Autoimmune Diseases, Blood Coagulation Disorder, Blood Platelet Disorder, Hematologic Diseases, Hemorrhage, Hemorrhagic Disorders, Immune System Diseases, Immune Thrombocytopenia, ITP - Immune Thrombocytopenia, Pathologic Processes, Primary Immune Thrombocytopenia, Purpura, Purpura, Thrombocytopenic, Purpura, Thrombocytopenic, Idiopathic, Skin Manifestations, Thrombocytopenia, Thrombotic Microangiopathies
Conditions
Keywords
ITP, sovleplenib
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.
Interventions
DRUGHMPL-523
Syk inhibitor
Sponsors
Hutchmed
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1: Dose escalation stage - 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) Part 2: subjects will be randomized in a 1:1 ratio between the 2 dose levels recommended by the SRC to better understand the exposure/efficacy/toxicity relationship. At the end of Part 2, the SRC will evaluate the safety, tolerability, preliminary efficacy, and PK data to determine the Recommended Phase 3 dose (RP3D) of HMPL-523.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects may be enrolled in this study only if they satisfy all the following criteria: 1. Adult male or female subjects ≥18 years of age 2. Diagnosis of ITP, with a duration of disease of at least 3 months prior to randomization or enrollment 3. Intolerance or insufficient response or recurrence after at least 1 prior ITP treatment (excluding splenectomy) 4. Response (defined as achieved a platelet count ≥50 × 109/L) to at least 1 prior ITP therapy (including splenectomy) 5. Adequate hematologic, hepatic and renal function
Exclusion criteria
Subjects are not eligible for enrollment into this study if any one of the following criteria are met: 1. Evidence of the presence of secondary causes of ITP 2. Clinically serious hemorrhage requiring immediate adjustment of platelets 3. Known history of vital organ transplantation or hematopoietic stem-cell transplantation or chimeric antigen receptor T-cells (CAR-T) therapy 4. Splenectomy within 12 weeks prior to enrollment 5. Presence of active malignancy unless deemed cured by adequate treatment. 6. History of serious cardiovascular disease corrected QT interval (QTcF) ≥450 ms 7. Uncontrolled hypertension 8. Being unsuitable to participate in this study as considered by investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Australia, Germany, Norway, Spain, United States
Outcome results
None listed