Hepatitis B
Conditions
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.
Interventions
Sponsors
TetraLogic Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events | From Screening through end of study, up to 13 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | Screening through Day 29 | — |
Countries
Australia
Outcome results
None listed