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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02288208




Registration number
NCT02288208
Ethics application status
Date submitted
3/11/2014
Date registered
11/11/2014
Date last updated
5/02/2016

Titles & IDs
Public title
Phase I Safety and Tolerability Study of Birinapant in Chronic Hepatitis B
Scientific title
Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Birinapant in Subjects With Chronic Hepatitis B
Secondary ID [1] 0 0
TL32711-POC-0095-PTL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Antiviral Therapy (tenofovir or entecavir)
Treatment: Drugs - Birinapant
Treatment: Drugs - Placebo (for birinapant)

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.

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.


Treatment: Drugs: Antiviral Therapy (tenofovir or entecavir)


Treatment: Drugs: Birinapant


Treatment: Drugs: Placebo (for birinapant)


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events
Timepoint [1] 0 0
From Screening through end of study, up to 13 weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Day -1 through Day 26
Secondary outcome [2] 0 0
Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)
Timepoint [2] 0 0
Day -1 through Day 26
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Day -1, Day 1 and Day 22
Secondary outcome [4] 0 0
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb) - Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb
Timepoint [4] 0 0
Screening through Day 29
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Screening through Day 29

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
CMAX / Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Nucleus Network Limited / AMREP Precinct - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
TetraLogic Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02288208
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02288208