Clinical trial NCT06975618: Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Patients With PIK3CA-related Overgrowth Spectrum (PROS) and PIK3CA-related Vascular Malformations (PRVM)
Official title: A Phase I/II, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Efficacy of CYH33 (a Selective PI3Kα Inhibitor) in Patients With PIK3CA-related Overgrowth Spectrum (PROS) and PIK3CA-related Vascular Malformations (PRVM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: PIK3CA-Related Overgrowth Spectrum (PROS)
PIK3CA-related Vascular Malformations (PRVM)
Lead sponsor: Haihe Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 130
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a multi-center, open-label, single arm, phase I/II study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 in patients with PIK3CA-related overgrowth spectrum (PROS) and PIK3CA-related vascular malformations (PRVM)


Eligibility criteria: Inclusion Criteria:

* The patient or the patient's guardian (if applicable) voluntarily signs the Informed Consent Form.
* At the time of signing the Informed Consent, the age of adult patients should be ≥ 18 years, and the age of adolescent patients should be ≥ 12 years and \< 18 years of age.
* Patient diagnosed with PIK3CA-related overgrowth spectrum (PROS) or PIK3CA-related vascular malformation (PRVM).
* Patients should be tested to have adequate organ and bone marrow function, within 28 days of the screening period.

Exclusion Criteria:

* Patients who have received any prior treatment with PI3K or AKT inhibitors.
* Received a blood transfusion or platelet transfusion within 2 weeks prior to the administration of the investigational drug.
* Patients with clinically significant cardiovascular disease.

Primary outcomes:
measure: Phase I: The maximum tolerated dose (MTD) and/or phase II recommended dose (RP2D)
timeFrame: 27 weeks
measure: Phase II: The response rate as assessed by BIRC in each cohort
timeFrame: week 27
Secondary outcomes:
measure: Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Area Under the Curve from 0 to 24 hours (AUC0-24h)
timeFrame: Pre-dose and at 1, 2, 4, 6, 8, and 24 h post-dose on Cycle1Day1 and Cycle2Day1
measure: Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Maximum Concentration (Cmax)
timeFrame: Pre-dose and at 1, 2, 4, 6, 8, and 24 h post-dose on Cycle1Day1 and Cycle2Day1
measure: Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Minimum Concentration (Cmin)
timeFrame: Pre-dose on Cycle2Day1
measure: Phase I: Pharmacokinetics of CYH33 and its metabolites in the study population: Time to Maximum Concentration (Tmax)
timeFrame: Pre-dose and at 1, 2, 4, 6, 8, and 24 h post-dose on Cycle1Day1 and Cycle2Day1
measure: Phase I: Pharmacokinetics of CYH33 in the study population: Steady-State Apparent Clearance (CLss/F)
timeFrame: Pre-dose and at 1, 2, 4, 6, 8, and 24 h post-dose on Cycle2Day1
measure: Phase I: The response rate and target lesion volume reduction rate as assessed by the investigators at each dose level
timeFrame: week 27
measure: Phase I: The changes from baseline in the Brief Pain Inventory (BPI) Worst Pain Intensity Numerical Rating score at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase I: The changes from baseline in the Patient Global Impression of Change scale at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase I: The changes from baseline in the quality of life scores at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase I: Frequency and severity of adverse events
timeFrame: Up to approximately 48 months
measure: Phase II: The reduction rate of target lesion volume as assessed by BIRC in each cohort
timeFrame: Week27
measure: Phase II: The response rate and reduction rate of target lesion volume as assessed by the investigators in each cohort
timeFrame: Week27
measure: Phase II: The changes from baseline in the Brief Pain Inventory (BPI) Worst Pain Intensity Numerical Rating score at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase II: The changes from baseline in the Patient Global Impression of Change scale at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase II: - The changes from baseline in the quality of life scores at each dose level, based on the patient-reported outcome (PRO) diary
timeFrame: Up to approximately 48 months
measure: Phase II: Frequency and severity of adverse events
timeFrame: Up to approximately 48 months
measure: Phase II: Plasma concentrations of CYH33 and its metabolite I27 in the study population
timeFrame: 4 h post-dose on Day 1 of Cycles 1, 2, 3, 4, and 5, and on the day of the EOT visit
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Institute of Pediatrics
state: Beijing
city: Beijing
country: China
facility: Plastic Surgery Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Shanghai
country: China
facility: Shanghai Ninth People Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References: