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

NCT04409145 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: VT30-101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 15

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.

Conditions

Venous Malformation; Lymphatic Malformation; Venolymphatic Malformation

Outcome Measures

Primary Outcomes (1)

• Evaluation of safety and tolerability

  Composite of adverse events and changes in physical exam findings, vital signs, lab tests, and electrocardiogram evaluations

  From pre-treatment to 4 weeks of treatment

Secondary Outcomes (2)

• Maximum feasible dose / maximum tolerable dose

  From pre-treatment to 4 weeks

• Tissue and serum drug levels

  From pre-treatment to 4 weeks

Other Outcomes (4)

• Maximum tissue concentration of study drug

  From pre-treatment to 4 weeks

• Changes in Pain

  From pre-treatment to 4 weeks

• Changes in lesion

  From pre-treatment to 4 weeks

Study Arms (1)

VT30

EXPERIMENTAL

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

Interventions

VT30 DRUG

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.

VT30

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Venthera, Inc., a BridgeBio company: lead

Study Sites (15)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital/UAMS

Little Rock, Arkansas, 72202, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Dermatology Cosmetic Laser Medical Associates of La Jolla

San Diego, California, 92121, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Indiana University Health (Riley Children's Hospital and University Hospital)

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University

Raleigh, North Carolina, 27513, United States

Location

Cincinnatti Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University Hospitals- Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

University of Virginia Department of Dermatology

Charlottesville, Virginia, 44106, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53715, United States

Location

MeSH Terms

Conditions

Lymphatic Abnormalities

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Michael Henderson

  Venthera, Inc., a BridgeBio company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Part 1: Open label Part 2: Double blind
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: June 1, 2020
• Study Start: October 1, 2020
• Primary Completion: April 13, 2022
• Study Completion: April 13, 2022
• Last Updated: August 4, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)