- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03673215
The Tolerability,Safety,PK/PD Study of rhTPO in the Patients With Liver Function Impairment
March 20, 2020 updated by: Shenyang Sunshine Pharmaceutical Co., LTD.
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.
Study Overview
Status
Unknown
Conditions
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 Type
Interventional
Enrollment (Anticipated)
58
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Quanrui WU, Master
- Phone Number: 86 10 84892211
- Email: wuquanrui@3sbio.com
Study Contact Backup
- Name: Sunqiong Cao, MD
- Phone Number: 86 10 84892211
- Email: caosunqiong@3sbio.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100039
- Recruiting
- 302 Military Hospital of China
-
Contact:
- Jinhua Hu, MD
-
Contact:
- Haibin Su, MD
- Email: suhaibin302@163.com
-
Principal Investigator:
- Jinhua HU, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: A
|
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
Other Names:
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.
Other Names:
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.
Other Names:
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.
Other Names:
|
EXPERIMENTAL: B1
|
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
Other Names:
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.
Other Names:
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.
Other Names:
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.
Other Names:
|
PLACEBO_COMPARATOR: B2
|
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
|
EXPERIMENTAL: C1-1
|
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
Other Names:
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.
Other Names:
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.
Other Names:
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.
Other Names:
|
PLACEBO_COMPARATOR: C1-2
|
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
|
EXPERIMENTAL: C2-1
|
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.
Other Names:
|
PLACEBO_COMPARATOR: C2-2
|
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
|
EXPERIMENTAL: C3-1
|
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
Other Names:
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.
Other Names:
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.
Other Names:
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.
Other Names:
|
PLACEBO_COMPARATOR: C3-2
|
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.).
|
Up to 29 days
|
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]).
|
For 9 days
|
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]).
|
For 9 days
|
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-∞]). |
For 9 days
|
Cmax of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Observed maximum plasma concentration(Cmax).
|
For 9 days
|
tmax of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Time to Cmax (tmax).
|
For 9 days
|
t1/2 of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Elimination half-life (t1/2).
|
For 9 days
|
MRT for rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Mean residence time (MRT).
|
For 9 days
|
Kel of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Elimination rate constant (Kel).
|
For 9 days
|
Vd of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:Apparent volume of distribution(Vd).
|
For 9 days
|
CL/F of rhTPO
Time Frame: For 9 days
|
To assess plasma rhTPO PK Parameter:apparent clearance (CL/F).
|
For 9 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunogenicity of rhTPO
Time Frame: Up to 12 months
|
To evaluate the incidence of anti-rhTPO antibodies and neutralizing antibodies
|
Up to 12 months
|
Change of Platelet count (PLT)
Time Frame: Up to 29 days
|
To evaluate the changing curve of platelet count (PLT) in each arm of subjects
|
Up to 29 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
June 28, 2018
Primary Completion (ANTICIPATED)
October 8, 2020
Study Completion (ANTICIPATED)
December 31, 2020
Study Registration Dates
First Submitted
August 15, 2018
First Submitted That Met QC Criteria
September 13, 2018
First Posted (ACTUAL)
September 17, 2018
Study Record Updates
Last Update Posted (ACTUAL)
March 23, 2020
Last Update Submitted That Met QC Criteria
March 20, 2020
Last Verified
March 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3SBio-TPO-106
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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