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First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04409145
Recruitment Status : Terminated (Part 1 complete; Part 2 will not be completed.)
First Posted : June 1, 2020
Last Update Posted : August 4, 2022
Sponsor:
Information provided by (Responsible Party):
Venthera, Inc., a BridgeBio company

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)
Actual Enrollment : 15 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
Actual Study Start Date : October 1, 2020
Actual Primary Completion Date : April 13, 2022
Actual Study Completion Date : April 13, 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



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04409145


Locations
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United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, Arkansas
Arkansas Children's Hospital/UAMS
Little Rock, Arkansas, United States, 72202
United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94304
Dermatology Cosmetic Laser Medical Associates of La Jolla
San Diego, California, United States, 92121
United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, Indiana
Indiana University Health (Riley Children's Hospital and University Hospital)
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University
Raleigh, North Carolina, United States, 27513
United States, Ohio
Cincinnatti Children's Hospital
Cincinnati, Ohio, United States, 45229
University Hospitals- Cleveland Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Texas Dermatology and Laser Specialists
San Antonio, Texas, United States, 78218
United States, Virginia
University of Virginia Department of Dermatology
Charlottesville, Virginia, United States, 44106
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53715
Sponsors and Collaborators
Venthera, Inc., a BridgeBio company
Investigators
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Study Director: Michael Henderson Venthera, Inc., a BridgeBio company
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Responsible Party: Venthera, Inc., a BridgeBio company
ClinicalTrials.gov Identifier: NCT04409145    
Other Study ID Numbers: VT30-101
First Posted: June 1, 2020    Key Record Dates
Last Update Posted: August 4, 2022
Last Verified: August 2022
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