The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients

NCT03951623 | Completed Phase 1 DMC

• 1 other identifier: 2018-523-00CH1
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double blinded, placebo-controlled phase Ib clinical trial in adult patients with immune thrombocytopenia. Cross-over treatment will be allowed during the study.

Conditions

Immune Thrombocytopenia (ITP)

Keywords

syk inhibitor; ITP

Outcome Measures

Primary Outcomes (1)

• Number of Participants with any Adverse Event

  Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  From first dose to within 28 days after the last dose

Secondary Outcomes (3)

• Maximum plasma concentration (Cmax)

  Day 15, 16, 29, 43 and 47

• Area under the concentration-time curve in a selected time interval (AUC0-t)

  Day 15, 16, 29, 43 and 47

• Rate of Clinical Remission

  Day 1 to 8 weeks treatment

Study Arms (2)

treatment arm

ACTIVE COMPARATOR

Eligible subjects will be treated with planned dose of 100 mg, 200 mg and 300 mg HMPL-523 once daily for 8 weeks and 16 weeks open-label treatment.

Drug: HMPL-523

placebo arm

PLACEBO COMPARATOR

Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.

Drug: HMPL-523; Drug: Placebo

Interventions

HMPL-523 DRUG

HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

placebo arm; treatment arm

Placebo DRUG

HMPL-523 matching placebo will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

placebo arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• \~75 years old male of female
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Diagnosed immune thrombocytopenia before randomization with platelet decrease for more than 6 months.
• Patients with refractory or relapsed ITP who have been treated with 1st line anti-ITP regimen or have experienced splenectomy.
• Relative stable disease with World Health Organization (WHO) bleeding score of 0-1 and no rescue treatment needed within 2 weeks based on investigator's judgment.
• Laboratory tests meet the following conditions：
• During screening stage, twice PLT\<30x10\^9/L(exceed 24 hours)
• Hb≥90g/L(if iron-deficiency anemia,Hb\>80g/L),WBC\>2.5x10\^9/L, NEU\>1.8x10\^9/L
• Crea≤1.5xULN and CCR≥50mL/min
• TBIL、ALT、AST≤1.5xULN
• Amylase、lipase\<ULN
• INR、APTT\<20%xULN

You may not qualify if:

• Patients with secondary thrombocytopenia or patients have other auto immune diseases who need long term steroids or immunosuppressants treatment.
• Patients with Myelofibrosis, Myelodysplastic syndrome, Aplastic anemia, or other hematologic malignancies.
• Have splenectomy within 12 weeks before randomization
• Major surgery was performed within 4 weeks before randomization;Or require major elective surgery during the study period.
• Have malignant tumor(except basal cell carcinoma of skin and carcinoma in situ of cervix)
• Have previous/significant arterial/venous embolic disease
• History of serious cardiovascular disease, or QTc≥450 ms.
• Patients with resistant hypertension (Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg)
• Has a history of severe gastrointestinal diseases, such as dysphagia, active gastric ulcer, and is unable to take oral medication or has absorption disorder
• HIV infection
• Uncontrolled, active infections
• Known history of clinically significant liver disease, such as hepatitis b（HBV DNA ≥2000IU/mL (or ≥1×104 copies)）, hepatitis c, or cirrhosis
• Prior anti-ITP emergency treatment within 2 weeks before randomization.
• Prior anti-ITP treatment within 4 weeks before randomization except for stable dose steroids, including but not limited to Thrombopoietin, thrombopoietin receptor agonist, azathioprine, cyclosporine A and mycophenolate mofetil.
• Any condition requiring anti-coagulant therapy or the regular use of any medication having effluence to Platelet function.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Blood diseases hospital, Chinese academy of medical university

Tianjin, Tianjin Municipality, 300000, China

Location

Related Publications (1)

• Liu X, Zhou H, Hu Y, Yin J, Li J, Chen W, Huang R, Gong Y, Luo C, Mei H, Ding B, Gu C, Sun H, Leng Y, Ji D, Li Y, Yin H, Shi H, Chen K, Wang J, Fan S, Su W, Yang R. Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study. Lancet Haematol. 2023 Jun;10(6):e406-e418. doi: 10.1016/S2352-3026(23)00034-0. Epub 2023 Apr 4.

  PMID: 37028433 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Hongyan Yin

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 15, 2019
• Study Start: August 12, 2019
• Primary Completion: October 30, 2021
• Study Completion: July 31, 2022
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)