Study of the Efficacy and Safety of Lonafarnib / Ritonavir With and Without Pegylated Interferon -Alfa-2a
a study on Hepatitis D Hepatitis
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at UC Davis UCSF
- Dates
- study startedestimated completion
Description
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.
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)
Details
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.
Keywords
Hepatitis Delta Virus, Hepatitis D, Hepatitis, Interferons, Ritonavir, Interferon-alpha, Peginterferon alfa-2a, Interferon alpha-2, Lonafarnib, PEG IFN-alfa-2a
Eligibility
You can join if…
Open to people ages 18 years and up
- 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.
- 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.
- Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.
- Baseline liver biopsy demonstrating evidence of chronic hepatitis.
- ECGs demonstrating no acute ischemia or clinically significant abnormality.
- Normal dilated retinal examination.
You CAN'T join if...
General Exclusions
- Previous use of LNF within 12 months.
- Current or previous history of decompensated liver disease.
- Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable HIV RNA and HCV RNA, respectively.
- Evidence of significant portal hypertension.
- Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy.
- History of hepatocellular carcinoma.
- Patients with any of the following:
- Current eating disorder
- Evidence of alcohol substance use disorder.
- Drug abuse within the previous 6 months before screening.
- 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.
- Other significant medical condition that may require intervention during the study.
- Any condition that may impact proper absorption.
- 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.
- Use of heparin or warfarin.
- Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV.
- Receipt of systemic immunosuppressive therapy.
- History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG IFN-alfa-2a, tenofovir or entecavir.
Locations
- UCSF Fresno
Fresno California 93701 United States - University of California Davis Health System
Sacramento California 95817 United States - Ruane Clinical Research Group Inc.
Los Angeles California 90036 United States - Asia Pacific Liver Center
Los Angeles California 90057 United States - Kaiser Permanente Medical Center Sacramento
Sacramento California 95825 United States - Stanford University
Palo Alto California 94303 United States
Details
- Status
- in progress, not accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Eiger BioPharmaceuticals
- ID
- NCT03719313
- Phase
- Phase 3 research study
- Study Type
- Interventional
- Participants
- Expecting 400 study participants
- Last Updated