A Phase 1 Dose-Ranging Study to Assess the Safety, Pharmacokinetics and Initial Antiviral Efficacy of NVR 3-778 in Healthy Volunteers and Patients With Chronic Hepatitis B
A Phase 1 Dose-Ranging Study to Assess the Safety, Pharmacokinetics and Initial Antiviral Efficacy of NVR 3-778 in Healthy Volunteers and Patients With Chronic Hepatitis B
This Phase 1 trial will assess the dose-related safety and PK profile of different doses of NVR 3-778, first in healthy volunteer subjects (part I) and subsequently in patients with chronic hepatitis B (part II). Additionally, in Part II, changes in patients' serum HBV DNA levels and other virologic efficacy parameters will be assessed.
The Part I (Phase 1a) assessments of the dose-related safety and PK of NVR 3-778 in volunteers will be conducted an established Phase 1 unit, which will facilitate the overnight confinements and frequent safety assessments and blood sampling required for the Part I evaluations. The Part II (Phase 1b) assessments of the dose-related safety, PK, and initial antiviral efficacy of NVR 3-778 in hepatitis B patients will also be conducted at approximately 14 different sites to meet enrollment goals of 54-84 chronic hepatitis B patients.
To promote objective safety and tolerance assessments during this trial, study subjects, and site personnel administering the study drug and performing the clinical assessments on the subjects, will be blinded to individual subjects' treatments assignments (active NVR 3-778 or placebo doses), for all treatment cohorts in the study. Study advancement to subsequent volunteer cohorts in Part I and subsequent patient cohorts in Part II will require satisfactory interim reviews of available cumulative safety data by the Part I and Part II Safety Review Committees (SRCs), using the safety criteria and review procedures described in the protocol. Also, there will be two interim reviews of safety data by an independent Safety Monitoring Board (SMB), as described in the protocol.
Healthy volunteers may be male or female between 18 and 65 years old with a BMI of 18-32kg/m2. They must be in good health not have any health condition which could interfere with the absorption, distribution or elimination of study drug, or with the clinical and laboratory assessments in this study.
Patients enrolling in Part II of the study, may be male or female between 18 and 65 years of age, with a BMI of 18-35kg/m2. Patients must have HBeAg positive, chronic hepatitis B with no history of clinical decompensation, and must not have been treated for hepatitis B before.