The Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Subjects With Immune Thrombocytopenia (ITP)

Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06291415
• Other study ID #: 2022-523-GLOB1
• Status: Recruiting
• Phase: Phase 1
• Start date: April 2, 2024
• Est. completion date: November 2026

Study information

• Verified date: April 2024
• Source: Hutchmed
• Contact: Nick Lawn
• Phone: +1-973-306-4490
• Email: 2022-523-GLOB1[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.

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 information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: November 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Blood Coagulation Disorder
• Blood Coagulation Disorders
• Blood Platelet Disorder
• Blood Platelet Disorders
• Hematologic Diseases
• Hemorrhage
• Hemorrhagic Disorders
• Hemostatic Disorders
• Immune System Diseases
• Immune Thrombocytopenia
• Pathologic Processes
• Primary Immune Thrombocytopenia
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic
• Skin Manifestations
• Thrombocytopenia
• Thrombotic Microangiopathies

Intervention

Drug:
• HMPL-523
Syk inhibitor

Locations

Country	Name	City	State
Australia	Peninsula Private Hospital	Frankston	Victoria
Australia	The Perth Blood Institute (PBI) Hollywood Specialist Centre	West Perth	Western Australia
Germany	Marien Hospital Dusseldorf	Düsseldorf
Norway	Sykehuset Ostfold Kalnes (fosta) / Osfold Hospital Trust (MSL)	Grålum
Spain	Hospital del Mar Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	University de Burgos	Burgos
Spain	Clinica Universidad de Navarra	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital Gregorio Maranon Madrid	Madrid
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Morales Meseguer	Murcia
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Taussig Cancer Institute	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Hutchmed

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Norway,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of HMPL-523 in adult subjects with primary ITP	Calculated as the number and percent incidence of participants experiencing adverse events (AE).	week 1 - week 24
Primary	Dose Limiting Toxicities	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.	week 1 - week 4
Secondary	Cmax (maximum plasma drug concentration)	Blood samples will be obtained from all patients to determine maximum plasma drug concentration of HMPL-523 and metabolite M	week 1 and week 3
Secondary	AUCtau (area under the concentration-time curve over a dosage interval)	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	week 1 and week 3
Secondary	Tmax (time to reach maximum plasma drug concentration)	Blood samples will be obtained from all patients to determine time to reach maximum plasma concentration of HMPL-523 and metabolite M1	week 1 and week 3
Secondary	Cmin (minimum plasma drug concentration)	Blood samples will be obtained from all patients to determine minimum plasma concentration of HMPL-523 and metabolite M1	week 1 - week 20