Phase III Study on HMPL-523 for Treatment of ITP

NCT ID: NCT05029635

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-27
• Study Completion Date: 2025-05-30

Brief Summary

The purpose of this study is to determine whether HMPL-523 (sovleplenib) is safe and effective in the treatment of chronic Immune Thrombocytopenic Purpura (ITP).

Detailed Description

This is a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with primary immune thrombocytopenia to determine whether HMPL-523 (sovleplenib) is safe and effective in the treatment of chronic Immune Thrombocytopenic Purpura (ITP)

Conditions

Primary Immune Thrombocytopenia (ITP)

Study Design

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

Study Groups

treatment arm

Eligible subjects will be treated with planned dose of 300 mg HMPL-523 once daily for 24 weeks

Group Type: ACTIVE_COMPARATOR

HMPL-523

Intervention Type: DRUG

HMPL-523 will be oral administrated once daily for 24 weeks

placebo arm

Drug: Placebo HMPL-523 matching placebo will be oral administrated once daily for 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

HMPL-523 matching placebo will be oral administrated once daily for 24 weeks .

Interventions

HMPL-523

HMPL-523 will be oral administrated once daily for 24 weeks

Intervention Type: DRUG

Placebo

HMPL-523 matching placebo will be oral administrated once daily for 24 weeks .

Intervention Type: DRUG

Other Intervention Names

Sovleplenib

Eligibility Criteria

Inclusion Criteria

1. Voluntary signature of written informed consent form;

2. Male or female aged 18~75 years;

3. Performance Status score [Eastern Cooperative Oncology Group (ECOG) score] 0~1;

4. Having been diagnosed as ITP prior to randomization, and duration of disease is more than 6 months;

5. Intolerance or insufficient response, or recurrence after at least one anti-ITP standard drug therapy;

6. Patients must have a history of response to previous ITP therapy;

7. One combined anti-ITP therapy is allowed in this study, however, the following criteria need to be met:

1. The dose of glucocorticoid has been stable for 4 weeks prior to randomization (<20 mg Prednisone equivalent);

2. The dose of Danazol has been stable for 3 months prior to randomization;

3. The dose of immunosuppressant (only including Azathioprine, Ciclosporin A, Mycophenolate mofetil) has been stable for 3 months prior to randomization.

8. The condition is relatively stable; WHO bleeding scale grade is 0-1; no emergency treatment is expected within 2 weeks as judged by investigators.

9. The laboratory examinations need to meet the following conditions (no treatment for this abnormal variable is given within one week prior to blood collection):

1. Average platelet count <30×10^9 /L (and none > 35×10^9 /L unless as a result of rescue therapy) from at least 3 qualifying counts;

2. Hemoglobin ≥100 g/L, neutrophil count >1.5×10^9/L;

3. Total bilirubin (TBIL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×upper limit of normal (ULN);

4. Serum creatinine concentration ≤1.5×ULN and creatinine clearance ≥50 mL/min;

5. Serum amylase and lipase ≤1.5×ULN;

6. International normalized ratio (INR), activated partial thromboplastin time (APTT) not exceeding 20% of normal range.

10. Male or female patients of childbearing potential must agree to use effective contraceptive methods during the study and within 90 days after last dose of study drug, e.g., double barrier contraceptive method, condom, oral or injectable contraceptives, intrauterine device, etc. Postmenopausal women (>50 years old and no menses for >1 year) and surgically sterilized women are not subject to this condition.

Exclusion Criteria

1. Evidence on the presence of secondary causes of immune thrombocytopenia;

2. Clinically serious hemorrhage requiring immediate adjustment of platelet (e.g., hypermenorrhea with significantly decreased hemoglobin);

3. Clinically symptomatic gastrointestinal hemorrhage within 6 months prior to screening visit (e.g., haematemesis, tarry stool, however, the positive occult blood test without any sign or symptom of gastrointestinal hemorrhage will not be considered as "clinically symptomatic", or hemorrhoids hemorrhage is one exception);

4. known history of vital organ transplantation or hematopoietic stem cell / bone marrow transplantation;

5. Has received live vaccine within 8 weeks prior to Day 1 (baseline visit); or plan for immunization with live vaccine during the study;

6. Splenectomy within 12 weeks prior to randomization;

7. Major surgery within 4 weeks prior to the randomization, or plan for major elective surgery during the study;

8. Previous history of malignant tumors (except for the basal cell carcinoma of skin or cervical carcinoma in situ that have been cured);

9. History of important arterial / venous embolic disease;

10. Intracranial hemorrhage within 6 months before screening visit;

11. History of serious cardiovascular disease (e.g., grade III/IV congestive heart failure, arrhythmia or angina pectoris requiring drug therapy, unstable angina pectoris, intracoronary stent implantation, angioplasty or coronary artery bypass grafting, or QTc ≥450 ms);

12. Hypertension that can not be controlled with drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);

13. Previous history of serious gastrointestinal disease, such as dysphagia, active gastric ulcer, inability to take drugs orally or absorption disorder for oral drugs;

14. Human immunodeficiency virus (HIV) infection, or hepatitis B (in case of positive HBsAg or HBcAb, positive HBV DNA needs to be determined), or hepatitis C (positive HCV RNA), or liver cirrhosis;

15. Significant active infection that is not controlled clinically (e.g., sepsis, pneumonia or abscess), or serious infection within 6 weeks prior to randomization (leading to hospitalization or requiring treatment with antibiotic injections);

16. Has received rescue therapy for ITP within 2 weeks prior to randomization; Has received the treatment for the objective of increasing platelet within 4 weeks prior to randomization (including but not limited to glucocorticoid, thrombopoietin, thrombopoietin receptor agonist, Cyclosporine A, Mycophenolate mofetil, etc.), except those meeting the inclusion criterion 7;

17. Having received Rituximab within 14 weeks prior to randomization;

18. Having received traditional Chinese medicine within 1 week prior to randomization;

19. Requiring long-term/continuous use of the drugs that may affect platelet function [including but not limited to aspirin, Clopidogrel, ticagrelor, NSAIDs, etc.], or anticoagulants;

20. Intake of potent CYP3A inhibitor or inducer, as well as sensitive or narrow therapeutic window substrates of CYP3A, CYP1A2 or CYP2B6 two weeks (three weeks for Hypericum perforatum) or 5 half-lives prior to randomization (whichever is longer);

21. Having participated in the clinical study for drugs or invasive medical device 4 weeks prior to randomization (or within 5 half-lives of the study drug prior to randomization, whichever is longer);

22. Having received spleen tyrosine kinase Syk inhibitor (e.g., Fostamatinib) previously;

23. Known allergy to the active ingredient or excipient of study drug;

24. Presence of serious psychological or mental disorder;

25. Alcoholic or drug abuser;

26. Female patients in pregnancy or breast feeding;

27. Being unsuitable to participate in this study, as considered by investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renchi Yang, professor

Role: PRINCIPAL_INVESTIGATOR

offices director

Locations

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

The First Affiliated hospital of USTC

Hefei, Anhui, China

Beijing Chaoyang Hospital of Capital Medical University

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

People's Hospital of Peking University

Beijing, Beijing Municipality, China

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Lanzhou University Second Hospital

Lanzhou, Gansu, China

Guangdong General Hospital

Guangzhou, Guangdong, China

Southern Hospital of Southern Medical University

Guangzhou, Guangdong, China

The Second People's Hospital Of Shenzhen

Shenzhen, Guangdong, China

The First Affiliated Hospital Of GuangXi Medical University

Nanning, Guangxi, China

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Affiliated Hospital of North China University of Technology

Tangshan, Hebei, China

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Xiangyang Central Hospital

Xiangyang, Hubei, China

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Xiangya Hospital Central South University

Changsha, Hunan, China

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University

Huai'an, Nanjing Province, China

Qinghai province people's hospital

Xining, Qinghai, China

Jinan Central Hospital Affilated to Sandong University

Jinan, Shandong, China

LiaoCheng People's Hospital

Liaocheng, Shandong, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Jinshan Hospital Affiliated To Fudan University

Shanghai, Shanghai Municipality, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, Shanxi, China

The second hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Shanxi Provincial People's Hospital

Xi’an, Shanxi, China

West China Hospital，Sichuan University

Chengdu, Sichuan, China

The First Affilicated Hospital of Xinjiang Medical University

Ürümqi, The Xinjiang Uygur Autonomous Region, China

Blood Institute of the Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

The second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Zhejiang Provincial Hospital of Chinese Medicine

Hangzhou, Zejiang Province, China

Countries

China

References

Hu Y, Liu X, Zhou H, Wang S, Huang R, Wang Y, Du X, Sun J, Zhou Z, Yan Z, Chen W, Wang W, Liu Q, Zeng Q, Gong Y, Yin J, Shen X, Ye B, Chen Y, Xu Y, Sun H, Cheng Y, Liu Z, Wang C, Yuan G, Zhang X, Li X, Cheng P, Guo X, Jiang Z, Yang F, Yang L, Luo C, Xiao T, Fu S, Yin H, Guo X, Xu Q, Fan S, Shi MM, Su W, Mei H, Yang R. Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Haematol. 2024 Aug;11(8):e567-e579. doi: 10.1016/S2352-3026(24)00139-X. Epub 2024 Jun 14.

Reference Type: DERIVED

PMID: 38885672 (View on PubMed)

Other Identifiers

2020-523-00CH1

Identifier Type: -

Identifier Source: org_study_id