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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02288208
Recruitment Status : Terminated (Due to cranial nerve palsies observed)
First Posted : November 11, 2014
Last Update Posted : February 5, 2016
Information provided by (Responsible Party):
TetraLogic Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Hepatitis B Drug: Antiviral Therapy (tenofovir or entecavir) Drug: Birinapant Drug: Placebo (for birinapant) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : November 2014
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

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)

Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: From Screening through end of study, up to 13 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb) [ Time Frame: Screening through Day 29 ]
    Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb

  5. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02288208

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

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Responsible Party: TetraLogic Pharmaceuticals Identifier: NCT02288208     History of Changes
Other Study ID Numbers: TL32711-POC-0095-PTL
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: February 5, 2016
Last Verified: February 2016
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents