Clinical trial NCT03951623: The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Immune Thrombocytopenia (ITP)
Keywords: syk inhibitor
ITP
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) .

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

Primary outcomes:
measure: Number of Participants with any Adverse Event
timeFrame: From first dose to within 28 days after the last dose
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: Day 15, 16, 29, 43 and 47
measure: Area under the concentration-time curve in a selected time interval (AUC0-t)
timeFrame: Day 15, 16, 29, 43 and 47
measure: Rate of Clinical Remission
timeFrame: Day 1 to 8 weeks treatment
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Blood diseases hospital, Chinese academy of medical university
state: Tianjin
Study officials:
affiliation: Hutchison Medipharma Limited
name: Hongyan Yin
role: STUDY_DIRECTOR
References: