Phase I Safety and Tolerability Study of Birinapant in Chronic Hepatitis B

Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Birinapant in Subjects With Chronic Hepatitis B

This study evaluates the addition of birinapant in subjects with chronic Hepatitis B who are currently receiving anti-viral therapy with either tenofovir or entecavir. Patients will receive either birinapant or placebo in addition to their anti-viral therapy.

Study Overview

• Status: Terminated
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Antiviral Therapy (tenofovir or entecavir); Drug: Birinapant; Drug: Placebo (for birinapant)

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX / Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Limited / AMREP Precinct
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented history of chronic Hepatitis B infection currently being treated with tenofovir or entecavir for at least 3 months
• Measurable titer of HBsAg
• HBV DNA level < 2 log copies/mL or 10² copies/mL
• No more than Child-Pugh score of 5 plus a valid FibroScan® of at least 10 readings with a median score of <7 and interquartile range of < 30%
• Adequate liver function, aspartate AST and ALT ≤2 x ULN
• Adequate renal function as evidenced by creatinine ≤2 mg/dL

Exclusion Criteria:

• Participation in any interventional study within 4 weeks prior to Screening
• Known HIV infection, Hepatitis C, or other significant hepatic disorder including cirrhosis (Child-Pugh Class B or C)
• Serious illness or autoimmune disease or other known liver disease
• Uncontrolled hypertension
• Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications, or clinically significant cardiac disease
• Currently breast feeding, pregnant or planning on becoming pregnant
• Known allergy or hypersensitivity to any of the formulation components of birinapant or placebo, including citric acid
• History of cranial nerve palsy
• Current treatment with anti-TNF therapies or has received treatment with anti-TNF therapies within the last 6 months
• Use of non-steroidal anti-inflammatory drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antiviral Therapy & Birinapant; Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and birinapant administered as a 30 minute IV infusion once weekly for four weeks.	Drug: Antiviral Therapy (tenofovir or entecavir); Drug: Birinapant
Placebo Comparator: Antiviral Therapy & Placebo; Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and placebo (for birinapant) administered as a 30 minute infusion once weekly for four weeks.	Drug: Antiviral Therapy (tenofovir or entecavir); Drug: Placebo (for birinapant)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	From Screening through end of study, up to 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of birinapant (in plasma): maximum concentration (Cmax), time of maximum concentration (Tmax), area under the curve (AUC) extrapolated to time infinity, AUC from dosing to last quantifiable concentration		Day -1 through Day 26
Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)		Day -1 through Day 26
Pharmacokinetics of oral antiviral medication (tenofovir or entecavir): Cmax, Tmax, AUC from dosing to last quantifiable concentration, t1/2, CL, terminal disposition rate constant, Vdss		Day -1, Day 1 and Day 22
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)	Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb	Screening through Day 29
Pharmacodynamic effect of birinapant on cIAP1 and cIAP2 levels in peripheral blood mononuclear cells (PBMC) and levels of cluster of differentiation 4 and 8 (CD4+, CD+8) lymphocytes		Screening through Day 29

Collaborators and Investigators

• Sponsor: TetraLogic Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: November 3, 2014
• First Submitted That Met QC Criteria: November 6, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir; Antiviral Agents
• Other Study ID Numbers: TL32711-POC-0095-PTL