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

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Venthera, Inc.; Venthera, Inc., a BridgeBio company

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