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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 15
- 试验地点
- 15
- 主要终点
- Evaluation of safety and tolerability
研究概览
简要总结
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.
详细描述
VT30-101 is designed as a Phase 1/2, first-in-human study of topically administered VT30 to subjects with cutaneous venous malformations (VMs), lymphatic malformations (LMs), or mixed venolymphatic malformations (VLMs) associated with phosphatidylinositol 3-kinase catalytic alpha polypeptide (PIK3CA) or tyrosine receptor kinase (TEK) mutations. Capillary involvement and/or extension of the lesion into subcutaneous tissues is permitted.
The study will occur in 2 parts, and in both study parts, subjects will participate in a Screening Period (up to 6 weeks) before beginning the indicated Treatment Period.
Part 1 will be an open-label, 4-sequence, escalating repeat-application study comprised of up to 4 cohorts (3 subjects per cohort, with 3 up to 6 in Cohort 4, or the final Part 1 cohort). In each cohort, subjects will be given topical VT30 for a 4-week Treatment Period. Subjects will begin treatment with the designated dose on Day 1. After 2 weeks, the Investigator will examine the treated surface area and determine if the formulation is tolerated such that the subject may apply the next dose strength of VT30 gel for the remaining duration of the Treatment Period.
Specifically, the following gel dose strengths (concentrations) are planned for Cohorts 1 through 3 in Part 1:
- Cohort 1: initiate dosing with 0.12% (w/w) gel and progress to 0.6% (w/w) gel for the final 2 weeks of the Part 1 Treatment Period (if the lower dose is tolerated)
- Cohort 2: initiate dosing with 0.6% (w/w) gel and progress to 1.2% (w/w) gel for the final 2 weeks of the Part 1 Treatment Period (if the lower dose is tolerated)
- Cohort 3: initiate dosing with 1.2% (w/w) gel and progress to 2.3% (w/w) gel for the final 2 weeks of the Part 1 Treatment Period (if the lower dose is tolerated)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Part 1: Open label Part 2: Double blind
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have signed the current approved informed consent form
- •Have a clinically or phenotypically defined VM, LM, or mixed VLM affecting the skin
- •Lesion genotyping confirms either PIK3CA or TEK mutations, known to be pathogenic
- •Agrees to use contraception if of childbearing potential
- •Be willing and able to comply with the protocol and be available for the entire study
- •Be at least 18 to 60 years of age
- •Lesion must be amenable to defining a contiguous study treatment area of 140 cm2
排除标准
- •Lesion to be treated is on the face or involves mucosa
- •Presence of ulcerations on the target-treatment lesion
- •Known systemic hypersensitivity to the VT30 drug substance, its inactive ingredients, or the vehicle
- •Uncontrolled diabetes mellitus
- •Hyperlipidemia that is poorly controlled on current treatment
- •Pregnant or nursing, planning to become pregnant, or planning to father a child during the study
- •History of malignancy except successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix
- •Major surgery within 8 weeks of Screening, or a surgical, laser or other procedure involving the target lesion within 8 weeks of Screening, or planned to occur during the study
- •Any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the subject, or may preclude the subject's successful completion of the clinical study
- •Medically significant infection (eg, cellulitis or abscess, or a systemic infection) within 8 weeks of Screening
- •Ongoing therapy with another topical treatment or any medication that inhibits PI3K, Akt pathway, or the mTOR pathway, or in the opinion of the Investigator, the subject requires systemic therapy for their vascular malformation condition
- •Use of a biologic or systemic immunosuppressive agent within 3 months of Screening
- •Systemic use of corticosteroids, within 30 days of Screening
- •Treatment with a small molecule investigational product within 30 days of Screening, or with any investigational biologic products within 3 months of Screening
- •Positive for hepatitis C antibody, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
- •Alanine transaminase or aspartate transaminase laboratory values in excess of 1.5X the upper limit of normal at Screening
- •Hemoglobin A1c is >8%
- •Any other clinically significant laboratory or testing abnormality that, in the opinion of the Investigator, might confound the study, interfere with the subject's ability to complete the study, or represent a meaningful safety risk upon study enrollment
研究组 & 干预措施
VT30
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.
干预措施: VT30 (Drug)
结局指标
主要结局
Evaluation of safety and tolerability
时间窗: 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
次要结局
- Maximum feasible dose / maximum tolerable dose(From pre-treatment to 4 weeks)
- Tissue and serum drug levels(From pre-treatment to 4 weeks)