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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03719313




Registration number
NCT03719313
Ethics application status
Date submitted
18/10/2018
Date registered
25/10/2018
Date last updated
14/04/2023

Titles & IDs
Public title
Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a
Scientific 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)
Secondary ID [1] 0 0
EIG-LNF-011
Universal Trial Number (UTN)
Trial acronym
D-LIVR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis Delta Virus 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lonafarnib
Treatment: Drugs - Ritonavir
Treatment: Drugs - PEG IFN-alfa-2a
Treatment: Drugs - Placebo Lonafarnib
Treatment: Drugs - Placebo Ritonavir

Experimental: Group 1 - Lonafarnib 50 mg BID + Ritonavir 100 mg BID

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

Active Comparator: Group 3 - placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW

Placebo Comparator: Group 4 - placebo Lonafarnib + placebo Ritonavir


Treatment: Drugs: Lonafarnib
Lonafarnib (LNF) 50 mg BID

Treatment: Drugs: Ritonavir
Ritonavir (RTV) 100 mg BID

Treatment: Drugs: PEG IFN-alfa-2a
PEG IFN alfa-2a 180 mcg QW

Treatment: Drugs: Placebo Lonafarnib
Placebo

Treatment: Drugs: Placebo Ritonavir
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
48 weeks
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
48 weeks
Secondary outcome [1] 0 0
To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
48 weeks
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
48 weeks
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
48 weeks
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
48 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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-a (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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/03/2023
Sample size
Target
Accrual to date
Final
407
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Connecticut
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United States of America
State/province [3] 0 0
Florida
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United States of America
State/province [4] 0 0
Illinois
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United States of America
State/province [5] 0 0
Iowa
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United States of America
State/province [6] 0 0
Maryland
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United States of America
State/province [7] 0 0
Michigan
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United States of America
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New York
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United States of America
State/province [9] 0 0
Oklahoma
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United States of America
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Texas
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Belgium
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Antwerpen
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Belgium
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Bruxelles
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Belgium
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Edegem
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Belgium
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Liège
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Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Stara Zagora
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
France
State/province [20] 0 0
Alpes Maritimes
Country [21] 0 0
France
State/province [21] 0 0
Bas Rhin
Country [22] 0 0
France
State/province [22] 0 0
Gironde
Country [23] 0 0
France
State/province [23] 0 0
Hauts De Seine
Country [24] 0 0
France
State/province [24] 0 0
Isere
Country [25] 0 0
France
State/province [25] 0 0
Rhone
Country [26] 0 0
France
State/province [26] 0 0
Seine Saint Denis
Country [27] 0 0
France
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Val De Marne
Country [28] 0 0
Germany
State/province [28] 0 0
Baden Wuerttemberg
Country [29] 0 0
Germany
State/province [29] 0 0
Hessen
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Germany
State/province [30] 0 0
Niedersachsen
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Germany
State/province [31] 0 0
Nordrhein Westfalen
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Germany
State/province [32] 0 0
Berlin
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Germany
State/province [33] 0 0
Hamburg
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Greece
State/province [34] 0 0
Athens
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Israel
State/province [35] 0 0
Afula
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Israel
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Beer-Sheva
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Jerusalem
Country [39] 0 0
Israel
State/province [39] 0 0
Nahariya
Country [40] 0 0
Israel
State/province [40] 0 0
Ramat Gan
Country [41] 0 0
Italy
State/province [41] 0 0
Foggia
Country [42] 0 0
Italy
State/province [42] 0 0
Milano
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Italy
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Brescia
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Italy
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Messina
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Italy
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Modena
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Italy
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Napoli
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Italy
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Parma
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Italy
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Pisa
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Italy
State/province [49] 0 0
Roma
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Italy
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Torino
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Moldova, Republic of
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Chisinau
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Mongolia
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Ulaanbaatar
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New Zealand
State/province [53] 0 0
Grafton
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Pakistan
State/province [54] 0 0
Karachi
Country [55] 0 0
Romania
State/province [55] 0 0
Bucuresti
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Romania
State/province [56] 0 0
Cluj-Napoca
Country [57] 0 0
Russian Federation
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Chelyabinsk
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Russian Federation
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Krasnodar
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Russian Federation
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Moscow
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Russian Federation
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Novosibirsk
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Russian Federation
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Pyatigorsk
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Russian Federation
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Samara
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Russian Federation
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Stavropol
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Russian Federation
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Yakutsk
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Sweden
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Falun
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Sweden
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Huddinge
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Sweden
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Malmö
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Switzerland
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Bern
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Taiwan
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Changhua
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Taiwan
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Chia-Yi City
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Taiwan
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Taoyuan County
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Turkey
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Diyarbakir
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Turkey
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Istanbul
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Turkey
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Izmir
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Poltava
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Ukraine
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Sumy
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Ukraine
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Vinnytsia
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United Kingdom
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Greater London
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Strathclyde

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eiger BioPharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03719313
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/ct2/show/NCT03719313