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

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02288208
• Other study ID #: TL32711-POC-0095-PTL
• Status: Terminated
• Phase: Phase 1
• First received: November 3, 2014
• Last updated: February 4, 2016
• Start date: November 2014
• Est. completion date: May 2015

Study information

• Verified date: February 2016
• Source: TetraLogic Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationNew Zealand: Medsafe
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Antiviral Therapy (tenofovir or entecavir)

• Birinapant

• Placebo (for birinapant)

Locations

Country	Name	City	State
Australia	CMAX / Royal Adelaide Hospital	Adelaide	South Australia
Australia	Nucleus Network Limited / AMREP Precinct	Melbourne	Victoria
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia

Sponsors (1)

Lead Sponsor	Collaborator
TetraLogic Pharmaceuticals

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		From Screening through end of study, up to 13 weeks	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No