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About
An Open-label, Dose-ranging Study to Evaluate the Safety and Efficacy of Lonafarnib with Ritonavir Boosting +/- Peginterferon alfa-2a in Patients Chronically Infected with Delta Hepatitis (HDV) (LOWR-2).
Full description
Chronic delta hepatitis is a serious form of chronic liver disease caused by infection with the hepatitis D virus (HDV), a small RNA virus that requires farnesylation of its major structural protein (HDV antigen) for replication. Up to sixty subjects with chronic delta hepatitis will be randomized to receive one of ten different doses of lonafarnib. Dosing will occur over 12-48 weeks, and during that time, evidence of antiviral response will be assessed by frequent measurements of HDV-RNA. The primary therapeutic endpoint will be an improvement in quantitative serum HDV RNA levels after treatment with lonafarnib therapy. The primary safety endpoint will be the ability to tolerate the drug at the prescribed dose for the treatment duration. Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms. Therapy will be stopped for intolerance to lonafarnib. This study is designed as a Phase 2a study assessing the safety, tolerance and antiviral activity of nine dosing combinations of lonafarnib with ritonavir boosting with and without peginterferon alfa-2a (PEG IFN-a).
Enrollment
Sex
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Volunteers
Inclusion criteria
Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR
Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry
Liver biopsy within the last two years (biopsy can be done at the Screening Visit)
Positive viral load of >100,000 copies/mL as measured by quantitative PCR
Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval <450 milliseconds - using Bazett's correction
Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study:
Willing and able to comply with study procedures and provide written informed consent
Exclusion criteria
Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1
Patients co-infected with HIV
Patients with screening tests positive for HCV, or anti-HIV Ab
History of decompensated cirrhosis within the past year
Active jaundice defined by total bilirubin > 2.0 excluding Gilbert's disease
INR ≥ 1.5
Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (> 20 g per day for females (1.5 standard alcohol drinks) or > 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL)
Drug abuse within the last six months with the exception of cannabinoids and their derivatives
Patients with absolute neutrophil count (ANC) < 1500 cells/mm^3; platelet count < 100,000 cells/mm^3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN)
History or clinical evidence of any of the following:
Patients with a body mass index > 30 kg/m^2
Concomitant drugs known to prolong the QT interval
Primary purpose
Allocation
Interventional model
Masking
55 participants in 10 patient groups
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Data sourced from clinicaltrials.gov
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