MSC EVs in Dystrophic Epidermolysis Bullosa

Related Clinical Trial
Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of Epidermolysis Bullosa (Phase III, Cross-over) Growth Hormone in EB Dose-ranging Study of Dentoxol® Mouthrinse for Managing Oral Symptoms in People With Epidermolysis Bullosa. Study to Evaluate Safety and Efficacy of ALLO-ASC-SHEET in Subjects With Dystrophic Epidermolysis Bullosa Extension Study to PTR-01-002 Long-Term Follow-up Protocol A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa Improve Adherence to Weak or Strong Opioid Analgesics at the Time of Care in Children With Hereditary Epidermolysis Bullosa Gynecological Follow-up of Patients With Dystrophic Epidermolysis Bullosa (EBD) Topical Gentamicin Nonsense Suppression Therapy of EB The Efficacy and Safety of 3% Cannabidiol (CBD) Cream in Patients With Epidermolysis Bullosa: A Phase II/III Trial A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa Safety and Effectiveness Study of Allogeneic Umbilical Cord Blood-derived Mesenchymal Stem Cell in Patients With RDEB The Objective of This Study is to Compare the Efficacy and Safety of Beremagene Geperpavec (B-VEC) Topical Gel With That of Placebo for the Treatment of Dystrophic Epidermolysis Bullosa (DEB). Trial To Assess Efficacy Of A Chimeric Skin In Patients With Epidermolysys Bullosa Randomised Double Blind Placebo Controlled Cross Over Design of the Efficacy of Topical Morphine for Inflammatory Pain in Children With Epidermolysis Bullosa Study of Cellutome System for Treatment of Individual Lesions in EB Pts Neurokinin-1 Receptor Antagonist for the Treatment of Itch in EB Patients A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa Biochemical Correction of Severe EB by Allo HSCT and “Off-the-shelf” MSCs Survey to Identify Burdens and Unmet Needs of Patients With Epidermolysis Bullosa Study of the Nutritional, Metabolic, and Body Composition Profile in Children and Adolescents With Epidermolysis Bullosa MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs Randomised Double Blind Crossover Placebo Controlled Study to Evaluate the Efficacy of Tetracycline in Epidermolysis Bullosa Observational Study of a Cohort of Patients With Hereditary Epidermolysis Bullosa Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa A Observational Study to Evaluate Apligraf(R) in Nonhealing Wounds of Subjects With Epidermolysis Bullosa Study of Effectiveness and Safety of SD-101 in Participants With Epidermolysis Bullosa Open Label Extension Study to Evaluate the Long-term Safety of Zorblisa (SD-101-6.0) in Patients With Epidermolysis Bullosa Open-Label Extension Study to Evaluate the Safety of SD-101 Cream in Participants With Epidermolysis Bullosa ESSENCE Study: Efficacy and Safety of SD-101 Cream in Participants With Epidermolysis Bullosa Grafting of Epidermolysis Bullosa Wounds Using Cultured Revertant Autologous Keratinocytes Topical BPM31510 3.0% Cream in Patients With Epidermolysis Bullosa Evaluation of the Efficacy of ROPIVACAINE in Children and Young Adults With Hereditary Epidermolysis Bullosa Oleogel-S10 in Wound Healing of Inherited Epidermolysis Bullosa (BEB-10) The Efficacy of Trimethoprim in Wound Healing of Patients With Epidermolysis Bullosa A Phase 2 Study on Effect of Thymosin Beta 4 on Wound Healing in Patients With Epidermolysis Bullosa A Follow-up Study to Evaluate the Efficacy and Safety of ALLO-ASC-DFU in ALLO-ASC-EB-101 Clinical Trial Proof of Concept Study for a Dressing Glove Pregabalin Treatment for RDEB Pain and Itch Study of Alwextin® Cream in Treating Epidermolysis Bullosa A Study of the Efficacy and Safety of ABH001 in the Treatment of Patients With Epidermolysis Bullosa Who Have Wounds That Are Not Healing Uses of Irradiated Human Amniotic Membrane in the Treatment of Dystrophic Epidermolysis Bullosa Patients Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa A Comparative Study of the Healing of Chronic Ulcers of Recessive Epidermolysis Bullosa : Dressing vs Amniotic Membrane Topical QR-313 in Dominant Dystrophic Epidermolysis Bullosa (DDEB) or Recessive Dystrophic Epidermolysis Bullosa (RDEB) Due to Mutation(s) in Exon 73 of the COL7A1gene Rigosertib for RDEB-SCC Phase I Study of Isotretinoin in Patients With Recessive Dystrophic Epidermolysis Bullosa Short Term Observational Study in DEB Patients Gentamicin for RDEB Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With RDEB. Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients Self-Assembled Skin Substitute for the Treatment of Epidermolysis Bullosa Allogeneic Stem Cell Transplantation (ALLOSCT) in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa Topical Beremagene Geperpavec (KB103) Gene Therapy to Restore Functional Collagen VII for the Treatment of Dystrophic Epidermolysis Bullosa A Study of FCX-007 for Recessive Dystrophic Epidermolysis Bullosa (RDEB) A Phase 1/2 Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Molecular Signatures of Cutaneous Squamous Cell Carcinoma During Recessive Dystrophic Epidermolysis Bullosa Treatment of Chronic and Non-Chronic Wounds in Patients With Recessive Dystrophic Epidermolysis Bullosa Using Helicoll Collagen Dressings Versus Standard of Care Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) MSC EVs in Dystrophic Epidermolysis Bullosa Mesenchymal Stromal Cells in Adults With Recessive Dystrophic Epidermolysis Bullosa Prospective, Longitudinal Natural History Study in Dystrophic Epidermolysis Bullosa Recessive Dystrophic Epidermolysis Bullosa Screening for Possible Gene Transfer Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC Treatment of Epidermolysis Bullosa Dystrophica by Polyphenon E (Epigallocatechin 3 Gallate) Characteristics of Adult Patients With Recessive Dystrophic Epidermolysis Bullosa Efficacy of Granulocyte Colony Stimulating Factor (GCSF) In Patients With Dystrophic Epidermolysis Bullosa Characteristics of Patients With Recessive Dystrophic Epidermolysis Bullosa Study to Evaluate the Safety of ALLO-ASC-DFU in the Subjects With Dystrophic Epidermolysis Bullosa The Natural History of Wounds in Patients With Dystrophic Epidermolysis Bullosa (DEB) A Study of FCX-007 for Recessive Dystrophic Epidermolysis Bullosa A Pilot Study of HP802-247 in Dystrophic Epidermolysis Bullosa

Brief Title

MSC EVs in Dystrophic Epidermolysis Bullosa

Official Title

A Safety Study of the Administration of Mesenchymal Stem Cell Extracellular Vesicles in the Treatment of Dystrophic Epidermolysis Bullosa Wounds

Brief Summary

      INVESTIGATIONAL PRODUCT: AGLE-102 is an allogeneic derived extracellular vesicle (EV) product
      derived from normal donor mesenchymal stem cells (MSCs).

      INDICATION AND RATIONALE: The aim of the study is to assess the safety and efficacy of
      AGLE-102 in the treatment of lesions in subjects with Epidermolysis Bullosa (EB).

      STUDY DESIGN: This is a phase 1/2A, non randomized, multi-center, ascending dose, study to
      assess the effectiveness and safety of AGLE-102 on lesions in subjects with EB.
    

Detailed Description

      STUDY DESIGN: This is a phase 1/2A, non randomized, multi-center, ascending dose, study to
      assess the effectiveness and safety of AGLE-102 on lesions in subjects with EB.

      Eligible subjects will undergo a one-month observation period to confirm that the targeted
      wound is chronic (only single wounds with evidence of less than 20% closure over that period
      will be eligible for treatment). Once this has been established, up to 6 administrations of
      BM-MSC EVs will occur, at each to be given over a period of no more than 3 months. A maximum
      of 50 cm2 in total wound surface will be treated, and each administration will occur 14 days
      (+/- 7 days) but no less than 7 days apart. If the wound closes prior to 6 administrations,
      no additional doses will be given. Wound closure will be determined by complete
      re-epithelialization that is not subject to re-injury during dressing changes or as a result
      of normal daily activities (e.g. wearing clothing, eating, sleeping). After the 6 doses of
      BM-MSC EVs are given, the wound will be followed monthly for a period of 4 months to the
      termination of the study at 8 months or, in the event the wound closes before receiving all 6
      doses, for 4 month after the wound closes. The ARANZ SilhouetteStarTM will be used to measure
      the target lesion at all visits.

      STUDY OBJECTIVES:

      Primary Objective: The primary objective is to determine the safety of applying single
      administrations of 2 ascending dose levels of EVs derived from allogeneic MSCs to DEB wounds
      between 10 and 50 cm2 that have persisted for more than one month

      Secondary Objectives: The secondary objectives are to determine the safety of applying
      multiple administrations of 2 ascending dose levels of EVs derived from allogeneic MSCs to
      DEB wounds between 10 and 50 cm2 that have persisted for more than one month and to determine
      if there is clinical benefit (>50% closure) of applying BM-MSC EVs to DEB wounds

      PLANNED SAMPLE SIZE: 10 subjects will be treated on the protocol with AGLE-102.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Dose Limiting Toxicity

Secondary Outcome

 Wound size evaluation

Condition

Dystrophic Epidermolysis Bullosa

Intervention

AGLE 102

Study Arms / Comparison Groups

 AGLE 102
Description:  Treatment arm

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

October 2023

Completion Date

January 2025

Primary Completion Date

July 2024

Eligibility Criteria

        Inclusion Criteria:

          1. The first 2 subjects must be 18 years or older at the time of signing the informed
             consent. If approved by the SRC, additional subjects (after the first 2 subjects) may
             be 6 years or older at the time of signing the informed consent; otherwise additional
             subjects must be 18 years or older until such time it is considered by the SRC as
             appropriate to lower the age limit to 6 years.

          2. Subjects who have a confirmed diagnosis of DEB as determined by electron microscopy,
             immunomapping, or genetic testing. Subjects with severe DEB (e.g., RDEB patients with
             absent Col VII/no anchoring fibrils) and milder forms of DEB (e.g., RDEB patients with
             reduced Col VII and/or anchoring fibril levels) will be eligible.

          3. Subjects who have one or more active wounds (unroofed EB erosions) each between 10 and
             50 cm2 on arms, legs, or trunk.

          4. Females of childbearing potential must have a negative urine or serum pregnancy test
             at screening and agree to continue use of an acceptable form of birth control
             throughout the duration of the study. Acceptable forms of birth control include oral,
             implant, injectable, and transdermal contraceptives; an intrauterine device; or other
             forms considered acceptable by the investigator.

          5. Subjects or guardian of subjects who are under the age of 18 years must be capable of
             giving signed informed consent as described in Appendix 1, which includes compliance
             with the requirements and restrictions listed in the informed consent form (ICF) and
             in this protocol.

          6. Subjects must be willing to comply with the protocol requirements.

          7. Subjects must be accessible for wound treatments and assessment visits.

          8. Subjects must have a negative urine test for drugs of abuse at the screening visit.

          9. Female subjects willing to minimize the risk of inducing pregnancy for the duration of
             the clinical study and follow-up period.

         10. A female subject is eligible to participate if she is not pregnant (i.e. has a
             negative urine pregnancy result at the Screening Visit and on Day 1), and at least one
             of the following conditions applies:

         11. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3

         12. Or a WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
             intervention and follow-up period

        Note: Reference to Appendix 3 can be located in the protocol

        Exclusion Criteria:

          1. The subject has clinical evidence of systemic infection.

          2. The subject has a history or bone marrow transplantation.

          3. The subject has evidence of autoimmune disease, including insulin-dependent diabetes.

          4. The subject has wounds that are considered by the investigator as likely to heal
             within 1 month after standard therapy.

          5. The subject has clinical evidence of an active infection at the wound site.

          6. The subject has evidence of significant wound healing before treatment (i.e., ≥ 20%
             closure of wound during the first month observation period treatment).

          7. The subject has a wound that extends across the fingers, toes, pubic or perineum
             region.

          8. The subject has a severe medical condition, such as malignancy (including skin
             cancer), a life expectancy of < 2 years, or severe cardiopulmonary disease that
             restricts ambulation to the clinical facility.

          9. The subject has a history of coagulopathy.

         10. The subject currently uses systemic steroids or immunosuppressive agents.

         11. The subject is allergic to human albumin, streptomycin, or penicillin.

         12. The subject is a potential recipient of tissue or organ transplantation.

         13. The subject has a current history of alcohol or substance abuse or has a history of
             alcohol or substance abuse that required treatment within the previous 12 months.

         14. The subject has a positive test result for human immunodeficiency virus (HIV) at
             screening.

         15. The subject has a history of poor compliance or unreliability.

         16. Females who are pregnant, nursing, or planning a pregnancy during their participation
             in the study.
      

Gender

All

Ages

6 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 



Administrative Informations


NCT ID

NCT04173650

Organization ID

EB IND


Responsible Party

Sponsor

Study Sponsor

Aegle Therapeutics


Study Sponsor

, , 


Verification Date

April 2022