First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations
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|ClinicalTrials.gov Identifier: NCT04409145|
Recruitment Status : Not yet recruiting
First Posted : June 1, 2020
Last Update Posted : June 1, 2020
VT30-101 is a 2-part first-in-human trial of topically administered VT30 to subjects with cutaneous venous malformations, lymphatic malformations, or mixed venolymphatic malformations associated with PIK3CA or TEK mutations.
Part 1 is a 4-week treatment, open-label, 4-sequence, escalating repeat-application cohort study, with intra-subject and inter-cohort dose escalation.
Part 2 is a 12-week treatment, randomized, placebo-controlled, double-blind, safety and exploratory efficacy study. Part 2 will be initiated only after the successful completion of Part 1 with results that demonstrate the general safety and tolerability of topically applied VT30. Up to 12 subjects who complete Part 1 may be enrolled into Part 2 of the study.
The primary objective is to evaluate the safety and tolerability of VT30. The study will also determine the dose and regimen of VT30 to be carried into Part 2 of the protocol. Other aims include documenting plasma drug levels of VT30 and VT10 and, on an exploratory basis, examining pharmacologic target engagement and change in potential efficacy readouts.
|Condition or disease||Intervention/treatment||Phase|
|Venous Malformation Lymphatic Malformation Venolymphatic Malformation||Drug: VT30||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||51 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Part 1: Open-label, 4-sequence, escalating repeat-application cohort study, with intra-subject and inter-cohort dose escalation to determine safety and tolerability, and maximum feasible dose/maximum tolerable dose Part 2: Randomized, placebo-controlled, double-blind, safety and exploratory efficacy study|
|Masking:||None (Open Label)|
|Masking Description:||Part 1: Open label Part 2: Double blind|
|Official Title:||Open-Label, Intra Subject, Dose Escalation (Part 1) Followed by Randomized, Double Blind, Placebo Controlled (Part 2) Trial of Topical VT30 in Pts With Venous, Lymphatic or Mixed Malformations Associated With PIK3CA or TEK Genetic Mutations|
|Estimated Study Start Date :||September 2020|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||June 2022|
VT30 is a PI3K-inhibitor prodrug, formulated as a topical gel and dispensed from a metered dose pump; administration is once or twice daily, applied to target-treatment area(s) on the skin. One pump action dispenses 250 µL of gel, intended to treat an area of 140 cm2.
VT30 gel is intended as a topical treatment of cutaneous VMs, LMs, or VLMs that driven by inappropriate PI3K activation. In the skin, VT30 is rapidly metabolized to VT10, an active drug form, and is intended to sufficiently permeate the stratum corneum and achieve target engagement. It is expected that VT30 will lead to amelioration of the signs and symptoms of cutaneous VMs, LMs and/or VLMs.
- Evaluation of safety and tolerability [ Time Frame: From pre-treatment to 4 weeks of treatment ]Composite of adverse events and changes in physical exam findings, vital signs, lab tests, and electrocardiogram evaluations
- Maximum feasible dose / maximum tolerable dose [ Time Frame: From pre-treatment to 4 weeks ]The MTD or MFD strength will be determined based on results from Part 1, and will inform the dose strength to be used in Part 2
- Tissue and serum drug levels [ Time Frame: From pre-treatment to 4 weeks ]Plasma levels of VT30 and VT10 will be assessed following topical administration of VT30 to determine level of systemic exposure
- Maximum tissue concentration of study drug [ Time Frame: From pre-treatment to 4 weeks ]As assessed by treated lesion tissue levels of phosphoproteins, as an indicator of local target engagement
- Changes in Pain [ Time Frame: From pre-treatment to 4 weeks ]Assessed by subjects' self-reporting their pain, related to the treated lesion, on a Numerical Rating Scale
- Changes in lesion [ Time Frame: From pre-treatment to 4 weeks ]Assessed by change in appearance of the treated lesion
- Changes in management of lesion bleeding, oozing, or discharge [ Time Frame: From pre-treatment to 4 weeks ]Assessed by subject-reported difficulty managing bleeding, oozing, or discharge from the treated lesion