Clinical trial NCT05029635: Phase III Study on HMPL-523 for Treatment of ITP
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia (ITP)
Keywords: HMPL-523, sovleplenib, ITP
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2021-08-31
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: the durable response rate in the primary study
timeFrame: treatment period Week14-Week24
Secondary outcomes:
measure: the overall response rate in the primary study
timeFrame: treatment period Week1-Week24 in the primary study
measure: Incidence of treatment emergent adverse events
timeFrame: treatment period Week1-Week24 in the primary study
measure: Plasma concentration at steady state 2 hours post dose (C2h,ss)
timeFrame: treatment period Week1-Week24 in the primary study
measure: Plasma concentration at steady state 2 hours post dose (C4h,ss)
timeFrame: treatment period Week1-Week24 in the primary study
measure: Plasma concentration at steady-state trough concentration (Cmin,ss)
timeFrame: treatment period Week1-Week24 in the primary study
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated hospital of USTC
state: Anhui
city: Beijing
country: China
facility: Beijing Chaoyang Hospital of Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: People's Hospital of Peking University
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Southern Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The Second People's Hospital Of Shenzhen
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital Of GuangXi Medical University
state: GuangXi Province
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Affiliated Hospital of North China University of Technology
state: Hebei
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Huai'an
country: China
facility: The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University
state: Nanjing Province
city: Xining
country: China
facility: Qinghai province people's hospital
state: Qinghai
city: Jinan
country: China
facility: Jinan Central Hospital Affilated to Sandong University
state: Shandong
city: Liaocheng
country: China
facility: LiaoCheng People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Jinshan Hospital Affiliated To Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Taiyuan
country: China
facility: The second hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Ürümqi
country: China
facility: The First Affilicated Hospital of Xinjiang Medical University
state: The Xinjiang Uygur Autonomous Region
city: Tianjin
country: China
facility: Blood Institute of the Chinese Academy of Medical Sciences
state: Tianjin
city: Kunming
country: China
facility: The second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Provincial Hospital of Chinese Medicine
state: Zejiang Province
Study officials:
affiliation: offices director
name: Renchi Yang, professor
role: PRINCIPAL_INVESTIGATOR
References: