A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome

NCT07285005 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: KP-001-303undecided
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Venous Malformations; Lymphatic Malformations; Klippel-Trenaunay Syndrome; CLOVES Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  pre-does and at 24weeks post-dose

Secondary Outcomes (19)

• Change from baseline in NRS of symptom

  Week 20 through Week 24

• The ratio of volume of target lesions based on MRI

  Pre-does and at 12 and 52 weeks post-dose

• The proportion of patients defined as a responder at 12, 24, and 52 weeks

  pre-does and at 12, 24 and 52 weeks post-dose

• Change from baseline of Brief Pain Inventory short form

  pre-does and at 4, 12, 24, 36, and 52 weeks post-dose

• Change from baseline of PGI-S (Patient Global Impression of Severity and PGI-I (Patient Global Impression of Improvement)

  pre-does and at 4, 12, 24, 36, and 52 weeks post-dose

Other Outcomes (1)

• Change in D-dimer From Baseline to Week 24

  up to 52 weeks post-dose

Study Arms (2)

KP-001

EXPERIMENTAL

Drug: KP-001; Drug: Placebo

placebo

PLACEBO COMPARATOR

Drug: KP-001; Drug: Placebo

Interventions

KP-001 DRUG

Oral repeated dose 100mg or lower

KP-001; placebo

Placebo DRUG

Oral repeated dose

KP-001; placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 at least one MRI-volumetric target lesion at screening that is determined to be evaluable by the central imaging evaluator.
• Patients with symptomatic disease, defined as:
• ・ For patients ≥8 years old: Pain NRS of ≥1 and ≤8 score at the screening visit will be eligible only if their daily pain NRS recorded via ePRO from screening to Day 1 (Week 0) does not show a maximum absolute change of ≥6 points. If patients are taking analgesic medication, there must be no change in the type or dosage of analgesic during the screening period. If patients do not have qualifiable pain, then Fatigue or Bleeding/Oozing NRS of ≥1 and ≤8 score at the screening visit is required. Patients with ≥6 points absolute change in pain NRS are eligible if at least one of either Fatigue OR Bleeding/Oozing NRS is ≥1 and ≤8.
• Patients whose pain from vascular malformations has been stable for at least 30 days prior to screening and, if taking analgesic medication, does not require a change in the type of analgesic medication or its dosage during the screening period.
• Patients who agree that they or their partner (if either of them is of childbearing potential) will use appropriate contraception (eg, condom and spermicide combination, low-dose pills or other appropriate contraceptive methods, sterilization, intrauterine device) from the time of consent until 90 days after the last dose of study intervention.
• Patients or their LAR who are able to give age-appropriate informed consent at the time of screening.
• Patients who are judged by the Investigator to be able to comply with the instructions of the Investigator and the study coordinator regarding the matters specified in the protocol, such as the use of study intervention and concomitant use of prohibited drugs.

You may not qualify if:

• 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.
• Patients with concomitant or pre-existing serious drug hypersensitivity to PI3Kα inhibitors.
• Patients with allergy history of grade ≥ 3 and/or history of grade ≥ 3 allergic reactions to drug.
• Patients with known hypersensitivity to quinine.
• Patients with concomitant or pre-existing alcohol or drug abuse.
• Patients with ANC of \<1.5×10\^9/L.
• Patients with acute or chronic kidney disease and/or dialysis dependence. Patients with screening eGFR \<30 mL/min/1.73m\^2 using the beside Schwartz equation for patients aged \<18 years of age or CKD-EPI formula for \>18 years of age will also be excluded.
• Patients who are judged by the Investigator to have hepatic impairment.
• Patients with total bilirubin ≥1.5×ULN for age (unless there is a history of Gilbert Syndrome), ALT ≥2×ULN for age, or AST ≥2×ULN for age will be excluded.
• Patients with target lesion infection that require treatment within 28 days prior to screening.
• Patients who have undergone invasive treatment, including sclerotherapy or laser therapy, for the target lesion within 84 days prior to screening.
• Patients who have used other PI3Kα inhibitors or sirolimus within 84 days prior to screening.

Sponsors & Collaborators

• Kaken Pharmaceutical: lead

MeSH Terms

Conditions

Lymphatic Abnormalities; Klippel-Trenaunay-Weber Syndrome; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Angiomatosis; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Sr. Clinical Trial Manager, Clinical Operations

CONTACT

+818059831020; jmisajon@aadibio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 16, 2025
• Study Start: February 26, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 19, 2025

Record last verified: 2025-12