A Multicenter, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523, a Syk Inhibitor, in Adult Subjects With Immune Thrombocytopenia
Overview
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- Hutchmed
- Enrollment
- 48
- Locations
- 28
- Primary Endpoint
- Safety and tolerability of HMPL-523 in adult subjects with primary ITP
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Dose escalation
Part 1 will consist of the following 3 dose levels: 300, 400, and 500 mg once daily (QD).
Intervention: HMPL-523 (Drug)
Dose optimization stage
In part 2 subjects will be randomized in a 1:1 ratio between the 2 dose levels selected at the end of part 1.
Intervention: HMPL-523 (Drug)
Outcomes
Primary Outcomes
Safety and tolerability of HMPL-523 in adult subjects with primary ITP
Time Frame: week 1 - week 24
Calculated as the number and percent incidence of participants experiencing adverse events (AE).
Dose Limiting Toxicities
Time Frame: 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 Outcomes
- Cmax (maximum plasma drug concentration)(week 1 and week 3)
- Tmax (time to reach maximum plasma drug concentration)(week 1 and week 3)
- AUCtau (area under the concentration-time curve over a dosage interval)(week 1 and week 3)
- Cmin (minimum plasma drug concentration)(week 1 - week 20)