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PIK3CA-Related Overgrowth Spectrum (PROS)Phase 1/2NCT06975618

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 1/2 study testing CYH33 in people with PIK3CA-Related Overgrowth Spectrum (PROS) and PIK3CA-related Vascular Malformations (PRVM), run by Haihe Biopharma Co., Ltd. at 15 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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) Read more about this study

Who is it for?
Any age
What is being tested?
CYH33
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
141 participants
Where
15 sitesin 2 countries
Study dates
22 Aug 2023to 31 Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Xiaoxi Lin, MD contact

+86-13701997136

linxiaoxi@126.com

15 sites in 2 countries

China8 sites, 8 recruiting

  • Capital Center for Children's Health, Capital Medical University

    Beijing, Beijing Municipality, 100000

    Ying Gao, MD, +86-15210250269, sccgcw@sina.com

    Ying Gao, MD

    Recruiting

  • Plastic Surgery Hospital, Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality, 100144

    Yan Yan, MD, +86-13661348184, yanyan201606@163.com

    Yan Yan, MD

    Recruiting

  • The Second Xiangya Hospital of Central South University

    Changsha, Hunan, 410011

    Chang Shu

    +86-13607444222, changshu01@yahoo.com

    Recruiting

  • West China Hospital of Sichuan University

    Chengdu, Sichuan, 610041

    Xian Jiang, MD, +86-18980601693, jx0133@qq.com

    Recruiting

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

    Xiaosong Chen, +86-13365910035, chenxiaosong74@163.com

    Xiaosong Chen

    Recruiting

  • Guangzhou Women and Children's Medical Center

    Guangzhou, Guangdong, 510000

    Haibo Li, MD, +86-13711745928, 448214152@qq.com

    Haibo Li, MD

    Not yet recruiting

  • Shanghai Ninth People Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, Shanghai Municipality, 200011

    Xiaoxi Lin, MD, +86-13701997136, linxiaoxi@126.com

    Xiaoxi Lin, MD

    Recruiting

  • Henan Provincial People's Hospital

    Zhengzhou, Henan, 450003

    Jianbo Wang, MD

    Jianbo Wang, MD

    Recruiting

Other trials in China

Japan7 sites, 7 recruiting

  • Gifu University Hospital

    Gifu, 501-1194

    Ozeki Michio Associate Professor, +81-58-230-6000, ozeki.michio.j5@f.gifu-u.ac.jp

    Ozeki Michio, Associate Professor

    Recruiting

  • National Hospital Organization Kobe Medical Center

    Kobe, Hyōgo, 654-0155

    Nomura Tadashi, Director of department, +81-78-791-0111, tadnomura@gmail.com

    Nomura Tadashi, Director of department

    Recruiting

  • Shinshu University Hospital

    Matsumoto, Nagano, 390-8621

    Yuzuriha Shunsuke

    Yuzuriha Shunsuke

    Recruiting

  • Kyorin University Hospital

    Mitaka, Tokyo, 181-8611

    Ozaki Mine, Professor, +81-422-47-5511, zakimin0108@gmail.com

    Ozaki Mine, Professor

    Recruiting

  • Tonan Hospital

    Sapporo, Hokkaido, 060-0004

    Sasaki Satoru, +81-11-231-2121, satokyan99@yahoo.co.jp

    Sasaki Satoru

    Recruiting

  • Tohoku University Hospital

    Sendai, Miyagi, 980-8574

    Imai Yoshimichi Professor, +81-22-717-7000, yoshimichi.imai.d6@tohoku.ac.jp

    Imai Yoshimichi, Professor

    Recruiting

  • Yokohama City University Hospital

    Yokohama, Kanagawa, 236-0004

    Hayashi Ayato, Professor, 81-45-787-2800, hayashi.aya.jb@yokohama-cu.ac.jp

    Hayashi Ayato, Professor

    Recruiting

Other trials in Japan

About this study

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)

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)

Being tested
CYH33, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CYH33Drug

    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.

  • PlaceboDrug

    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.

Study groups in NCT06975618
Study groupRoleWhat they receive
Arm 1：Adult cohort:；ExperimentalPhase I Adult Cohort: Adult patients with PIK3CA-related overgrowth spectrum (PROS) or PIK3CA-related vascular malformations (PRVM) will receive escalating oral doses of CYH33 to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). Expansion cohorts may be opened to further assess safety, tolerability, pharmacokinetics, and preliminary efficacy.
Receives: Drug: CYH33
Arm 2: Phase I Adolescent CohortExperimentalPhase I Adolescent Cohort: Adolescent patients with PIK3CA-related overgrowth spectrum (PROS) or PIK3CA-related vascular malformations (PRVM) will receive escalating oral doses of CYH33 to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). Expansion cohorts may be opened to further assess safety, tolerability, pharmacokinetics, and preliminary efficacy.
Receives: Drug: CYH33
Arm 3 : Phase II PROS CohortExperimentalPhase II PROS Cohort: An open-label, single-arm cohort. Adult and adolescent patients with PROS will receive CYH33 at RP2D. Dose escalation may be allowed based on tolerability and clinical assessment. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal.
Receives: Drug: CYH33
Arm 4 : Phase II PRVM CohortExperimentalPhase II PRVM Cohort: Adult and adolescent patients with PRVM will be randomized 2:1 to CYH33 or placebo during double-blind period. After 8 weeks of treatment, all patients will enter an open-label extension phase to receive CYH33. Treatment continues until disease progression, unacceptable toxicity, or withdrawal.
Receives: Drug: CYH33; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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

    Measured: 27 weeks

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

    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).

    Measured: Baseline to 24weeks

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

    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).

    Measured: Baseline to 24weeks

Secondary outcomes (18)

  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)

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

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

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

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

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

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

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

    Measured: Pre-dose on Day 29.

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

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

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

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

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

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

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

    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.

    Measured: week 27

  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

    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.

    Measured: Up to approximately 48 months

  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

    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.

    Measured: Up to approximately 48 months

  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

    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.

    Measured: Up to approximately 48 months

  10. Phase I: Frequency and severity of adverse events

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

    Measured: Up to approximately 48 months

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

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

    Measured: Week 48

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

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

    Measured: Week27

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

    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

    Measured: Weeks 8 and Week 16

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

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

    Measured: Up to approximately 48 months

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

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

    Measured: Up to approximately 48 months

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

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

    Measured: Up to approximately 48 months

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

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

    Measured: Up to approximately 48 months

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

    Plasma Drug Concentrations of CYH33 and Metabolite I27

    Measured: Up to 5 cycles (approximately 20 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2025
  2. Study start22 Aug 2023
  3. Primary completion31 Dec 2029 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
141 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06975618
Sponsor's protocol ID
CYH33-G208
Status last verified
Jun 2026
First submitted
28 Apr 2025
Last updated
29 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CYH33 in people with PIK3CA-Related Overgrowth Spectrum (PROS) and PIK3CA-related Vascular Malformations (PRVM), run by Haihe Biopharma Co., Ltd. at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in China, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xiaoxi Lin, MD (+86-13701997136, linxiaoxi@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: The maximum tolerated dose (MTD) and/or phase II recommended dose (RP2D) (time frame: 27 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06975618.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.

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