Phase III Study on HMPL-523 for Treatment of ITP
- Conditions
- Primary Immune Thrombocytopenia (ITP)
- Interventions
- Drug: Placebo
- Registration Number
- NCT05029635
- Lead Sponsor
- Hutchison Medipharma Limited
- 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)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 272
-
Voluntary signature of written informed consent form;
-
Male or female aged 18~75 years;
-
Performance Status score [Eastern Cooperative Oncology Group (ECOG) score] 0~1;
-
Having been diagnosed as ITP prior to randomization, and duration of disease is more than 6 months;
-
Intolerance or insufficient response, or recurrence after at least one anti-ITP standard drug therapy;
-
Patients must have a history of response to previous ITP therapy;
-
One combined anti-ITP therapy is allowed in this study, however, the following criteria need to be met:
- The dose of glucocorticoid has been stable for 4 weeks prior to randomization (<20 mg Prednisone equivalent);
- The dose of Danazol has been stable for 3 months prior to randomization;
- The dose of immunosuppressant (only including Azathioprine, Ciclosporin A, Mycophenolate mofetil) has been stable for 3 months prior to randomization.
-
The condition is relatively stable; WHO bleeding scale grade is 0-1; no emergency treatment is expected within 2 weeks as judged by investigators.
-
The laboratory examinations need to meet the following conditions (no treatment for this abnormal variable is given within one week prior to blood collection):
- 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;
- Hemoglobin ≥100 g/L, neutrophil count >1.5×10^9/L;
- Total bilirubin (TBIL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×upper limit of normal (ULN);
- Serum creatinine concentration ≤1.5×ULN and creatinine clearance ≥50 mL/min;
- Serum amylase and lipase ≤1.5×ULN;
- International normalized ratio (INR), activated partial thromboplastin time (APTT) not exceeding 20% of normal range.
-
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.
- Evidence on the presence of secondary causes of immune thrombocytopenia;
- Clinically serious hemorrhage requiring immediate adjustment of platelet (e.g., hypermenorrhea with significantly decreased hemoglobin);
- 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);
- known history of vital organ transplantation or hematopoietic stem cell / bone marrow transplantation;
- Has received live vaccine within 8 weeks prior to Day 1 (baseline visit); or plan for immunization with live vaccine during the study;
- Splenectomy within 12 weeks prior to randomization;
- Major surgery within 4 weeks prior to the randomization, or plan for major elective surgery during the study;
- Previous history of malignant tumors (except for the basal cell carcinoma of skin or cervical carcinoma in situ that have been cured);
- History of important arterial / venous embolic disease;
- Intracranial hemorrhage within 6 months before screening visit;
- 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);
- Hypertension that can not be controlled with drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
- Previous history of serious gastrointestinal disease, such as dysphagia, active gastric ulcer, inability to take drugs orally or absorption disorder for oral drugs;
- 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;
- 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);
- 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;
- Having received Rituximab within 14 weeks prior to randomization;
- Having received traditional Chinese medicine within 1 week prior to randomization;
- 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;
- 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);
- 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);
- Having received spleen tyrosine kinase Syk inhibitor (e.g., Fostamatinib) previously;
- Known allergy to the active ingredient or excipient of study drug;
- Presence of serious psychological or mental disorder;
- Alcoholic or drug abuser;
- Female patients in pregnancy or breast feeding;
- Being unsuitable to participate in this study, as considered by investigators.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo arm Placebo Drug: Placebo HMPL-523 matching placebo will be oral administrated once daily for 24 weeks. treatment arm HMPL-523 Eligible subjects will be treated with planned dose of 300 mg HMPL-523 once daily for 24 weeks
- Primary Outcome Measures
Name Time Method the durable response rate in the primary study treatment period Week14-Week24 Platelet count ≥50×10\^9 /L on at least 4 of 6 scheduled visits of Week14-Week24 in the primary study
- Secondary Outcome Measures
Name Time Method Incidence of treatment emergent adverse events treatment period Week1-Week24 in the primary study Adverse events classified according to NCI CTCAE version 5.0
the overall response rate in the primary study treatment period Week1-Week24 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
Plasma concentration at steady state 2 hours post dose (C2h,ss) treatment period Week1-Week24 in the primary study Plasma concentration of HMPL-523 and its main metabolites at steady state 2 hours post dose (C2h,ss) will be determined.
Plasma concentration at steady-state trough concentration (Cmin,ss) treatment period Week1-Week24 in the primary study Plasma concentration of HMPL-523 and its main metabolites at steady-state trough concentration (Cmin,ss) will be determined.
Plasma concentration at steady state 2 hours post dose (C4h,ss) treatment period Week1-Week24 in the primary study Plasma concentration of HMPL-523 and its main metabolites at steady state 4 hours post dose (C4h,ss) will be determined.
Trial Locations
- Locations (37)
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Chaoyang Hospital of Capital Medical University
🇨🇳Beijing, Beijing, China
The First Affiliated hospital of USTC
🇨🇳Hefei, Anhui, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
People's Hospital of Peking University
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
Southern Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital Of GuangXi Medical University
🇨🇳Nanning, GuangXi Province, China
The First Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Affiliated Hospital of North China University of Technology
🇨🇳Tangshan, Hebei, China
The Second People's Hospital Of Shenzhen
🇨🇳Shenzhen, Guangdong, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, 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
Heping Hospital Affiliated to Changzhi Medical College
🇨🇳Changzhi, Shanxi, 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, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, 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
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
The second Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Zhejiang Provincial Hospital of Chinese Medicine
🇨🇳Hangzhou, Zejiang Province, China