NCT03951623已完成1 期
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
Hutchison Medipharma Limited1 个研究点 分布在 1 个国家目标入组 45 人开始时间: 2019年8月12日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Number of Participants with any Adverse Event
研究概览
简要总结
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.
详细描述
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) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form
- •18~75 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
排除标准
- •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.
- •Exposure to Rituximab 14 weeks prior to randomization.
- •Treament with Chinese medicine within 1 week before randomization.
- •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.
- •Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
- •Allergic to study drug active ingredient or excipient
- •Subjects who have participated in clinical studies of drugs or invasive medical devices within 4 week before randomization
- •Subjects have severe psychological or mental abnormalities
- •Alcoholic or drug abuser
- •Female subjects during pregnancy and lactation
- •The investigator considered that the subjects were not suitable to participate in the study
研究组 & 干预措施
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.
干预措施: HMPL-523 (Drug)
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.
干预措施: HMPL-523 (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with any Adverse Event
时间窗: 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
次要结局
- Rate of Clinical Remission(Day 1 to 8 weeks treatment)
- 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)
研究者
研究点 (1)
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