Herombopag + rhTPO in Severe Immune Thrombocytopenia

Evaluating the Efficacy and Safety of the Combination of Herombopag and Human Thrombopoietin (rhTPO) in the Treatment of Patients With Severe Immune Thrombocytopenia (ITP)

Severe immune thrombocytopenia (ITP) is a life-threatening acquired hemorrhagic disease with dramatically decreased platelet number and clinical bleeding symptoms. Some patients with severe ITP did not respond to first-line treatment including steroids and IVIG. It was critical for them to use effective treatments to promote platelet and reduce the risk of fatal bleeding. In this study, the patients with severe ITP will be treated with hetrombopag, rhTPO, and the combination of hetrombopag and rhTPO, respectively. The effect evaluation includes the increase of platelet number and decrease of bleeding scores. Changes of coagulation, platelet activation, fribrinolysis influence, and thrombotic events will also be accessed for the safety of treatments. The aim of this study is to demonstrate that the combination of hetrombopag and rhTPO for severe ITP is more effective than the other two monotherapy and does not increase thrombotic events or thrombosis risk.

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: rhTPO; Drug: Herombopag

Detailed Description

Patients with severe ITP will be randomly assigned to three groups: rhTPO group, Herombopag Group, Herombopag combined with rhTPO group. The effective rate of treatment, the rate and amplitude of platelet increase, the response time of platelet maintenance, and the effect of combination therapy on hemostasis will be compared. At the same time, the investigators will analyze the markers of thrombosis and thrombotic events to assess the safety of combination therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hong Tian; Phone Number: 15850150032; Email: tianhong0718@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • Recruiting
      • Jie Yin
      • Contact: Jie Yin, MD.，PhD; Phone Number: +86-512-67781521; Email: yinjie@suda.edu.cn

Participation Criteria

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. Male or female,70 ≥age≥18；
2. Diagnosed as primary immune thrombocytopenia；
3. Platelet count was less than 10 × 10E9 / L with active bleeding, or bleeding score ≥ 5 points；
4. No use of IVIG, Avatrombopag, Eltrombopag or Romiplostim 2 weeks before treatment；
5. Rituximab was used for at least 2 months, and other immunosuppressants were stable for at least 4 weeks.
6. There was no history of platelet transfusion one week before treatment.

Exclusion Criteria:

1. Secondary thrombocytopenia caused by other autoimmune diseases and virus infection was excluded；
2. Patients with active malignant tumors, pregnancy, severe cardiovascular， cerebrovascular diseases and a history of arteriovenous thrombotic diseases were excluded；
3. Patients deemed unsuitable for enrollment by the investigator；
4. Patients with thrombotic disease or serious uncontrolled cardiovascular and cerebrovascular disease;
5. Patients reject to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhTPO; rhTPO will be injected subcutaneously at 300 u/kg daily for 14 days.	Drug: rhTPO; subcutaneous injection
Experimental: Herombopag; Herombopag will be taken orally at 5 mg daily for 28 days.	Drug: Herombopag; Orally by mouth
Experimental: Herombopag in combination of rhTPO; Herombopag will be taken orally at 5 mg daily for 28 days，while rhTPO will be injected subcutaneously at 300 u/kg daily for 14 days	Drug: rhTPO; subcutaneous injection; Drug: Herombopag; Orally by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	platelets ≥30*10E9/L, and at least 2 times higher than the baseline platelet count, and there is no hemorrhagic manifestations	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment
The rate and magnitude of the increase in platelet count	The rate and magnitude of the increase in platelet count after treatment	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment
Platelet maintenance response time	Platelets stay above 30*10E9/L	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet fuction	Platelet aggregation function assay and the expression of P selectin on platelet surface	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment
the markers of thrombosis and fibrinolysis	platelet-derived microparticals in plasma, concentration of Plasminogen Activator Inhibitor-1 （PAI-1）, D-D dimer, tissue plasminogen activator （tPA），urokinase-type plasminogen activator （uPA） and Thrombin activatable fibrinolysis inhibitor （TAFI）	From randomization to 28 days after rhTPO/Herombopag/Herombopag+rhTPO treatment
Thrombotic events	the number/time/site of thrombotic events （lower extremity deep vein thrombosis, pulmonary embolism, intracranial thrombosis, .etc）in participants	From randomization to 3 months after rhTPO/Herombopag/Herombopag+rhTPO treatment

Collaborators and Investigators

• Sponsor: Yin Jie
• Investigators: Principal Investigator: Jie Yin, First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): November 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: severe; immune thrombocytopenia; Herombopag; recombinant human thrombopoietin
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: SZ-ITP01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No