MSC EVs in Dystrophic Epidermolysis Bullosa

Studies

Study First Submitted Date 2019-11-18
Study First Posted Date 2019-11-22
Last Update Posted Date 2023-05-23
Start Month Year October 2023
Primary Completion Month Year July 2024
Verification Month Year May 2023
Verification Date 2023-05-31
Last Update Posted Date 2023-05-23

Detailed Descriptions

Sequence: 20779579
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.

Conditions

Sequence: 52319388
Name Dystrophic Epidermolysis Bullosa
Downcase Name dystrophic epidermolysis bullosa

Id Information

Sequence: 40264598
Id Source org_study_id
Id Value EB IND

Design Groups

Sequence: 55758178
Group Type Experimental
Title AGLE 102
Description Treatment arm

Interventions

Sequence: 52630407
Intervention Type Drug
Name AGLE 102
Description Exosomes from MSCs

Keywords

Sequence: 80073415
Name Exosomes
Downcase Name exosomes

Design Outcomes

Sequence: 177926588 Sequence: 177926589
Outcome Type primary Outcome Type secondary
Measure Dose Limiting Toxicity Measure Wound size evaluation
Time Frame 8 months Time Frame 8 months
Description This study examines a dose escalation, Dose Limiting Toxicity (as defined in the NCI/CTCAE v4.0 grading scale) Description 1. Wound Size Evaluation

Target wounds will be measured using Silhouette® (Aranz Medical
Direct wound tracings will also be performed.

Browse Conditions

Sequence: 194050773 Sequence: 194050774 Sequence: 194050775 Sequence: 194050776 Sequence: 194050777 Sequence: 194050778 Sequence: 194050779 Sequence: 194050780 Sequence: 194050781 Sequence: 194050782
Mesh Term Epidermolysis Bullosa Mesh Term Epidermolysis Bullosa Dystrophica Mesh Term Skin Abnormalities Mesh Term Congenital Abnormalities Mesh Term Skin Diseases, Genetic Mesh Term Genetic Diseases, Inborn Mesh Term Skin Diseases Mesh Term Skin Diseases, Vesiculobullous Mesh Term Collagen Diseases Mesh Term Connective Tissue Diseases
Downcase Mesh Term epidermolysis bullosa Downcase Mesh Term epidermolysis bullosa dystrophica Downcase Mesh Term skin abnormalities Downcase Mesh Term congenital abnormalities Downcase Mesh Term skin diseases, genetic Downcase Mesh Term genetic diseases, inborn Downcase Mesh Term skin diseases Downcase Mesh Term skin diseases, vesiculobullous Downcase Mesh Term collagen diseases Downcase Mesh Term connective tissue diseases
Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48458092
Agency Class INDUSTRY
Lead Or Collaborator lead
Name Aegle Therapeutics

Design Group Interventions

Sequence: 68348855
Design Group Id 55758178
Intervention Id 52630407

Eligibilities

Sequence: 30851195
Gender All
Minimum Age 6 Years
Maximum Age N/A
Healthy Volunteers No
Criteria Inclusion Criteria:

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.
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.
Subjects who have one or more active wounds (unroofed EB erosions) each between 10 and 50 cm2 on arms, legs, or trunk.
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.
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.
Subjects must be willing to comply with the protocol requirements.
Subjects must be accessible for wound treatments and assessment visits.
Subjects must have a negative urine test for drugs of abuse at the screening visit.
Female subjects willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period.
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:
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
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:

The subject has clinical evidence of systemic infection.
The subject has a history or bone marrow transplantation.
The subject has evidence of autoimmune disease, including insulin-dependent diabetes.
The subject has wounds that are considered by the investigator as likely to heal within 1 month after standard therapy.
The subject has clinical evidence of an active infection at the wound site.
The subject has evidence of significant wound healing before treatment (i.e., ≥ 20% closure of wound during the first month observation period treatment).
The subject has a wound that extends across the fingers, toes, pubic or perineum region.
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.
The subject has a history of coagulopathy.
The subject currently uses systemic steroids or immunosuppressive agents.
The subject is allergic to human albumin, streptomycin, or penicillin.
The subject is a potential recipient of tissue or organ transplantation.
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.
The subject has a positive test result for human immunodeficiency virus (HIV) at screening.
The subject has a history of poor compliance or unreliability.
Females who are pregnant, nursing, or planning a pregnancy during their participation in the study.

Adult True
Child True
Older Adult True

Calculated Values

Sequence: 254267621
Registered In Calendar Year 2019
Were Results Reported False
Has Single Facility False
Minimum Age Num 6
Minimum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 1

Designs

Sequence: 30597053
Allocation N/A
Intervention Model Single Group Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking None (Open Label)
Intervention Model Description This is a phase 1/2A, non-randomized, multicenter, ascending dose, study to assess the effectiveness and safety of AGLE-102 on lesions in subjects with EB.

Responsible Parties

Sequence: 28963534
Responsible Party Type Sponsor