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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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)
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
Sex
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
1/11/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2015
Sample size
Target
Accrual to date
Final
7
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/ct2/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/ct2/show/NCT02288208