Clinical trial NCT02288208: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatitis B
Lead sponsor: TetraLogic Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-11-11
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: From Screening through end of study, up to 13 weeks
Secondary outcomes:
measure: 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
timeFrame: Day -1 through Day 26
measure: Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)
timeFrame: Day -1 through Day 26
measure: 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
timeFrame: Day -1, Day 1 and Day 22
measure: Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)
timeFrame: Screening through Day 29
measure: 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
timeFrame: Screening through Day 29
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX / Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Nucleus Network Limited / AMREP Precinct
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
Study officials:
References: