Multicentre, Randomised Phase III Study of the Efficacy and Safety of Hetrombopag Olamine in Idiopathic Thrombocytopenic Purpura (ITP) Patient

A Phase III,Multicentre, Randomized, Double-Blind and Open-Label Study to Evaluate the Safety and Efficacy of Hetrombopag Olamine in Patients With Idiopathic Thrombocytopenic Purpura

A multicentre, randomised, double-blind,4-stages phase III study enrolled 414 patients with chronic, previously treated ITP. Dosage could be adjusted (2.5~.75 mg/day) to maintain platelet counts 50~250×109/L

Study Overview

• Status: Completed
• Conditions: Idiopathic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Hetrombopag Olamine; Drug: matching placebo

• Study Type: Interventional
• Enrollment (Actual): 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital,Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300041
      • Hospital of Blood Diseases, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed diagnosis of ITP ≥6 months;Platelets <30×109/L.
2. No evidence of other causes of thrombocytopenia.
3. Subjects who are refractory or have relapsed after at least one prior ITP therapy.
4. Previous therapy for ITP including rescue must have been completed at least 2 weeks prior to randomization.
5. Subjects treated with maintenance immunosuppressive therapy must be receiving a dose that has been stable for at least 1 month.
6. PT result no exceed normal by more than ±3s,APTT result no exceed normal by more than ±10s.
7. Signed informed consent.

Exclusion Criteria:

1. Patients with any prior history of arterial or venous thrombosis，or diagnosis as Thrombophilia.
2. Subjects diagnosed with tumor.
3. Have pre-existing cardiac disease within the last 3 months.No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) >450msec or QTc >480 for patients with a Bundle Branch Block.
4. Female subjects who are nursing or pregnant at screening or pre-dose on baseline.
5. Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist within 30 days .
6. Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks of the study start and until the end of the study.
7. Any laboratory or clinical evidence for HIV infection.Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening.
8. ALT> 1.5 x upper limit of normal (ULN), AST> 3 x upper limit of normal (ULN)) DBLI> 1.2 x upper limit of normal (ULN),Scr> 1.2 x upper limit of normal (ULN)
9. The subject has participated in other clinical trial within the 3 months prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1; oral hetrombopag at an initial dose of 2.5 mg once daily	Drug: Hetrombopag Olamine; once daily
EXPERIMENTAL: Arm 2; oral hetrombopag at an initial dose of 5 mg once daily	Drug: Hetrombopag Olamine; once daily
PLACEBO_COMPARATOR: Arm 3; oral placebo at an initial dose of 2.5 mg once daily	Drug: matching placebo; once daily
PLACEBO_COMPARATOR: Arm 4; oral placebo at an initial dose of 5 mg once daily	Drug: matching placebo; once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the proportion of patients with a platelet count ≥50×109/L after Day 57.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, Hou M, Yao Y, Liu L, Wang Y, Wu D, Zhang L, Zheng C, Shen X, Hu Q, Liu J, Jin J, Luo J, Zeng Y, Gao S, Zhang X, Zhou X, Shi Q, Xia R, Xie X, Jiang Z, Gao L, Bai Y, Li Y, Xiong J, Li R, Zou J, Niu T, Yang R, Hu Y. Dose tapering to withdrawal stage and long-term efficacy and safety of hetrombopag for the treatment of immune thrombocytopenia: Results from an open-label extension study. J Thromb Haemost. 2022 Mar;20(3):716-728. doi: 10.1111/jth.15602. Epub 2021 Dec 15.
• Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, Hou M, Yao Y, Liu L, Wang Y, Wu D, Zhang L, Zheng C, Shen X, Hu Q, Liu J, Jin J, Luo J, Zeng Y, Gao S, Zhang X, Zhou X, Shi Q, Xia R, Xie X, Jiang Z, Gao L, Bai Y, Li Y, Xiong J, Li R, Zou J, Niu T, Yang R, Hu Y. A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2017
• Primary Completion (ACTUAL): November 11, 2019
• Study Completion (ACTUAL): January 7, 2021

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (ACTUAL): July 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: ITP
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: HR-TPO-III-ITP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No