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History of Changes for Study: NCT04409145
First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations
Latest version (submitted August 1, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 26, 2020 None (earliest Version on record)
2 October 2, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 October 29, 2020 Contacts/Locations and Study Status
4 November 23, 2020 Study Status and Contacts/Locations
5 December 15, 2020 Contacts/Locations and Study Status
6 December 15, 2020 Contacts/Locations and Study Status
7 March 29, 2021 Contacts/Locations and Study Status
8 April 30, 2021 Contacts/Locations and Study Status
9 July 8, 2021 Study Status and Contacts/Locations
10 August 26, 2021 Study Status
11 August 1, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
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Study NCT04409145
Submitted Date:  May 26, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: VT30-101
Brief Title: First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations
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
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2020
Overall Status: Not yet recruiting
Study Start: September 2020
Primary Completion: June 2022 [Anticipated]
Study Completion: June 2022 [Anticipated]
First Submitted: May 11, 2020
First Submitted that
Met QC Criteria:
May 26, 2020
First Posted: June 1, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
May 26, 2020
Last Update Posted: June 1, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Venthera, Inc., a BridgeBio company
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.

Detailed Description:

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)

A Safety Review Committee (SRC), with sponsor, investigator and independent medical representation, will provide oversight and guidance for study conduct. After 3 subjects have been dosed for at least 21 days in any of the first three Part 1 cohorts, the SRC may request additional data, approve initiation of the subsequent cohort, or mandate that additional subjects to be enrolled at either the higher or lower dose within the cohort.

After 9 subjects in Cohorts 1 through 3 (3 subjects per cohort) have completed the 4-week Treatment Period, the SRC will determine if additional subjects should be assigned to Cohort 4 (or the final Part 1 cohort) to receive the MTD (maximum tolerated dose) or MFD (maximum feasible dose) strength of VT30. Subjects in Cohort 4 will receive the designated dose strength and regimen of VT30 for a full 4 weeks.

Following the completion of Cohort 4 in Part 1, the SRC will determine whether to authorize initiation of Part 2 and will confirm the dose level and regimen to be administered in Part 2.

Part 2 will be a randomized, placebo-controlled, double-blind study containing 36 subjects assigned in a 2:1 ratio to receive either VT30 or placebo. Up to 12 subjects who complete Part 1 may enroll in Part 2, provided they meet all Part 2-specific inclusion criteria with no applicable exclusions.

After the first 12 subjects in Part 2 have completed 4 weeks of treatment, the SRC will conduct a review of blinded safety data to confirm no revisions or changes are needed to the protocol. Subsequent reviews may also be conducted to ensure continued acceptable safety and tolerability.

After subjects complete their designated Treatment Period (in Part 1 or Part 2), they will participate in a 4-week post treatment Follow-up Period.

Open or close this module Conditions
Conditions: Venous Malformation
Lymphatic Malformation
Venolymphatic Malformation
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Single Group Assignment
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
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 51 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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.
Open or close this module Outcome Measures
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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 60 Years
Sex: All
Gender Based:
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
Open or close this module Contacts/Locations
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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