Hepatitis BPhase 1NCT02288208
Phase I Safety and Tolerability Study of Birinapant in Chronic Hepatitis B
A Phase 1 study testing Antiviral Therapy (tenofovir or entecavir) and Birinapant in people with Hepatitis B, run by TetraLogic Pharmaceuticals at 3 sites in Australia.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Antiviral Therapy (tenofovir or entecavir) and Birinapant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 3 sitesAustralia
- Study dates
- Nov 2014to May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Australia3 sites
CMAX / Royal Adelaide Hospital
Adelaide, South Australia, 5000
Nucleus Network Limited / AMREP Precinct
Melbourne, Victoria, 3004
Linear Clinical Research Ltd
Nedlands, Western Australia, 6009
About this study
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
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.
- Conditions
- Hepatitis B
- Being tested
- Antiviral Therapy (tenofovir or entecavir), Birinapant, Placebo (for birinapant)
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antiviral Therapy (tenofovir or entecavir)Drug
BirinapantDrug
Placebo (for birinapant)Drug
| Study group | Role | What they receive |
|---|---|---|
| Antiviral Therapy & Birinapant | Experimental | 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. Receives: Drug: Antiviral Therapy (tenofovir or entecavir); Drug: Birinapant |
| Antiviral Therapy & Placebo | Placebo comparator | 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. Receives: Drug: Antiviral Therapy (tenofovir or entecavir); Drug: Placebo (for birinapant) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Measured: From Screening through end of study, up to 13 weeks
Secondary outcomes (5)
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
Measured: 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)
Measured: 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
Measured: Day -1, Day 1 and Day 22
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)
Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb
Measured: Screening through Day 29
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
Measured: Screening through Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2014 (estimated)
- Study startNov 2014
- Primary completionMay 2015
- Study completionMay 2015
Why it stopped: Due to cranial nerve palsies observed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- TetraLogic Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02288208
- Sponsor's protocol ID
- TL32711-POC-0095-PTL
- Status last verified
- Feb 2016
- First submitted
- 3 Nov 2014
- Last updated
- 5 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02288208
- Acronym / sponsor ID
- TL32711-POC-0095-PTL
- Conditions
- Hepatitis B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to cranial nerve palsies observed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- TetraLogic PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 11 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antiviral Therapy & Birinapant | Experimental | Drug: Antiviral Therapy (tenofovir or entecavir), Drug: BirinapantAntiviral 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. |
| Antiviral Therapy & Placebo | Placebo comparator | Drug: Antiviral Therapy (tenofovir or entecavir), Drug: Placebo (for birinapant)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antiviral Therapy (tenofovir or entecavir) | Drug | Antiviral Therapy & Birinapant, Antiviral Therapy & Placebo |
| Birinapant | Drug | Antiviral Therapy & Birinapant |
| Placebo (for birinapant) | Drug | Antiviral Therapy & Placebo |
Primary outcome
Number of participants with adverse events
Time frame: From Screening through end of study, up to 13 weeks
5 secondary outcomes
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
Time frame: 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)
Time frame: 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
Time frame: Day -1, Day 1 and Day 22
Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)
Time frame: Screening through Day 29
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
Time frame: Screening through Day 29
Results and safety
The study was stopped early (reason given: Due to cranial nerve palsies observed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antiviral Therapy (tenofovir or entecavir) and Birinapant in people with Hepatitis B, run by TetraLogic Pharmaceuticals at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to cranial nerve palsies observed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: From Screening through end of study, up to 13 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2016.