The Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Subjects With Immune Thrombocytopenia (ITP)
- Conditions
- Blood Platelet DisorderImmune System DiseasesSkin ManifestationsThrombocytopeniaImmune ThrombocytopeniaAutoimmune DiseasesHemorrhageHematologic DiseasesPrimary Immune ThrombocytopeniaITP - Immune Thrombocytopenia
- Interventions
- Registration Number
- NCT06291415
- Lead Sponsor
- Hutchmed
- Brief Summary
This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.
- Detailed Description
This study is a Phase 1b, open-label, multicenter, single-arm study to evaluate the safety, tolerability, and preliminary efficacy of HMPL-523 in adult subjects with primary ITP diagnosed at least 3 months prior to enrollment or randomization.
In the dose escalation stage (Part 1), subjects will receive one of 3 dose levels of HMPL-523 to determine the recommended dose of HMPL-523 for the randomized dose optimization- stage (Part 2).
At the end of Part 1, 2 dose levels will be selected to be used in the dose-optimization stage (Part 2) of the study. In Part 2 of the study, subjects will be randomized in a 1:1 ratio between the 2 dose levels to better understand the exposure/efficacy/toxicity relationship.
At the end of Part 2, the Recommended Phase 3 dose (RP3D) of HMPL-523 will be determined based on the safety, efficacy and PK data.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
Subjects may be enrolled in this study only if they satisfy all the following criteria:
- Adult male or female subjects ≥18 years of age
- Diagnosis of ITP, with a duration of disease of at least 3 months prior to randomization or enrollment
- Intolerance or insufficient response or recurrence after at least 1 prior ITP treatment (excluding splenectomy)
- Response (defined as achieved a platelet count ≥50 × 109/L) to at least 1 prior ITP therapy (including splenectomy)
- Adequate hematologic, hepatic and renal function
Subjects are not eligible for enrollment into this study if any one of the following criteria are met:
- Evidence of the presence of secondary causes of ITP
- Clinically serious hemorrhage requiring immediate adjustment of platelets
- Known history of vital organ transplantation or hematopoietic stem-cell transplantation or chimeric antigen receptor T-cells (CAR-T) therapy
- Splenectomy within 12 weeks prior to enrollment
- Presence of active malignancy unless deemed cured by adequate treatment.
- History of serious cardiovascular disease corrected QT interval (QTcF) ≥450 ms
- Uncontrolled hypertension
- Being unsuitable to participate in this study as considered by investigators
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose escalation HMPL-523 Part 1 will consist of the following 3 dose levels: 300, 400, and 500 mg once daily (QD). Dose optimization stage HMPL-523 In part 2 subjects will be randomized in a 1:1 ratio between the 2 dose levels selected at the end of part 1.
- Primary Outcome Measures
Name Time Method Safety and tolerability of HMPL-523 in adult subjects with primary ITP week 1 - week 24 Calculated as the number and percent incidence of participants experiencing adverse events (AE).
Dose Limiting Toxicities week 1 - week 4 Defined as an adverse event AE that meets protocol defined Dose Limiting Toxicities (DLT) criteria during the DLT assessment window (first 28 days), unless clearly unrelated to ITP drugs.
- Secondary Outcome Measures
Name Time Method Cmax (maximum plasma drug concentration) week 1 and week 3 Blood samples will be obtained from all patients to determine maximum plasma drug concentration of HMPL-523 and metabolite M
Tmax (time to reach maximum plasma drug concentration) week 1 and week 3 Blood samples will be obtained from all patients to determine time to reach maximum plasma concentration of HMPL-523 and metabolite M1
AUCtau (area under the concentration-time curve over a dosage interval) week 1 and week 3 Blood samples will be obtained from all patients to determine area under the concentration time curve over periodic dosing intervals for HMPL-523 and metabolite M1
Cmin (minimum plasma drug concentration) week 1 - week 20 Blood samples will be obtained from all patients to determine minimum plasma concentration of HMPL-523 and metabolite M1
Trial Locations
- Locations (28)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Washington (UW) Medical Center
🇺🇸Seattle, Washington, United States
The Perth Blood Institute (PBI) Hollywood Specialist Centre
🇦🇺West Perth, Western Australia, Australia
Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Canberra Hospital
🇦🇺Canberra, Australia
East Carolina University, Brody School of Medicine
🇺🇸Greenville, North Carolina, United States
Charite university
🇩🇪Berlin, Germany
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Sykehuset Ostfold Kalnes (fosta) / Osfold Hospital Trust (MSL)
🇳🇴Grålum, Norway
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Gregorio Maranon Madrid
🇪🇸Madrid, Spain
Hospital Infanta Leonor
🇪🇸Madrid, Spain
University de Burgos
🇪🇸Burgos, Spain
Clinica Universidad de Navarra
🇪🇸Madrid, Spain
Marien Hospital Dusseldorf
🇩🇪Düsseldorf, Germany
University Hospital of Schleswig-Holstein, Department of Haematology and Oncology
🇩🇪Lübeck, Germany
Childrens Hospital of California
🇺🇸Irvine, California, United States
Georgetown University Medical Center - Georgetown Lombardi Comprehensive Cancer Center
🇺🇸Georgetown, Delaware, United States
Peninsula Private Hospital
🇦🇺Frankston, Victoria, Australia
UMG Gottingen Hämatologie
🇩🇪Göttingen, Germany
Hospital del Mar Barcelona
🇪🇸Barcelona, Spain
Hospital Morales Meseguer
🇪🇸Murcia, Spain
Oklahoma Cancer Specialists and Research Institute
🇺🇸Tulsa, Oklahoma, United States
Oslo University Hospital
🇳🇴Oslo, Norway
Texas Oncology San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States