RecruitingPhase 1Phase 2NCT06975618

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)

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)


Sponsor

Haihe Biopharma Co., Ltd.

Enrollment

141 participants

Start Date

Aug 22, 2023

Study Type

INTERVENTIONAL

Conditions

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

Inclusion Criteria4

  • 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.

Exclusion Criteria3

  • 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.

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Interventions

DRUGCYH33

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.

DRUGPlacebo

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.


Locations(4)

Capital Institute of Pediatrics

Beijing, Beijing Municipality, China

Plastic Surgery Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Shanghai Ninth People Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

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NCT06975618


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