Phase III Study on HMPL-523 for Treatment of ITP

Primary Immune Thrombocytopenia (ITP) Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HMPL-523 in Treatment of Primary Immune Thrombocytopenia (ITP) in Adults(ESLIM-01 Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05029635
• Other study ID #: 2020-523-00CH1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 27, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: February 2023
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 188
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Primary Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

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

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital of Capital Medical University	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	People's Hospital of Peking University	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Heping Hospital Affiliated to Changzhi Medical College	Changzhi	Shanxi
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Southern Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhejiang Provincial Hospital of Chinese Medicine	Hangzhou	Zejiang Province
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affiliated hospital of USTC	Hefei	Anhui
China	The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University	Huai'an	Nanjing Province
China	Jinan Central Hospital Affilated to Sandong University	Jinan	Shandong
China	The second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	LiaoCheng People's Hospital	Liaocheng	Shandong
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital Of GuangXi Medical University	Nanning	GuangXi Province
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Jinshan Hospital Affiliated To Fudan University	Shanghai	Shanghai
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The Second People's Hospital Of Shenzhen	Shenzhen	Guangdong
China	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The second hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Affiliated Hospital of North China University of Technology	Tangshan	Hebei
China	Blood Institute of the Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	The First Affilicated Hospital of Xinjiang Medical University	Ürümqi	The Xinjiang Uygur Autonomous Region
China	Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Shanxi Provincial People's Hospital	Xi'an	Shanxi
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	Qinghai province people's hospital	Xining	Qinghai
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the durable response rate in the primary study	Platelet count =50×10^9 /L on at least 4 of 6 scheduled visits of Week14-Week24 in the primary study	treatment period Week14-Week24
Secondary	the overall response rate in the primary study	At least one platelet count =50×10^9 /L (except that induced by the rescue therapy) in the 24-week double-blind treatment period	treatment period Week1-Week24 in the primary study
Secondary	Incidence of treatment emergent adverse events	Adverse events classified according to NCI CTCAE version 5.0	treatment period Week1-Week24 in the primary study
Secondary	Plasma concentration at steady state 2 hours post dose (C2h,ss)	Plasma concentration of HMPL-523 and its main metabolites at steady state 2 hours post dose (C2h,ss) will be determined.	treatment period Week1-Week24 in the primary study
Secondary	Plasma concentration at steady state 2 hours post dose (C4h,ss)	Plasma concentration of HMPL-523 and its main metabolites at steady state 4 hours post dose (C4h,ss) will be determined.	treatment period Week1-Week24 in the primary study
Secondary	Plasma concentration at steady-state trough concentration (Cmin,ss)	Plasma concentration of HMPL-523 and its main metabolites at steady-state trough concentration (Cmin,ss) will be determined.	treatment period Week1-Week24 in the primary study