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

NCT02288208 | Terminated Phase 1

• 1 other identifier: TL32711-POC-0095-PTL
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

  From Screening through end of study, up to 13 weeks

Secondary Outcomes (5)

• 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)

  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

Study Arms (2)

Antiviral Therapy & Birinapant

EXPERIMENTAL

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

Antiviral Therapy & Placebo

PLACEBO COMPARATOR

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)

Interventions

Antiviral Therapy (tenofovir or entecavir) DRUG

Antiviral Therapy & Birinapant; Antiviral Therapy & Placebo

Birinapant DRUG

Antiviral Therapy & Birinapant

Placebo (for birinapant) DRUG

Antiviral Therapy & Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TetraLogic Pharmaceuticals: lead

Study Sites (3)

CMAX / Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Nucleus Network Limited / AMREP Precinct

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research Ltd

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

Tenofovir; entecavir; birinapant

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 11, 2014
• Study Start: November 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: February 5, 2016

Record last verified: 2016-02

Locations

AU (3)