Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH Berlin Germany 10439
    46 Charite - Campus Virchow-Klinikum Berlin Germany 13353
    47 Universitaetsklinikum Hamburg-Eppendorf Hamburg Germany 20246
    48 General Hospital of Athens Laiko Athens Greece 11527
    49 HaEmek Medical Center Afula Israel 18101
    50 Soroka University Medical Center Beer-Sheva Israel 84001
    51 Rambam Health Care Center Haifa Israel 3109601
    52 The Lady Davis Carmel Medical Center Haifa Israel 34362
    53 Shaare Zedek Medical Center Jerusalem Israel 91031
    54 Hadassah University Hospital - Ein Kerem Jerusalem Israel 9112001
    55 Galilee Medical Center Nahariya Israel 2210001
    56 Chaim Sheba Medical Center Ramat Gan Israel 52363
    57 IRCCS Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo Foggia Italy 71013
    58 Istituto Clinico Humanitas Rozzano Milano Italy 20089
    59 Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) Brescia Italy 25123
    60 Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia Foggia Italy 71100
    61 Azienda Ospedaliera Universitaria Policlinico G. Martino Messina Italy 98124
    62 Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico Milano Italy 20122
    63 Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) Milano Italy 20162
    64 Universita di Modena e Reggio Emilia. Nuovo Ospedale civil Modena Italy 1355
    65 Azienda Ospedaliera Universitaria "Federico II" Napoli Italy 80131
    66 Azienda Ospedaliero Universitaria di Parma Parma Italy 43100
    67 Azienda Ospedaliero Universitaria Pisana Pisa Italy 56124
    68 Azienda Ospedaliera Universitaria Policlinico Tor Vergata Roma Italy 00133
    69 Azienda Ospedaliera Città della Salute e della Scienza di Torino Torino Italy 10126
    70 ISMP Spitalul Clinic Republican "Timofei Mosneaga" Chisinau Moldova, Republic of 2025
    71 Rtl Sm Srl Chisinau Moldova, Republic of MD-2025
    72 The Liver Center Ulaanbaatar Mongolia 14230-0054
    73 Auckland City Hospital Grafton New Zealand 1023
    74 The Aga Khan University Karachi Pakistan 74800
    75 S.C MedLife S.A Bucuresti Romania 010719
    76 Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila" Bucuresti Romania 010825
    77 Institutul National de Boli Infectioase "Prof. Dr. Matei Bals" Bucuresti Romania 021105
    78 Institutul National de Boli Infectioase "Prof. Dr. Matei Bals" Bucuresti Romania 021105
    79 Institutul Clinic Fundeni Bucuresti Romania 022328
    80 Institutul Clinic Fundeni Bucuresti Romania 022328
    81 Fundatia "Dr. Victor Babes" Bucuresti Romania 030303
    82 Spitalul Clinic Judetean de Urgenta Cluj Napoca Cluj-Napoca Romania 400006
    83 Clinic of the Ministry of health of the South Ural state medical UNIVERSITY Russia, 2 infectious diseases Department. Chelyabinsk Russian Federation 454052
    84 Krasnodar specialized clinical infectious diseases hospital Krasnodar Russian Federation 350000
    85 Modern Medicine Clinic, LLC Moscow Russian Federation 121170
    86 H-Clinic, LLC Moscow Russian Federation 127083
    87 National medical research center Phthisiopulmonology and infectious diseases of the Ministry of health of the Russian Federation Moscow Russian Federation 127473
    88 Healthy Family, LLC Novosibirsk Russian Federation 630099
    89 Clinica UZI 4D, LLC Pyatigorsk Russian Federation 357502
    90 Medical University "Reaviz" Samara Russian Federation 443011
    91 Hepatolog, LLC Samara Russian Federation 443063
    92 State Budgetary Educational Institution of Higher Profesional Education "Stavropol State Medical University" of MoH Stavropol Russian Federation 355017
    93 Office for treatment of patients with viral hepatitis GBU Sakha (Yakutia) "Yakut Republican clinical hospital" Yakutsk Russian Federation 677005
    94 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    95 Hospital Universitario La Paz Madrid Spain 28046
    96 Hospital Universitari i Politecnic La Fe Valencia Spain 46026
    97 Falu Lasarett Falun Sweden 79182
    98 Karolinska Universitetssjukhuset Huddinge Huddinge Sweden 14157
    99 Skånes Universitetssjukhus Malmö Sweden 205 02
    100 Inselspital Bern, Hepatologie, Bauchzentrum, INO- A, Ms. Kathrin Husi Bern Switzerland 3010
    101 Changhua Christian Hospital Changhua Taiwan 50004
    102 Chia-Yi Christian Hospital Chia-Yi City Taiwan 600
    103 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 807
    104 Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan 824
    105 Taipei Veterans General Hospital Taipei Taiwan 11217
    106 Chang Gung Memorial Hospital, Linkou Taoyuan County Taiwan 333
    107 Dicle University, Medical Faculty Diyarbakir Turkey 21280
    108 Koc University Hospital Istanbul Turkey
    109 Ege University Medical Faculty Izmir Turkey 35100
    110 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 61039
    111 Medical Center "Harmony of Beauty", LLC Kyiv Ukraine 01135
    112 Medical Center 'Ok!Clinic+' of International Institute of Clinical Research LLC Kyiv Ukraine 02091
    113 Medical Center "Preventclinic", LLC Kyiv Ukraine 03035
    114 Municipal Enterprise "Poltava Regional Clinical Infectious Hospital of Poltava Regional Council" Poltava Ukraine 36011
    115 University Hospital of Sumy State University Sumy Ukraine 40000
    116 Municipal non-profit enterprise " Vinnytsia city clinical hospital No. 1" Vinnytsia Ukraine 21029
    117 Royal London Hospital London Greater London United Kingdom E1 1BB
    118 Gartnavel General Hospital Glasgow Strathclyde United Kingdom G12 0YN

    Sponsors and Collaborators

    • Eiger BioPharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eiger BioPharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03719313
    Other Study ID Numbers:
    • EIG-LNF-011
    First Posted:
    Oct 25, 2018
    Last Update Posted:
    Oct 1, 2021
    Last Verified:
    Sep 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hepatitis D
    Hepatitis
    Interferons
    Ritonavir
    Interferon-alpha
    Peginterferon alfa-2a
    Interferon alpha-2
    Lonafarnib

    Study Results

    No Results Posted as of Oct 1, 2021