Liver CirrhosisEarly Phase 1NCT03673215
The Tolerability，Safety，PK/PD Study of rhTPO in the Patients With Liver Function Impairment
A Early Phase 1 study testing Recombinant human thrombopoietin in people with Liver Cirrhosis, run by Shenyang Sunshine Pharmaceutical Co., LTD. at 1 site in China.
Trial summary
The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin in the patients with different degree of liver function impairment according Child- Pugh class. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Recombinant human thrombopoietin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteChina
- Study dates
- 28 Jun 2018to 31 Dec 2020
- Phase
- Early 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Patients with cirrhosis caused by chronic liver disease who have been diagnosed by biopsy/imaging (Child-Pugh class A, B, and C).
- 2. Life expectancy≥3 months.
- 3. Platelet count≤80×109/ L.
- 4. Fertile female subjects with a negative pregnancy test during the screening period and who agree to take effective contraceptive methods Throughout the study period will be eligible for this study.
- 5. Voluntary written informed consent.
Who cannot join
- 1 Subjects allergic to any component of investigational drug.
- 2 Subjects with cirrhosis caused by drug-induced liver injury.
- 3 Subjects with history of splenectomy or liver transplantation.
- 4 Liver cirrhosis with serious complications, including: hepatic encephalopathy, intractable ascites, upper gastrointestinal bleeding, etc.
- 5 Subjects with Liver failure.
- 6 Tthe presence of portal vein thrombosis or tumor thrombus was indicated by doppler ultrasound or CT or MRI and other imaging examinations within 3 months prior to the beginning of screening.
Show all 21Show fewer
- 7 Subjects with history of arterial or venous thromboembolism, or with thromboembolic disease, or with high risk factors for thrombosis, or with a hereditary tendency to thrombosis, including Antithrombin III deficiency, etc.
- 8 Subjects with history of any disease other than chronic liver disease and cirrhosis that may result in decreased platelet count and/or abnormal platelet function, including aplastic anemia, myelodysplastic syndrome (MDS), bone marrow fibrosis, etc.;
- 9 Subjects with diseases with higher bleeding risk, such as coagulation factor deficiency or Vascular pseudohemophilia factor deficiency.
- 10 Subjects with severe infections that are not effectively controlled.
- 11 Past or present history with any serious disease except liver disease, including: angina, severe arrhythmia, myocardial infarction, heart failure, Cerebral hemorrhage, cerebral infarction, intracranial infection, Renal insufficiency( creatinine clearance rate ≤50 mL/min )，as well as any other diseases that have been judged by investigator to be unsuitable for this study.
- 12 Subjects who had undergone trans jugular intrahepatic portal shunt (TIPS);
- 13 Subjects with Anti-HIV positive antibodies or Anti- TPHA positive antibodies.
- 14 Subjects who received any therapy with increased platelet count within the 3 weeks or platelet transfusion within 2 weeks before randomization.
- 15 No more than 30 days or 5 half-lives after investigational drug treatment for other studies (whichever is longer).
- 16 Subjects with history of primary liver cancer, or an other malignant tumor.
- 17 patients with WHO≥grade 2 of existing active bleeding, or with history of active bleeding within 2 weeks before randomization.
- 18 Pregnant or breast-feeding women.
- 19 Women who have a pregnancy plan within 3 months.
- 20 Subjects with history of drug abuse and alcoholism within 6 months prior to enrollment.
- 21 Subjects who do not have the sufficient ability of understanding，communication and cooperation leading to failure to ensure compliance with protocol will be excluded.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
302 Military Hospital of China
Beijing, Beijing Municipality, 100039
Jinhua Hu, MD
Haibin Su, MD, suhaibin302@163.com
About this study
Official title: A Phase Ia Dose-escalation Study to Access the Tolerability，Safety，Pharmacokinetics and Pharmacodynamics of Recombinant Human Thrombopoietin in the Patients With Different Degree of Liver Function Impairment
The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin in the patients with different degree of liver function impairment according Child- Pugh class.
Read the detailed description
This is a randomized, double-blind, placebo controlled, dose-escalation phase Ia study to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin. According Child- Pugh class of liver function impairment and different dose of recombinant human thrombopoietin, nine arms be designed in this study. Each subject in Arm A will be only administered recombinant human thrombopoietin. Each subject in Arm B and C will be randomly assigned to accept either recombinant human thrombopoietin or placebo in 5:1 ratio.
- Conditions
- Liver Cirrhosis
- Being tested
- Recombinant human thrombopoietin, Placebo
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human thrombopoietinDrug
Also called rhTPO
Recombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class A
Recombinant human thrombopoietinDrug
Also called rhTPO
Recombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
PlaceboDrug
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
Recombinant human thrombopoietinDrug
Also called rhTPO
Recombinant human thrombopoietin will be administered single dose 150 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C.
PlaceboDrug
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
recombinant human thrombopoietinDrug
Also called rhTPO
Recombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C.
placeboDrug
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
Recombinant human thrombopoietinDrug
Also called rhTPO
Recombinant human thrombopoietin will be administered single dose 450 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C.
placeboDrug
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: Recombinant human thrombopoietin |
| B1 | Experimental | Not described Receives: Drug: Recombinant human thrombopoietin |
| B2 | Placebo comparator | Not described Receives: Drug: Placebo |
| C1-1 | Experimental | Not described Receives: Drug: Recombinant human thrombopoietin |
| C1-2 | Placebo comparator | Not described Receives: Drug: Placebo |
| C2-1 | Experimental | Not described Receives: Drug: recombinant human thrombopoietin |
| C2-2 | Placebo comparator | Not described Receives: Drug: placebo |
| C3-1 | Experimental | Not described Receives: Drug: Recombinant human thrombopoietin |
| C3-2 | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by the collection of adverse events
To evaluate the adverse events (incidence, severity, outcome, causality with the investigational drug, etc.).
Measured: Up to 29 days
AUC[0-24]of rhTPO
To assess plasma rhTPO Pharmacokinetic (PK) Parameter: Area under the concentration-time curve from time zero extrapolated to 24 hours(AUC [0-24]).
Measured: For 9 days
AUC [0-t] of rhTPO
To assess plasma rhTPO PK Parameter: Area under the concentration-time curve from time zero to last time of quantifiable concentration(AUC [0-t]).
Measured: For 9 days
AUC [0-∞]of rhTPO
To assess plasma rhTPO PK Parameter:
area under the concentration-time curve from time zero extrapolated to infinity(AUC [0-∞]).
Measured: For 9 days
Cmax of rhTPO
To assess plasma rhTPO PK Parameter：Observed maximum plasma concentration(Cmax).
Measured: For 9 days
tmax of rhTPO
To assess plasma rhTPO PK Parameter：Time to Cmax (tmax).
Measured: For 9 days
t1/2 of rhTPO
To assess plasma rhTPO PK Parameter：Elimination half-life (t1/2).
Measured: For 9 days
MRT for rhTPO
To assess plasma rhTPO PK Parameter：Mean residence time (MRT).
Measured: For 9 days
Kel of rhTPO
To assess plasma rhTPO PK Parameter：Elimination rate constant （Kel）.
Measured: For 9 days
Vd of rhTPO
To assess plasma rhTPO PK Parameter：Apparent volume of distribution（Vd）.
Measured: For 9 days
CL/F of rhTPO
To assess plasma rhTPO PK Parameter：apparent clearance (CL/F).
Measured: For 9 days
Secondary outcomes (2)
Immunogenicity of rhTPO
To evaluate the incidence of anti-rhTPO antibodies and neutralizing antibodies
Measured: Up to 12 months
Change of Platelet count (PLT)
To evaluate the changing curve of platelet count (PLT) in each arm of subjects
Measured: Up to 29 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start28 Jun 2018
- Primary completion8 Oct 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Shenyang Sunshine Pharmaceutical Co., LTD.The sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenyang Sunshine Pharmaceutical Co., LTD.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03673215
- Sponsor's protocol ID
- 3SBio-TPO-106
- Status last verified
- Mar 2020
- First submitted
- 15 Aug 2018
- Last updated
- 23 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ia Dose-escalation Study to Access the Tolerability，Safety，Pharmacokinetics and Pharmacodynamics of Recombinant Human Thrombopoietin in the Patients With Different Degree of Liver Function Impairment
- ClinicalTrials.gov ID
- NCT03673215
- Acronym / sponsor ID
- 3SBio-TPO-106
- Conditions
- Liver Cirrhosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Shenyang Sunshine Pharmaceutical Co., LTD.Industry (pharma, biotech, devices)
- Study start
- 28 Jun 2018 (actual)
- Primary completion
- 8 Oct 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 17 Sep 2018 (actual)
- 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.
The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin in the patients with different degree of liver function impairment according Child- Pugh class.
Detailed description
This is a randomized, double-blind, placebo controlled, dose-escalation phase Ia study to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin. According Child- Pugh class of liver function impairment and different dose of recombinant human thrombopoietin, nine arms be designed in this study. Each subject in Arm A will be only administered recombinant human thrombopoietin. Each subject in Arm B and C will be randomly assigned to accept either recombinant human thrombopoietin or placebo in 5:1 ratio.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Recombinant human thrombopoietin |
| B1 | Experimental | Drug: Recombinant human thrombopoietin |
| B2 | Placebo comparator | Drug: Placebo |
| C1-1 | Experimental | Drug: Recombinant human thrombopoietin |
| C1-2 | Placebo comparator | Drug: Placebo |
| C2-1 | Experimental | Drug: recombinant human thrombopoietin |
| C2-2 | Placebo comparator | Drug: placebo |
| C3-1 | Experimental | Drug: Recombinant human thrombopoietin |
| C3-2 | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 1. Patients with cirrhosis caused by chronic liver disease who have been diagnosed by biopsy/imaging (Child-Pugh class A, B, and C).
- 2. Life expectancy≥3 months.
- 3. Platelet count≤80×109/ L.
- 4. Fertile female subjects with a negative pregnancy test during the screening period and who agree to take effective contraceptive methods Throughout the study period will be eligible for this study.
- 5. Voluntary written informed consent.
Key exclusion criteria (21 listed)
- 1 Subjects allergic to any component of investigational drug.
- 2 Subjects with cirrhosis caused by drug-induced liver injury.
- 3 Subjects with history of splenectomy or liver transplantation.
- 4 Liver cirrhosis with serious complications, including: hepatic encephalopathy, intractable ascites, upper gastrointestinal bleeding, etc.
- 5 Subjects with Liver failure.
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 |
|---|---|---|
| Recombinant human thrombopoietinAlso: rhTPORecombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class A | Drug | A |
| Recombinant human thrombopoietinAlso: rhTPORecombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B. | Drug | B1 |
| PlaceboPlacebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B. | Drug | B2 |
| Recombinant human thrombopoietinAlso: rhTPORecombinant human thrombopoietin will be administered single dose 150 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C. | Drug | C1-1 |
| PlaceboPlacebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C | Drug | C1-2 |
| recombinant human thrombopoietinAlso: rhTPORecombinant human thrombopoietin will be administered single dose 300 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C. | Drug | C2-1 |
| placeboPlacebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C | Drug | C2-2 |
| Recombinant human thrombopoietinAlso: rhTPORecombinant human thrombopoietin will be administered single dose 450 U/Kg subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C. | Drug | C3-1 |
| placeboPlacebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C | Drug | C3-2 |
Primary outcome
Safety and tolerability as assessed by the collection of adverse events
Time frame: Up to 29 days
To evaluate the adverse events (incidence, severity, outcome, causality with the investigational drug, etc.).
AUC[0-24]of rhTPO
Time frame: For 9 days
To assess plasma rhTPO Pharmacokinetic (PK) Parameter: Area under the concentration-time curve from time zero extrapolated to 24 hours(AUC [0-24]).
AUC [0-t] of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter: Area under the concentration-time curve from time zero to last time of quantifiable concentration(AUC [0-t]).
AUC [0-∞]of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter: area under the concentration-time curve from time zero extrapolated to infinity(AUC [0-∞]).
Cmax of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Observed maximum plasma concentration(Cmax).
tmax of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Time to Cmax (tmax).
t1/2 of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Elimination half-life (t1/2).
MRT for rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Mean residence time (MRT).
Kel of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Elimination rate constant （Kel）.
Vd of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：Apparent volume of distribution（Vd）.
CL/F of rhTPO
Time frame: For 9 days
To assess plasma rhTPO PK Parameter：apparent clearance (CL/F).
2 secondary outcomes
Immunogenicity of rhTPO
Time frame: Up to 12 months
Change of Platelet count (PLT)
Time frame: Up to 29 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2020.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Recombinant human thrombopoietin in people with Liver Cirrhosis, run by Shenyang Sunshine Pharmaceutical Co., LTD. at 1 site in China.
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 5 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Quanrui WU, Master (86 10 84892211, wuquanrui@3sbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability as assessed by the collection of adverse events (time frame: Up to 29 days). The study lists 11 primary outcomes in all. 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 23 Mar 2020.