Skip to main content
OpenTrials
Recruiting

NCT Number: 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)

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)

Recruiting

Interested in participating?

Request Info

Key information

Conditions

PIK3CA-related Overgrowth Spectrum (PROS) PIK3CA-related Vascular Malformations (PRVM)

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Capital Center for Children's Health, Capital Medical University, Beijing, Beijing Municipality, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key inclusion criteria:

  • The patient or the patient's legal guardian (if applicable) voluntarily signs the Informed Consent Form.
  • At the time of signing the informed consent, adult patients should be ≥18 years old (or meet the legal adult age according to local regulations), and adolescent patients should be ≥12 years old and <18 years old (or meet the legal definition of adolescent according to local regulations; additionally, adolescent patients should weigh ≥35 kg).
  • The patient is diagnosed with PIK3CA-related overgrowth spectrum (PROS) or PIK3CA-related vascular malformations (PRVM), and provides a report confirming PIK3CA mutation detected by local laboratory or the Sponsor-designated central laboratory, with at least one measurable lesion related to PROS or PRVM.
  • Patients should demonstrate adequate organ and bone marrow function during the 28-day screening period.

Key exclusion criteria:

  • PROS patients presenting solely with isolated macrodactyly, epidermal nevi/nevus, and megalencephaly (only one clinical feature or any combination of these three features) without other PROS-related lesions.
  • Patients who have received any systemic treatment for PROS or PRVM within 8 weeks prior to the first dose of study drug, or any drug treatment for PROS or PRVM (e.g., mTOR inhibitors) within 28 days prior to the first dose of study drug.
  • Patients who have previously received any PI3K inhibitor treatment.

Treatment and study plan

CYH33

Drug

CYH33: Participants will receive oral CYH33 once daily. The starting dose for adults in Phase I is 10 mg QD; adolescents begin at 5 mg QD. In Phase II, patients will receive RP2D determined in the Phase I study.

Placebo

Drug

Placebo: Matching placebo tablets will be administered once daily during the double-blind period of the Phase II PRVM cohort. Patients randomized to placebo will switch to CYH33 at the end of the blinded phase.

Primary outcomes

  1. Phase I: The maximum tolerated dose (MTD) and/or phase II recommended dose (RP2D)

    Time frame: 27 weeks

    To evaluate the safety and tolerability of CYH33 and determine the maximum tolerated dose (MTD) and/or phase II recommended dose (RP2D) of CYH33 in adult and adolescent patients

  2. Phase II PROS Cohort: BIRC-assessed objective response rate (ORR) at Week 24

    Time frame: Baseline to 24weeks

    Proportion of patients achieving ≥20% reduction from baseline in the sum of target lesion volumes, with no progression of non-target lesions and no new lesions, as assessed by blinded independent review committee (BIRC).

  3. Phase II PRVM Cohort: BIRC-assessed objective response rate (ORR) at Week 24

    Time frame: Baseline to 24weeks

    Proportion of patients achieving ≥20% reduction from baseline in the sum of target lesion volumes, with no progression of non-target lesions and no new lesions, as assessed by blinded independent review committee (BIRC).

Secondary outcomes

  1. Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Area Under the Curve from 0 to 24 hours (AUC0-24h)

    Time frame: Pre-dose and at 1, 2, 4, 6, 8, and 24 hours post-dose on Day 1 and Day 29.

    AUC0-24h of CYH33 and its metabolite I27 following drug administration will be assessed.

  2. Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Maximum Concentration (Cmax)

    Time frame: Pre-dose and at 1, 2, 4, 6, 8, and 24 hours post-dose on Day 1 and Day 29.

    Cmax of CYH33 and its metabolite I27 following drug administration will be assessed.

  3. Phase I: Pharmacokinetics of CYH33 and its metabolite I27 in the study population: Minimum Concentration (Cmin)

    Time frame: Pre-dose on Day 29.

    Cmin of CYH33 and its metabolite I27 following drug administration will be assessed.

  4. Phase I: Pharmacokinetics of CYH33 and its metabolites in the study population: Time to Maximum Concentration (Tmax)

    Time frame: Pre-dose and at 1, 2, 4, 6, 8, and 24 hours post-dose on Day 1 and Day 29.

    Tmax of CYH33 and its metabolite I27 following drug administration will be assessed.

  5. Phase I: Pharmacokinetics of CYH33 in the study population: Steady-State Apparent Clearance (CLss/F)

    Time frame: Pre-dose and at 1, 2, 4, 6, 8, and 24 hours post-dose on Day 1 and Day 29.

    CLss/F of CYH33 following drug administration will be assessed.

  6. Phase I: The response rate and target lesion volume reduction rate as assessed by the investigators at each dose level

    Time frame: week 27

    A responder is defined as a ≥ 20% reduction in target lesion volume from baseline and in absence of progression of non-target lesions and without new lesions. The proportion of patients with reduced target lesion volume compared to baseline will also be assessed.

  7. 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

    Time frame: Up to approximately 48 months

    Pain is categorized into 11 levels from 0 to 10, where 0 indicates no pain at all and 10 indicates the most severe pain imaginable. Patients should assess and record their pain levels over the past 24 hours in the patient diary at each scheduled assessment visit.

  8. 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

    Time frame: Up to approximately 48 months

    Patients will compare their global impression of symptom changes with the pretreatment status, then categorize them into the following 7 grades: significantly relieved, moderately relieved, minimally relieved, no change, minimally worse, moderately worse, or significantly worse at each scheduled assessment visit.

  9. Phase I: The changes from baseline in the quality of life scores at each dose level, based on the patient-reported outcome (PRO) diary

    Time frame: Up to approximately 48 months

    The Quality of Life Scale (EQ-5D-5L) consists of two parts. Part 1 assesses five quality-of-life-related indicators, with each indicator graded into five distinct levels for self-evaluation by the patient. Part 2 consists of patients' self-assessment of health status, with a maximum score of 100 points and a minimum score of 0 points.

  10. Phase I: Frequency and severity of adverse events

    Time frame: Up to approximately 48 months

    The type, incidence, and severity of adverse events (AEs) (assessed according to the CTCAE Version 5.0 criteria).

  11. Phase II : BIRC-assessed ORR at Week 48 (PROS cohort and PRVM cohort)

    Time frame: Week 48

    BIRC-assessed ORR at Week 48 (PROS cohort and PRVM cohort) Time Frame: From start of CYH33 treatment to Week 48

  12. Phase II: BIRC-assessed ORR at Week 8 (Double-blind Period in PRVM cohort)

    Time frame: Week27

    BIRC-assessed ORR at Week 8 (Double-blind Period in PRVM cohort) Time Frame: From randomization to Week 8

  13. Phase II: BIRC-assessed ORR at Weeks 8 and 16 (PROS cohort and PRVM cohort)

    Time frame: Weeks 8 and Week 16

    BIRC-assessed ORR at Weeks 8 and 16 (PROS cohort and PRVM cohort) Time Frame: From start of CYH33 treatment to Weeks 8 and 16

  14. Phase II : Change from Baseline in Target Lesion Volume (PROS cohort and PRVM cohort)

    Time frame: Up to approximately 48 months

    Change from Baseline in Target Lesion Volume (PROS cohort and PRVM cohort) Time Frame: From start of CYH33 treatment to Week 48

  15. Phase II: Investigator-assessed overall clinical response (PROS cohort and PRVM cohort)

    Time frame: Up to approximately 48 months

    Investigator-assessed overall clinical response (PROS cohort and PRVM cohort) Time Frame: From start of CYH33 treatment to Week 48

  16. Phase II: Change from Baseline in Patient-Reported Outcomes (PROS cohort and PRVM cohort)

    Time frame: Up to approximately 48 months

    Change from Baseline in Patient-Reported Outcomes (PROS cohort and PRVM cohort) Time Frame: Up to approximately 48 months

  17. Phase II: Safety and Tolerability of CYH33 (PROS cohort and PRVM cohort)

    Time frame: Up to approximately 48 months

    Safety and Tolerability of CYH33 (PROS cohort and PRVM cohort) Time Frame: Up to approximately 48 months

  18. Phase II :Plasma Drug Concentrations of CYH33 and Metabolite I27

    Time frame: Up to 5 cycles (approximately 20 weeks)

    Plasma Drug Concentrations of CYH33 and Metabolite I27

Study contacts

Contact information is provided by the study sponsor or research team.

Xiaoxi Lin, MD

CONTACT

[email protected]

+86-13701997136

Sponsors and collaborators

Lead sponsor

Haihe Biopharma Co., Ltd.

Industry

Registry information

Official study 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)

Important dates

Study start
2023
Primary completion
2029
Study completion
2029
First posted
May 16, 2025
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.