IRB Study Number 25-424
Status Recruiting
Phase Phase 2
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Safety Objectives
The safety objective of this study is to evaluate the safety of once-daily PTX-022 in study participants with a cutaneous venous malformation.
Efficacy Objectives
The efficacy objectives of this study include determining the efficacy of once-daily treatment with PTX-022 for the treatment of cVM using the:
• Overall cutaneous venous malformation Investigator Global Assessment (cVM-IGA)
• Cutaneous venous malformation Investigator Global Assessment (cVM-IGA) for height/engorgement, appearance, bleeding, and ulceration
• Scores from the cutaneous venous malformations Multicomponent Static Scale (cVM -MCSS)
• Overall Patient Global Impression of Change (PGI-C)
• Overall Clinician Global Impression of Severity (CGI-S)
• Clinician Global Impression of Severity (CGI-S) for bleeding
• Clinician Global Impression of Severity (CGI-S) for ulceration
• Overall Patient Global Impression of Severity (PGI-S)
Inclusion Criteria
1) The participant must be ≥6 years of age at consent (and assent if legally able).
2) The participant must have a clinically confirmed superficial/ cutaneous (visible on the skin) venous malformation (cVM).
3) Participants must have a total combined area of cVMs between 9 cm2 and 400 cm2 referred to as the “total treatment area”.
4) For cVMs with a total treatment area of 200cm2 the total treatment area will be evaluated for safety and efficacy and be synonymous with the “efficacy evaluation area”. For cVMs with a total treatment area > 200cm2 a cVM of approximately 200cm2 will be selected within the total treatment area for efficacy evaluation (referred to as “efficacy evaluation area”). In all cases the total treatment area will be evaluated for safety.
5) Via in-person skin examination, the investigator must identify that the cVM identified as the efficacy evaluation area:
a. is primarily a shade of blue or purple in color.
b. is ≥ moderate on the overall CGI-S severity scale as rated during live assessment by the clinician.
c. contains no, or a minority (<30%), lymphatic component (mixed venous / lymphatic malformation) in the efficacy evaluation area.
6) The participant’s efficacy evaluation area is ≥ moderate on the overall PGI-S severity scale. For pediatric participants age 6 to less than 12 years old, the caregiver PGI-S will be used for eligibility.
7) At least 14 days have elapsed since the participant completed therapy with a Growth Factor (GF) that supports platelet, red or white cell number or function.
8) At least 4 weeks has elapsed since the participant has received investigational drug or biologic (4 weeks or 5 half-lives, whichever is longer), prior to starting treatment with and during treatment with PTX-022.
9) At least 5 months has elapsed since the participant received field radiation (XRT) administered to the cutaneous venous malformation treatment area.
10) The participant is willing to abstain from application of other prescription or over the counter topical medications in the treatment area during the treatment period. Moisturizers and emollients are allowed.
11) The participant is willing to forego medical interventional treatment (i.e., topical or systemic pharmacological treatment or interventions such as sclerotherapy) of their cutaneous venous malformation with anything other than the study drug during the study except when the Investigator believes that delay of treatment potentially might compromise the health of the participant.
12) For participants aged >6 years to <12 years old, a consistent caregiver must complete the participant assessments throughout the study.
Exclusion Criteria
1) The participant has previously participated in a clinical trial evaluating PTX-022.
2) The participant’s total treatment area is mainly in any wet mucosa or within the orbital rim. For clarification, no part of the venous malformation should be evaluated or treated if it is in mucosa. External genital presentation is permitted.
3) The participant has a known pervasive extension of the cVM into mucosa, bone or tissue (as determined by diagnostic or the investigator) that would impair the ability of the investigator to evaluate the cutaneous components of the venous malformation.
4) The participant has active ulcer in the total treatment area that is >~25% of the efficacy evaluation area.
5) The participant has been diagnosed with PIK3CA-related overgrowth spectrum (PROS).
6) Participants who are pregnant, breastfeeding or planning to become pregnant during the
study including through the follow-up period.
7) Participants of childbearing potential who are unwilling or unable to comply with
contraception measures (see Section 4.1).
8) The participant has any condition or situation which, in the Investigator's opinion, may
put the participant at significant risk, could confound the study results, or could interfere
significantly with the participant's participation in the study.
9) Participants deemed by the investigator as unwilling or unable to remain compliant with
all tests and procedures, adherence to the study drug administration regimen and other
protocol-required activities.
10) The participant has used oral or topical sirolimus, an mTOR inhibitor, or a PI3K inhibitor
in the past 6 months.
11) The participant has had photodynamic therapy (PDT), sclerotherapy, venous ablation,
laser procedures, or other surgeries to the cutaneous venous malformation identified for
the study within 3 months.
12) No intercurrent serious infection.
13) Participant has a known hypersensitivity to sirolimus.
14) Participant reports they are HIV seropositive or has another known immunodeficiency.
15) Complicated vascular anomalies with severe symptoms that require systemic therapy.
16) Interpretable/ high quality photographs of the treatment area are unable to be obtained.
Docusign Envelope ID: B16D23C1-9994-4FF8-90AF-AE233476F110
