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Trial record 16 of 1273 for:    IFNA2

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 : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Eiger BioPharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 18, 2018
First Posted Date  ICMJE October 25, 2018
Last Update Posted Date August 13, 2019
Actual Study Start Date  ICMJE December 1, 2018
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03719313 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis Delta Virus
Intervention  ICMJE
  • 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
  • Drug: Placebo Lonafarnib
    Placebo
  • Drug: Placebo Ritonavir
    Placebo
Study Arms  ICMJE
  • Experimental: Group 1
    Lonafarnib 50 mg BID + Ritonavir 100 mg BID
    Interventions:
    • Drug: Lonafarnib
    • Drug: Ritonavir
  • Experimental: Group 2
    Lonafarnib 50 mg BID + Ritonavir 100 mg BID + PEG IFN alfa-2a 180 mcg QW
    Interventions:
    • Drug: Lonafarnib
    • Drug: Ritonavir
    • Drug: PEG IFN-alfa-2a
  • Active Comparator: Group 3
    placebo Lonafarnib + placebo Ritonavir + PEG IFN-alfa-2a 180 mcg QW
    Interventions:
    • Drug: PEG IFN-alfa-2a
    • Drug: Placebo Lonafarnib
    • Drug: Placebo Ritonavir
  • Placebo Comparator: Group 4
    placebo Lonafarnib + placebo Ritonavir
    Interventions:
    • Drug: Placebo Lonafarnib
    • Drug: Placebo Ritonavir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2018)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2021
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John Ferraro 650-272-6138 DLIVR@eigerbio.com
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Canada,   France,   Germany,   Greece,   Israel,   Italy,   Moldova, Republic of,   Mongolia,   New Zealand,   Pakistan,   Romania,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Vietnam
 
Administrative Information
NCT Number  ICMJE NCT03719313
Other Study ID Numbers  ICMJE EIG-LNF-011
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eiger BioPharmaceuticals
Study Sponsor  ICMJE Eiger BioPharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Eiger BioPharmaceuticals
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP