HMPL-523 (Sovleplenib) in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA)

A Randomized, Double-Blind, Placebo-Controlled Phase II/III Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HMPL-523 in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia

Phase II Study: To evaluate the safety and preliminary efficacy of HMPL-523 in adult patients with wAIHA.

Phase III Study(Part A): Confirmation of Efficacy safety and of HMPL-523 in adult patients with wAIHA.

Phase III Study (Part B): To further evaluate the long-term safety and tolerability of HMPL-523 in adult patients with wAIHA.

Study Overview

• Status: Active, not recruiting
• Conditions: Warm Antibody Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: HMPL-523(300mg PO QD); Drug: Placebo

Detailed Description

Phase II Study: An eight-week randomized, placebo-controlled, double-blind phase followed by at least a 16-week open-label HMPL-523 treatment to evaluate the safety and preliminary efficacy of HMPL-523. The primary endpoint was the proportion of patients with overall Hb response by week 24.

Phase III study (Part A):A 24-week randomized, placebo-controlled double-blind phase to evaluate efficacy and safety of HMPL-523. The primary endpoint was the proportion of patients who achieve a durable response during weeks 5 to 24.

Phase III Study (Part B): An open-label Phase evaluating long-term safety and efficacy of HMPL-523 treatment. Eligible patients include those with lack of efficacy during the 20-week Phase III Part A treatment, completion of the Phase II study, or completion of 24-week Phase III Part A treatment with investigators assessment of potential benefit from open-label treatment with HMPL-523.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking Union Medical College Hospital
  • Tianjin, China
    • Hematology Hospital of Chinese Academy of Medical Sciences
  • Anhui
    • Fuyang, Anhui, China
      • Fuyang Hospital Of Anhui Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital
    • Shenzhen, Guangdong, China
      • Shenzhen Second People's Hospital
    • Zhanjiang, Guangdong, China
      • Affiliated Hospital of Guangdong Medical University
  • Guangxi
    • Guilin, Guangxi, China
      • Guilin Medical College Affiliated Hospital
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital
  • Hebei
    • Baoding, Hebei, China
      • Affiliated Hospital of Hebei University
    • Chengde, Hebei, China
      • Affiliated Hospital of Chengde Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin First Hospital
  • Henan
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science and Technology
    • Xinxiang, Henan, China
      • Xinxiang Central Hospital
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Xiangyang, Hubei, China
      • Xiangyang Center Hospital
  • Hunan
    • Changde, Hunan, China
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China
      • The third xiangya hospital of Central South University
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University
    • Chenzhou, Hunan, China
      • Chenzhou First People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nantong, Jiangsu, China
      • Affiliated Hospital of Nantong University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China
      • The First affiliated hospital of nanchang uiversity
  • Jilin
    • Changchun, Jilin, China
      • Bethune First Hospital Of Jilin University
  • Qinghai Provincial
    • Xining, Qinghai Provincial, China
      • Qinghai provincial people's hospital
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Shaanxi Provincial People's Hospital
  • Shandong
    • Binzhou, Shandong, China
      • Affiliated Hospital of Binzhou Medical College
    • Yantai, Shandong, China
      • Yantai Yuhuangding Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Jinshan Hospital of Fudan University
  • Shanxi
    • Changzhi, Shanxi, China
      • Heping Hospital Affiliated to Changzhi Medical College
  • Sichuan
    • Luzhou, Sichuan, China
      • The Affiliated Hospital of Southwest Medical University
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • Xinjiang Uygur Autonomous Region People's Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • The Second Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of WMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily signed the informed consent form (ICF);
2. Males or females aged 18 to 75 years;
3. Patients diagnosed with primary wAIHA or secondary wAIHA whose underlying diseases are stable;
4. Organs in good function.

Exclusion Criteria:

1. Patients with other types of AIHA other than wAIHA;
2. Patients with secondary wAIHA with unstable underlying disease;
3. Patients with drug-induced secondary wAIHA;
4. Patients with infections requiring systemic treatment;
5. Patients previously treated with Syk inhibitors (e.g., fostamatinib);
6. Patients with known allergy to the active ingredients or excipients of the study drug;
7. Patients with serious psychological or mental disorder;
8. Alcoholic or drug abuser;
9. Female patients who are pregnant and lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HMPL-523; Phase II: Eligible subjects will receive 300 mg HMPL-523 treatment once daily for 8 weeks and at least 16 weeks open-label treatment. Phase III: Part A (Randomized, Double-Blind Phase): Eligible subjects will receive 300 mg HMPL-523 treatment once daily for 24 weeks. Part B (Open-label Phase): Eligible subjects will roll-over into the open-label phase and receive treatment with HMPL-523 at the same dose administered after 24-week randomized controlled trial phase (Part A) or in Phase II. Treatment will continue until 24 weeks after the last subject is enrolled in Part B.	Drug: HMPL-523(300mg PO QD); HMPL-523(300mg PO QD); Other Names: Sovleplenib
Placebo Comparator: Placebo; Phase II: Eligible subjects will receive 300 mg HMPL-523 matched placebo treatment once daily for 8 weeks. Phase III: Part A (Randomized, Double-Blind Phase): Eligible subjects will receive 300 mg HMPL-523 matched placebo treatment once daily for 24 weeks.	Drug: Placebo; Placebo(300mg PO QD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: Overall Hb response rate	Phase II: Overall Hb response rate: The proportion of patients with overall Hb response by Week 24	24Weeks
Phase III(Part A): Durable Hb response rate	Phase III(Part A):Durable Hb response rate: The proportion of patients who achieve a durable response by Week 24 during Part A	24Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: Overall Hb response rate	Phase II: Overall Hb response rate: the proportion of patients with overall Hb response by Week 8	8 Weeks
Phase II: Durable Hb response rate	Phase II: Durable Hb response rate: the proportion of patients who achieve a durable response by Week 24.	24 Weeks
Phase II: Median change in Hb	Phase II: Median change from baseline in Hb at Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Effects on reticulocyte count	Phase II: Change from baseline in reticulocyte count at Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Effects on lactate dehydrogenase	Phase II: Change from baseline in lactate dehydrogenase(LDH) at Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Effects on haptoglobin	Phase II: Change from baseline in haptoglobin at Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Effects on total bilirubin(TBIL)	Phase II: Change from baseline in total bilirubin(TBIL) at Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Proportion of rescue therapy	Phase II: Proportion of patients who received rescue therapy by Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Proportion of patients with dose reduction in baseline anti-wAIHA medications	Phase II: Proportion of patients who had a dose reduction in glucocorticoids or other baseline concomitant anti-wAIHA medications by Weeks 8 and 24 of treatment.	24 Weeks
Phase II: Time to response	Phase II: Time to response	24 Weeks
Phase II: Effect of study treatment on patient fatigue	Phase II: Evaluation of the effect of study treatment on fatigue at Weeks 8 and 24, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)	24 Weeks
Phase II: Effect of study treatment on quality of life	Phase II: Evaluation of the effect of study treatment on quality of life at Weeks 8 and 24, as assessed by the 36-Item Short Form Health Survey (SF-36).	24 Weeks
Phase III(Part A): Overall Hb response rate	Phase III(Part A): Proportion of patients who achieved an overall Hb response during the 20-week and 24-week double-blind treatment periods(defined as at least one Hb value ≥100g/L with an increase of at least 20g/L from baseline, not attributable to rescue therapy).	24 Weeks
Phase III(Part A): Median change in Hb	Phase III(Part A): Median change from baseline in Hb during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Effects on reticulocyte count	Phase III(Part A): Change from baseline in reticulocyte count during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Effects on lactate dehydrogenase	Phase III(Part A): Change from baseline in lactate dehydrogenase(LDH) during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Effects on haptoglobin	Phase III(Part A): Change from baseline in haptoglobin during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Effects on total bilirubin(TBIL)	Phase III(Part A): Change from baseline in total bilirubin(TBIL) during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Proportion of rescue therapy	Phase III(Part A): Proportion of patients who received protocol-defined rescue therapy during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III (Part A): Proportion of patients reducing or discontinuing baseline anti-wAIHA medications	Phase III(Part A):The proportion of patients who reduced or discontinued glucocorticoids or other baseline concomitant anti-wAIHA medications during the 20-week and 24-week double-blind treatment periods.	24 Weeks
Phase III(Part A): Time to first response	Phase III(Part A): Time to first response	24 Weeks
Phase III(Part A): Duration of durable response	Phase III(Part A): Duration of durable response	24 Weeks
Phase III(Part A): Cumulative duration of response	Phase III(Part A): Cumulative duration of response	24 Weeks
Phase III(Part A): Effect of study treatment on patient fatigue	Phase III(Part A): Effect of study treatment on patient fatigue during the 20-week and 24-week treatment periods, as assessed by the FACIT-F score (40 items; range, 0-160), including the FACIT-Fatigue subscale (13 items; range, 0-52).	24 Weeks
Phase III(Part A): Effect of study treatment on patients' quality	Phase III(Part A): Effect of study treatment on patients' quality of life during the 20-week and 24-week treatment periods, as assessed by SF-36.	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAEs)	Incidence of treatment-emergent adverse events (TEAEs) assessed according to NCI CTCAE Version 5.0.	36 Months
Phase II:Efficacy in patients with DAT positivity confirmed by the central laboratory	Phase II: Assessed by overall Hb response rate and durable response rate.	24 Weeks
Phase III(Part B): Durable Hb response rate	Phase III(Part B): Durable Hb response rate: the proportion of patients who achieve a durable response during Part B.	30 Months

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Fengkui Zhang, professor, offices director

Publications and helpful links

General Publications

• Zhao X, Sun J, Zhang Z, Chen M, Gong T, He G, Li Y, Liu H, Li F, Li X, Zhou H, Wang X, Hong M, Lei L, Yin H, Luo X, Li Y, Fan S, Guo X, Shi MM, Su W, Zhang L, Han B, Zhang F. Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study. Lancet Haematol. 2025 Feb;12(2):e97-e108. doi: 10.1016/S2352-3026(24)00344-2. Epub 2025 Jan 9.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Actual): November 25, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: 2022-523-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The results of this study can be published in core journals or international scientific conferences, and the primary investigators who make significant contributions to the implementation and management of this study and the personnel who makes great contributions to the design, interpretation or analysis of this study (such as the staffs or consultants of the sponsor) can have their authorship attribution. The sponsor promises to provide the manuscript to the investigator for review before publication of any result of the study. Investigators have to obtain the approval of the sponsor before submitting academic articles or abstracts. The study personnel have the right to publish results of this study, however, the requirement of protecting confidential information must be met.

The confidential information is the property of the sponsor only, cannot be disclosed to others without the written approval of the sponsor, and cannot be used for other purposes.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No