Effect of Ev.FV on Wound Healing in Dystrophic Epidermolysis Bullosa

Safety and Efficacy of Ev.FV in Epidermolysis Bullosa Patients, A Randomized Clinical Trial, Phase 1 , 2

Epidermolysis bullosa (EB) is a hereditary disease of skin tissues that causes painful bleeding blisters in the skin and mucous membrane. The prevalence of this disease is 1 in 50,000. The severity of the disease varies depending on the type of disease and may even lead to death. This disease is caused by a genetic mutation in keratin or collagen, and its incidence is the same in all men and women of different human races. In these patients, the skin becomes extremely fragile and peels off with the slightest scratch. Many blisters are one of the most obvious symptoms of this disease. The possibility of skin cancer in people suffering from this disease is more than others.

Nowadays, the preference of cell therapy methods is to use biological products produced by cells such as extracellular vesicles and mitochondria instead of stem cells. The use of Extracellular vesicles and engineered EVs as messenger carriers can introduce a new treatment method based on cell products for skin regeneration and as an alternative to cell therapy.

Therefore, in this study, EV.FV will be applied topically to patients.

Study Overview

• Status: Recruiting
• Conditions: Wound Heal; Dystrophic Epidermolysis Bullosa
• Intervention / Treatment: Biological: Ev.FV 1.0 x 1011 par/ml

Detailed Description

Mesenchymal stem cell-derived EV which included Five Factors act as cell-free nanovesicles that mediate intercellular communication by transferring functional biomolecules including mRNA, microRNA, proteins, and lipids to recipient skin cells. In dystrophic epidermolysis bullosa, these exosomes facilitate wound repair and regeneration through several mechanisms: (1) modulation of inflammation by down-regulating pro-inflammatory cytokines; (2) stimulation of fibroblast and keratinocyte proliferation and migration; (3) promotion of angiogenesis via vascular endothelial growth factor (VEGF) signaling; and (4) potential delivery of collagen VII related proteins and mRNAs that support dermal epidermal junction repair. Thus, the therapeutic benefit of exosome therapy arises from paracrine signaling and molecular cargo transfer rather than cell engraftment, providing a safer and more controlled alternative to live stem cell transplantation.

Our study focused on dystrophic EB (DEB), the most severe form, where loss of collagen VII disrupts anchoring fibrils and dermal-epidermal adhesion. This pathology makes DEB an appropriate target for regenerative therapies such as mesenchymal stem cell-derived EVs and investigates if EVs from MSCs are safe and effective for treating DEB. It will examine how well these exosomes help heal wounds and promote tissue regeneration, hoping to find a new biological treatment option for this challenging disease.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Leila Dehghani, Dr; Phone Number: 031 36202020; Email: l_dehghani2002@yahoo.com
• Study Contact Backup: Name: Masoud Soleimani, Prof; Phone Number: 031 03136202020; Email: soleimani.masoud@gmail.com

Study Locations

• Iran
  • Isfahan, Iran
    • Recruiting
    • Alzahra Hospital
    • Contact: Leila Dehghani, Prof; Phone Number: 031 36202020; Email: l_dehghani2002@yahoo.com
    • Contact: Masoud Soleimani, Prof; Phone Number: 031 36202020; Email: soleimani.masoud@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• DEB participants determined by electron microscopy, or genetic testing. Individuals with severe DEB (eg, RDEB patients with an absence of collagen VII) and milder forms of DEB (eg, RDEB patients with reduced levels of collagen VII) will be eligible.
• People with one or more active wounds (each between 10 and 50 square centimeters on the arms, legs or trunk.)
• Participants must be willing to comply with the requirements of the protocol and have consent to participate in the project.
• Participants must be negative in the urine drug screening visit.

Exclusion Criteria:

• Participants with clinical evidence of systemic infection.
• Participants have a history of bone marrow transplantation.
• Participants must have evidence of autoimmune disease, including insulin-dependent diabetes.
• Participant has evidence of significant wound healing prior to treatment (ie, wound closure ≥ 20% during treatment at the first observation period).
• Participant has a severe medical condition, such as malignancy (including skin cancer), life expectancy less than 2 years, which limits movement to the clinical center.
• Participants have a current history of alcohol or substance abuse or a history of alcohol or substance abuse that requires treatment in the past 12 months.
• People participating in the screening should have a positive hepatitis and human immunodeficiency virus (HIV) test result.
• Women who are pregnant, lactating or planning to become pregnant during the study
• Women who are of reproductive age and use birth control pills.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Qualified patients who have confirmed chronic wounds (10-50cm2) are included in the study after completing the consent form	Biological: Ev.FV 1.0 x 1011 par/ml; Ev.FV 1.0 x 1011 par/ml, IV, Total of 6 doses every 2weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of wound closure	percentage reduction in wound area compared to baseline, assessed by digital planimetry	Day 14
EBDASI	EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score,	Day 14, 28, month 3 and month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain score (VAS Scale)	Change in pain intensity at the wound site measured using VAS Questionnaire	30 days

Collaborators and Investigators

• Sponsor: Isfahan University of Medical Sciences
• Investigators: Study Director: Masoud Soleimani, Prof, Shahid Beheshti University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 25, 2026

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Connective Tissue Diseases; Skin Diseases; Congenital Abnormalities; Skin Diseases, Genetic; Skin Abnormalities; Skin Diseases, Vesiculobullous; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica
• Other Study ID Numbers: shahid beheshti UMS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No