This is a phase 3, double-blind, randomized, placebo-controlled, parallel group, adaptive, multicenter study planned to be conducted at multiple sites in North America, Canada, Taiwan and South Korea.
The purpose of this study is to measure the efficacy and safety of KP-001 compared with placebo in patients aged ≥2 years with common VM, common LM, or KTS/CLOVES syndrome.
An independent data monitoring committee (DMC) will be established to determine whether to discontinue or continue the study. It will also determine the redesign of the number of cases based on the result of the interim analysis.
The study will comprise the following:
* Screening Period: Up to 42 days prior to the first dose of study intervention. * Treatment Period 1: This is a double-blind period in which KP-001 100 mg (or lower dose depending on their body weight) or placebo will be administered to patients once daily after breakfast until Week 24. * Treatment Period 2: After 24 weeks of double blind treatment, all patients will switch to the KP-001 open label extension and treated up to Week 52. * Follow-up Visit: This visit will occur 30 days after the last dose of study intervention, and assessments will be performed per the SoA. * Discontinuation Visit: Patients who discontinue study intervention will be requested to continue participating in the study and assessments will be performed per the SoA. If the patients request to withdraw from the study, all tests and evaluations when possible will be performed at Discontinuation visit.
Patients aged 2 years or older at the time of consent or assent.
Patients diagnosed with ISSVA classification of common VM, common (cystic) LM (including mixed type consisting mainly of either VM or LM), or KTS/CLOVES syndrome.
Patients who cannot be cured by resection, who are difficult to resect based on the assessment of the Investigator, or who are considered refractory to available treatment by the Investigator, or who have a contraindication to available treatment.
Patients with at least one target lesion at least 4 cm in the longest diameter.
Patients with the following diseases: Simple telangiectatic malformation, lymphangiomatosis, lymphangiectatic malformation associated with Gorham's disease, lymphangiectasia, familial cutaneous mucocutaneous venous malformation, blue rubber ball-like nevus syndrome, M-CM/MCAP, CLAPO syndrome, Proteus syndrome, Parkes Weber syndrome, Sturge-Weber syndrome, Mafucci syndrome, Osler's disease, Cowden's disease, or Adams-Oliver syndrome.
Patients with uncontrolled diabetes mellitus (HbA1c ≥ 7.0%) or diseases with abnormal glucose metabolism (glycogenic diseases, galactosemia, primary lactose intolerance, etc).
Patients with ischemic heart disease, arrhythmia, or heart failure (NYHA III or IV).
Patients with gastrointestinal disorders that affect drug absorption, as determined by the Investigator.
Parallel
KP-001
DrugOral repeated dose 100mg or lower
Placebo
DrugOral repeated dose
The ratio of volume of target lesions based on MRI
To confirm the efficacy of KP-001 100 mg or lower based on body weight administered once daily in patients with vascular malformations (common VM, common LM, or KTS/CLOVES syndrome) in reducing volume of target lesions at 24 weeks
Change from baseline in NRS of symptom
To confirm the efficacy of KP-001 100 mg or lower based on body weight administered once daily in patients with vascular malformations (common VM, common LM, or KTS/CLOVES syndrome) on disease specific patient-reported outcomes from Week 20 through Week 24
The ratio of volume of target lesions based on MRI
To confirm the efficacy of KP-001 100 mg or lower based on body weight administered once daily in patients with vascular malformations (common VM, common LM, or KTS/CLOVES syndrome) in reducing volume of target lesions at 12 and 52 weeks
The proportion of patients defined as a responder at 12, 24, and 52 weeks
To confirm the efficacy of KP-001 100 mg or lower based on body weight administered once daily in patients with vascular malformations (common VM, common LM, or KTS/CLOVES syndrome) using response rate based on change in target lesion volume (MRI) at 12, 24, and 52 weeks
Change from baseline of Brief Pain Inventory short form
To evaluate the efficacy of KP-001 100 mg or lower based on body weight administered once daily in patients with vascular malformations (common VM, common LM, or KTS/CLOVES syndrome) on patient-reported outcomes at 4, 12, 24, 36, and 52 weeks
Change in D-dimer From Baseline to Week 24
Serum D-dimer will be measured as a coagulation biomarker of disease activity in patients with vascular malformations. The change from baseline to Week 24 will be evaluated to explore its clinical relevance.
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