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

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ClinicalTrials.gov Identifier: NCT03719313
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : June 18, 2020
Sponsor:
Information provided by (Responsible Party):
Eiger BioPharmaceuticals

Study Description
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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
Hepatitis Delta Virus Drug: Lonafarnib Drug: Ritonavir Drug: PEG IFN-alfa-2a Drug: Placebo Lonafarnib Drug: Placebo Ritonavir 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : December 1, 2018
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis

Arms and Interventions
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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
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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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 48 weeks ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719313


Contacts
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Contact: Sue Speyer 650-272-6138 DLIVR@eigerbio.com

Locations
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Sponsors and Collaborators
Eiger BioPharmaceuticals
More Information
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Responsible Party: Eiger BioPharmaceuticals
ClinicalTrials.gov Identifier: NCT03719313    
Other Study ID Numbers: EIG-LNF-011
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis D
Hepatitis
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Liver Diseases
Digestive System Diseases
Interferons
Ritonavir
Interferon-alpha
Peginterferon alfa-2a
Interferon alpha-2
Lonafarnib
 Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs