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

Immune Thrombocytopenia (ITP) Clinical Trial

Official title:

The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523, a Syk Inhibitor in Adult Patients of Immune Thrombocytopenia: a Randomized, Double Blinded, Placebo Controlled Phase Ib Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03951623
• Other study ID #: 2018-523-00CH1
• Status: Recruiting
• Phase: Phase 1
• Start date: August 12, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2020
• Source: Hutchison Medipharma Limited
• Contact: jiayi Mai
• Phone: 086-021-20673063
• Email: Jiayim[@]hmplglobal.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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) .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

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

Locations

Country	Name	City	State
China	Blood diseases hospital, Chinese academy of medical university	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maximum plasma concentration (Cmax)	Maximum plasma concentration (Cmax)	Day 15, 16, 29, 43 and 47
Secondary	Area under the concentration-time curve in a selected time interval (AUC0-t)	Area under the concentration-time curve in a selected time interval (AUC0-t)	Day 15, 16, 29, 43 and 47
Secondary	Rate of Clinical Remission	Rate of Clinical Remission was defined as the proportion of patients with two consecutive visits in the first 8 weeks (including the 8th week) during the medication period, platelet count =30×10^9/L, and a 2-fold increase from baseline (no emergency treatment during the period)	Day 1 to 8 weeks treatment