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

NCT ID: NCT03951623

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-12
• Study Completion Date: 2022-07-31

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.

Detailed Description

Approximate 51 to 60 patients will be enrolled in dose escalation (3 cohorts, 8-20 subjects each with the ratio of 3:1 vs Placebo) .

Conditions

Immune Thrombocytopenia (ITP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

treatment arm

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.

Group Type: ACTIVE_COMPARATOR

HMPL-523

Intervention Type: DRUG

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

placebo arm

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

Group Type: PLACEBO_COMPARATOR

HMPL-523

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

HMPL-523

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent form

2. 18~75 years old male of female

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Diagnosed immune thrombocytopenia before randomization with platelet decrease for more than 6 months.

5. Patients with refractory or relapsed ITP who have been treated with 1st line anti-ITP regimen or have experienced splenectomy.

6. 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.

7. 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

Exclusion Criteria

1. Patients with secondary thrombocytopenia or patients have other auto immune diseases who need long term steroids or immunosuppressants treatment.

2. Patients with Myelofibrosis, Myelodysplastic syndrome, Aplastic anemia, or other hematologic malignancies.

3. Have splenectomy within 12 weeks before randomization

4. Major surgery was performed within 4 weeks before randomization;Or require major elective surgery during the study period.

5. Have malignant tumor(except basal cell carcinoma of skin and carcinoma in situ of cervix)

6. Have previous/significant arterial/venous embolic disease

7. History of serious cardiovascular disease, or QTc≥450 ms.

8. Patients with resistant hypertension (Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg)

9. Has a history of severe gastrointestinal diseases, such as dysphagia, active gastric ulcer, and is unable to take oral medication or has absorption disorder

10. HIV infection

11. Uncontrolled, active infections

12. Known history of clinically significant liver disease, such as hepatitis b（HBV DNA ≥2000IU/mL (or ≥1×104 copies)）, hepatitis c, or cirrhosis

13. Prior anti-ITP emergency treatment within 2 weeks before randomization.

14. 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.

15. Any condition requiring anti-coagulant therapy or the regular use of any medication having effluence to Platelet function.

16. Exposure to Rituximab 14 weeks prior to randomization.

17. Treament with Chinese medicine within 1 week before randomization.

18. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450 isoform 1A2, and are identified as narrow therapeutic drugs within 14 days or 5 half-lives, whichever is longer, prior to initiation of study treatment.

19. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)

20. Allergic to study drug active ingredient or excipient

21. Subjects who have participated in clinical studies of drugs or invasive medical devices within 4 week before randomization

22. Subjects have severe psychological or mental abnormalities

23. Alcoholic or drug abuser

24. Female subjects during pregnancy and lactation

25. The investigator considered that the subjects were not suitable to participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hongyan Yin

Role: STUDY_DIRECTOR

Hutchison Medipharma Limited

Locations

Blood diseases hospital, Chinese academy of medical university

Tianjin, Tianjin Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 37028433 (View on PubMed)

Other Identifiers

2018-523-00CH1

Identifier Type: -

Identifier Source: org_study_id