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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
58

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100039
        • Recruiting
        • 302 Military Hospital of China
        • Contact:
          • Jinhua Hu, MD
        • Contact:
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: A
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 A
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
EXPERIMENTAL: B1
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 A
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
PLACEBO_COMPARATOR: B2
Drug: Placebo
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
Drug: Placebo
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
EXPERIMENTAL: C1-1
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 A
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
PLACEBO_COMPARATOR: C1-2
Drug: Placebo
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class B.
Drug: Placebo
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
EXPERIMENTAL: C2-1
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.
Other Names:
  • rhTPO
PLACEBO_COMPARATOR: C2-2
Drug: placebo
Placebo will be administered single dose subcutaneous injection in the patients with liver function impairment classified as Child-Pugh class C
EXPERIMENTAL: C3-1
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 A
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
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.
Other Names:
  • rhTPO
PLACEBO_COMPARATOR: C3-2
Drug: placebo
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shenyang Sunshine Pharmaceutical Co., LTD.

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 28, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 8, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 17, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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