Safety and Efficacy Study of NVR 3-778 in Healthy Volunteers and Hepatitis B Patients
Safety and Efficacy Study of NVR 3-778 in Healthy Volunteers and Hepatitis B Patients
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.