The Tolerability，Safety，PK/PD Study of rhTPO in the Patients With Liver Function Impairment

NCT ID: NCT03673215

Last Updated: 2020-03-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-28
• Study Completion Date: 2020-12-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A

Group Type: EXPERIMENTAL

Recombinant human thrombopoietin

Intervention Type: DRUG

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

B1

Group Type: EXPERIMENTAL

Recombinant human thrombopoietin

Intervention Type: DRUG

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.

B2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.

C1-1

Group Type: EXPERIMENTAL

Recombinant human thrombopoietin

Intervention Type: DRUG

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.

C1-2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

C2-1

Group Type: EXPERIMENTAL

recombinant human thrombopoietin

Intervention Type: DRUG

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.

C2-2

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

C3-1

Group Type: EXPERIMENTAL

Recombinant human thrombopoietin

Intervention Type: DRUG

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.

C3-2

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

Interventions

Recombinant human thrombopoietin

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

Intervention Type: DRUG

Recombinant human thrombopoietin

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.

Intervention Type: DRUG

Placebo

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.

Intervention Type: DRUG

Recombinant human thrombopoietin

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.

Intervention Type: DRUG

Placebo

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

Intervention Type: DRUG

recombinant human thrombopoietin

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.

Intervention Type: DRUG

placebo

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

Intervention Type: DRUG

Recombinant human thrombopoietin

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.

Intervention Type: DRUG

placebo

Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C

Intervention Type: DRUG

Other Intervention Names

rhTPO; rhTPO; rhTPO; rhTPO; rhTPO

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenyang Sunshine Pharmaceutical Co., LTD.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

302 Military Hospital of China

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Quanrui WU, Master

Role: CONTACT

wuquanrui@3sbio.com

86 10 84892211

Sunqiong Cao, MD

Role: CONTACT

caosunqiong@3sbio.com

86 10 84892211

Facility Contacts

Jinhua Hu, MD

Role: primary

Haibin Su, MD

Role: backup

suhaibin302@163.com

Other Identifiers

3SBio-TPO-106

Identifier Type: -

Identifier Source: org_study_id