Dose-Ranging Study to Assess the Safety, PK and Initial Antiviral Efficacy of NVR 3-778 in Chronic HBV Patients

Study Overview
=================
Brief Summary
-----------------
This Phase 1b trial will assess the dose-related safety and PK profile of different doses of NVR 3-778 in patients with chronic hepatitis B. Additionally,changes in patients' serum HBV DNA levels and other virologic efficacy parameters will be assessed.

Detailed Description
-----------------
The 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 patient cohorts will require satisfactory interim reviews of available cumulative safety data by the Safety Review Committees (SRC), using the safety criteria and review procedures described in the protocol. Also, there will be one interim review of safety data by an independent Safety Monitoring Board (SMB), as described in the protocol.

Official Title
-----------------
A Phase 1b Dose-Ranging Study to Assess the Safety, Pharmacokinetics and Initial Antiviral Efficacy of NVR 3-778 in Patients With HBeAg-Positive Chronic Hepatitis B Virus Infection

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: NVR 3-778
* Drug: Placebo for NVR 3-778
* Drug: Pegasys


Participation Criteria
=================
Eligibility Criteria
-----------------
Patients may be male or female between 18 and 65 years of age, with a BMI of 18-35kg/m2. Patients must be HBeAg positive and have chronic hepatitis B with no history of clinical decompensation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVR 3-778<br>NVR 3-778 in varying doses of capsules by mouth for 28 days | Drug: NVR 3-778<br> <br> |
| Placebo Comparator: Placebo for NVR 3-778<br>Placebo for NVR 3-778 in varying doses of capsules by mouth for 28 days | Drug: Placebo for NVR 3-778<br>* Sugar pill manufactured to mimic the NVR 3-778 capsule<br>|
| Experimental: NVR 3-778 and Pegasys<br>NVR 3-778 and Pegasys in combination in a yet to be determined dose by mouth and subcutaneous injection for 28 days | Drug: NVR 3-778<br> <br> Drug: Pegasys<br> <br> * Other names: peginterferon alfa-2a;|
| Active Comparator: Pegasys<br>Pegasys alone in a yet to be determined dose by subcutaneous injection for 28 days | Drug: Pegasys<br> <br> * Other names: peginterferon alfa-2a;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compared with baseline, decline of serum HBV-DNA in the value |  | Up to 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis B