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

Primary Purpose

Hepatitis B

Status
Terminated
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Antiviral Therapy (tenofovir or entecavir)
Birinapant
Placebo (for birinapant)
Sponsored by
TetraLogic Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CMAX / Royal Adelaide Hospital
  • Nucleus Network Limited / AMREP Precinct
  • Linear Clinical Research Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Antiviral Therapy & Birinapant

Antiviral Therapy & Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of participants with adverse events

Secondary Outcome Measures

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
Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)
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
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)
Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb
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

Full Information

First Posted
November 3, 2014
Last Updated
February 4, 2016
Sponsor
TetraLogic Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02288208
Brief Title
Phase I Safety and Tolerability Study of Birinapant in Chronic Hepatitis B
Official Title
Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Birinapant in Subjects With Chronic Hepatitis B
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Due to cranial nerve palsies observed
Study Start Date
November 2014 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TetraLogic Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Antiviral Therapy & Birinapant
Arm Type
Experimental
Arm Description
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.
Arm Title
Antiviral Therapy & Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Antiviral Therapy (tenofovir or entecavir)
Intervention Type
Drug
Intervention Name(s)
Birinapant
Intervention Type
Drug
Intervention Name(s)
Placebo (for birinapant)
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
From Screening through end of study, up to 13 weeks
Secondary Outcome Measure Information:
Title
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
Time Frame
Day -1 through Day 26
Title
Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)
Time Frame
Day -1 through Day 26
Title
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
Time Frame
Day -1, Day 1 and Day 22
Title
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)
Description
Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb
Time Frame
Screening through Day 29
Title
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
Time Frame
Screening through Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
CMAX / Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Nucleus Network Limited / AMREP Precinct
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Linear Clinical Research Ltd
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia

12. IPD Sharing Statement

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

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