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

NCT03673215 | Unknown Early Phase 1

• 1 other identifier: 3SBio-TPO-106
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (11)

• 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.).

  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 \[0-24\]).

  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 \[0-t\]).

  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 \[0-∞\]).

  For 9 days

• Cmax of rhTPO

  To assess plasma rhTPO PK Parameter：Observed maximum plasma concentration(Cmax).

  For 9 days

• tmax of rhTPO

  To assess plasma rhTPO PK Parameter：Time to Cmax (tmax).

  For 9 days

• t1/2 of rhTPO

  To assess plasma rhTPO PK Parameter：Elimination half-life (t1/2).

  For 9 days

• MRT for rhTPO

  To assess plasma rhTPO PK Parameter：Mean residence time (MRT).

  For 9 days

• Kel of rhTPO

  To assess plasma rhTPO PK Parameter：Elimination rate constant （Kel）.

  For 9 days

• Vd of rhTPO

  To assess plasma rhTPO PK Parameter：Apparent volume of distribution（Vd）.

  For 9 days

• CL/F of rhTPO

  To assess plasma rhTPO PK Parameter：apparent clearance (CL/F).

  For 9 days

Secondary Outcomes (2)

• Immunogenicity of rhTPO

  Up to 12 months

• Change of Platelet count (PLT)

  Up to 29 days

Study Arms (9)

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

Interventions

Recombinant human thrombopoietin 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

Also known as: rhTPO

A

placebo DRUG

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

B2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients with cirrhosis caused by chronic liver disease who have been diagnosed by biopsy/imaging (Child-Pugh class A, B, and C).
• \. Life expectancy≥3 months.
• \. Platelet count≤80×109/ L.
• \. 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.
• \. Voluntary written informed consent.

You may not qualify if:

• Subjects allergic to any component of investigational drug.
• Subjects with cirrhosis caused by drug-induced liver injury.
• Subjects with history of splenectomy or liver transplantation.
• Liver cirrhosis with serious complications, including: hepatic encephalopathy, intractable ascites, upper gastrointestinal bleeding, etc.
• Subjects with Liver failure.
• 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.
• 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.
• 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.;
• Subjects with diseases with higher bleeding risk, such as coagulation factor deficiency or Vascular pseudohemophilia factor deficiency.
• Subjects with severe infections that are not effectively controlled.
• 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.
• Subjects who had undergone trans jugular intrahepatic portal shunt (TIPS);
• Subjects with Anti-HIV positive antibodies or Anti- TPHA positive antibodies.
• Subjects who received any therapy with increased platelet count within the 3 weeks or platelet transfusion within 2 weeks before randomization.
• No more than 30 days or 5 half-lives after investigational drug treatment for other studies (whichever is longer).

Sponsors & Collaborators

• Shenyang Sunshine Pharmaceutical Co., LTD.: lead

Study Sites (1)

302 Military Hospital of China

Beijing, Beijing Municipality, 100039, China

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Thrombopoietin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Quanrui WU, Master

CONTACT

86 10 84892211; wuquanrui@3sbio.com

Sunqiong Cao, MD

CONTACT

86 10 84892211; caosunqiong@3sbio.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: September 17, 2018
• Study Start: June 28, 2018
• Primary Completion: October 8, 2020
• Study Completion: December 31, 2020
• Last Updated: March 23, 2020

Record last verified: 2020-03

Locations

CN (1)