Conditions: Chronic Hepatitis D Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 21
Healthy volunteers: no

Brief summary:
To Evaluate the Safety and Efficacy of Lonafarnib with and without Ritonavir Boosting in Adults With Genotype 1 Chronic Hepatitis D Virus (HDV) Infection (LOWR-1).

Detailed 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. Twenty-one subjects with chronic delta hepatitis will be randomized to receive one of seven different doses of lonafarnib. Dosing will occur over 4-12 weeks, depending on treatment arm, 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 seven dose combinations of lonafarnib with and without ritonavir boosting.

Arms:
arm 1: lonafarnib 200 mg BID; n=3 arm 2: lonafarnib 300 mg BID; n=3 arm 3: lonafarnib 100 mg TID; n=3 arm 4: lonafarnib 100 mg BID + PEG IFN-a 180 ug QW; n=3 arm 5: lonafarnib 200 mg BID + PEG IFN-a 180 ug QW; n=3 arm 6: lonafarnib 300 mg BID + PEG IFN-a 180 ug QW; n=2 arm 7: lonafarnib 100 mg BID + ritonavir 100 mg QD; n=3

Interventions: intervention 1: lonafarnib intervention 2: peginterferon alfa-2a intervention 3: ritonavir
Intervention descriptions: intervention 1: antiviral farnesyl transferase inhibitor intervention 2: immunomodulator intervention 3: CYP 3A4 inhibitor, lonafarnib booster

Protocol document: