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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
Sponsor:
Information provided by (Responsible Party):
Venthera, Inc.

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: N/A
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
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: VT30
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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  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


Other Outcome Measures:
  1. 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

  2. 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

  3. Changes in lesion [ Time Frame: From pre-treatment to 4 weeks ]
    Assessed by change in appearance of the treated lesion

  4. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have signed the current approved informed consent form
  2. Have a clinically or phenotypically defined VM, LM, or mixed VLM affecting the skin
  3. Lesion genotyping confirms either PIK3CA or TEK mutations, known to be pathogenic
  4. Agrees to use contraception if of childbearing potential
  5. Be willing and able to comply with the protocol and be available for the entire study
  6. Be at least 18 to 60 years of age
  7. Lesion must be amenable to defining a contiguous study treatment area of 140 cm2

Exclusion Criteria:

  1. Lesion to be treated is on the face or involves mucosa
  2. Presence of ulcerations on the target-treatment lesion
  3. Known systemic hypersensitivity to the VT30 drug substance, its inactive ingredients, or the vehicle
  4. Uncontrolled diabetes mellitus
  5. Hyperlipidemia that is poorly controlled on current treatment
  6. Pregnant or nursing, planning to become pregnant, or planning to father a child during the study
  7. History of malignancy except successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix
  8. 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
  9. 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
  10. Medically significant infection (eg, cellulitis or abscess, or a systemic infection) within 8 weeks of Screening
  11. 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
  12. Use of a biologic or systemic immunosuppressive agent within 3 months of Screening
  13. Systemic use of corticosteroids, within 30 days of Screening
  14. Treatment with a small molecule investigational product within 30 days of Screening, or with any investigational biologic products within 3 months of Screening
  15. Positive for hepatitis C antibody, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
  16. Alanine transaminase or aspartate transaminase laboratory values in excess of 1.5X the upper limit of normal at Screening
  17. Hemoglobin A1c is >8%
  18. 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
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Responsible Party: Venthera, Inc.
ClinicalTrials.gov Identifier: NCT04409145    
Other Study ID Numbers: VT30-101
First Posted: June 1, 2020    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphangioma
Lymphatic Abnormalities
Congenital Abnormalities
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases