Clinical trial NCT06291415: The Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Subjects With Immune Thrombocytopenia (ITP)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Immune Thrombocytopenia
Blood Platelet Disorder
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorder
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Primary Immune Thrombocytopenia
ITP - Immune Thrombocytopenia
Keywords: ITP
sovleplenib
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of HMPL-523 in adult subjects with primary ITP
timeFrame: week 1 - week 24
measure: Dose Limiting Toxicities
timeFrame: week 1 - week 4
Secondary outcomes:
measure: Cmax (maximum plasma drug concentration)
timeFrame: week 1 and week 3
measure: AUCtau (area under the concentration-time curve over a dosage interval)
timeFrame: week 1 and week 3
measure: Tmax (time to reach maximum plasma drug concentration)
timeFrame: week 1 and week 3
measure: Cmin (minimum plasma drug concentration)
timeFrame: week 1 - week 20
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Childrens Hospital of California
state: California
city: Georgetown
country: United States
facility: Georgetown University Medical Center - Georgetown Lombardi Comprehensive Cancer Center
state: Delaware
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Greenville
country: United States
facility: East Carolina University, Brody School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Taussig Cancer Institute
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute
state: Oklahoma
city: San Antonio
country: United States
facility: Texas Oncology San Antonio Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington (UW) Medical Center
state: Washington
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: West Perth
country: Australia
facility: The Perth Blood Institute (PBI) Hollywood Specialist Centre
state: Western Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Canberra
country: Australia
facility: Canberra Hospital
city: Berlin
country: Germany
facility: Charite university
city: Düsseldorf
country: Germany
facility: Marien Hospital Dusseldorf
city: Göttingen
country: Germany
facility: UMG Gottingen Hämatologie
city: Lübeck
country: Germany
facility: University Hospital of Schleswig-Holstein, Department of Haematology and Oncology
city: Grålum
country: Norway
facility: Sykehuset Ostfold Kalnes (fosta) / Osfold Hospital Trust (MSL)
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barcelona
country: Spain
facility: Hospital del Mar Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Burgos
country: Spain
facility: University de Burgos
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon Madrid
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
Study officials:
affiliation: Hutchmed
name: William Schelman, MD, PhD
role: STUDY_DIRECTOR
References: