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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03951623
Recruitment Status : Recruiting
First Posted : May 15, 2019
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

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.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenia (ITP) Drug: HMPL-523 Drug: Placebo Phase 1

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) .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Active Comparator: 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.
Drug: HMPL-523
HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

Placebo Comparator: placebo arm
Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.
Drug: HMPL-523
HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

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




Primary Outcome Measures :
  1. Number of Participants with any Adverse Event [ Time Frame: From first dose to within 28 days after the last dose ]
    Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Maximum plasma concentration (Cmax)

  2. Area under the concentration-time curve in a selected time interval (AUC0-t) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Area under the concentration-time curve in a selected time interval (AUC0-t)

  3. Rate of Clinical Remission [ Time Frame: Day 1 to 8 weeks treatment ]
    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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03951623


Contacts
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Contact: jiayi Mai 086-021-20673063 Jiayim@hmplglobal.com

Locations
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China, Tianjin
Blood diseases hospital, Chinese academy of medical university Recruiting
Tianjin, Tianjin, China, 300000
Contact: Renchi Yang       rcyang65@163.com   
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Hongyan Yin Hutchison MediPharma
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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT03951623    
Other Study ID Numbers: 2018-523-00CH1
First Posted: May 15, 2019    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hutchison Medipharma Limited:
syk inhibitor
ITP
Additional relevant MeSH terms:
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Thrombocytopenia
Immune System Diseases
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations