Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa

NCT03529877 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: allo-APZ2-EB-II-01
• Study Type: interventional
• Target: 16
• Locations: 5 countries
• Sites: 6

Brief Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring overall improvement of EB symptoms) and safety (by monitoring adverse events) of three doses of allo-APZ2-EB administered intravenously to patients with recessive dystrophic epidermolysis bullosa (RDEB).

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Keywords

Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Somatic Cell Therapy; Mesenchymal Stem Cells; ABCB5; Allogeneic

Outcome Measures

Primary Outcomes (2)

• Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score), score), or last available post-baseline measurement if the Week 12 measurement is missing

  EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score

  Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF])

• Assessment of adverse event (AE) occurrence

  All AEs occurring during the clinical trial will be registered, documented and evaluated.

  Up to 24 months

Secondary Outcomes (16)

• Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score)

  between baseline and week 12 post baseline (without LOCF)

• Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB), or last available post-baseline measurement if the Week 12 measurement is missing

  Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (LOCF);

• Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB)

  between baseline and week 12 post baseline (without LOCF)

• Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's EBDASI score)

  between baseline and day 17 post baseline

• Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's iscorEB)

  between baseline and day 17 post baseline

Study Arms (1)

allo-APZ2-EB

EXPERIMENTAL

intravenous infusion, three doses of allo-APZ2-EB (2 x 10\^6 cells/kg)

Biological: allo-APZ2-EB

Interventions

allo-APZ2-EB BIOLOGICAL

intravenous infusion of allo-APZ2-EB

Also known as: allogeneic ABCB5-positive mesenchymal stem cells

allo-APZ2-EB

Eligibility Criteria

• Age: 0 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Male or female patients aged between 0 and ≤55 years;
• Staggered design for patient enrollment:
• at least 3 adult patients (safety assessment 2 weeks after last treatment of third patient),
• at least 3 patients ≥12 to \<18 years (safety assessment 2 weeks after first treatment of third patient),
• at least 3 patients ≥5 to \<12 years (safety assessment 2 weeks after first treatment of third patient), and
• at least 3 patients ≥12 months to \<5 years;
• patients 0 to \<12 months (only in the UK);
• \. Diagnosed with RDEB (combined diagnosis by genotype assessment \[mutation analysis\] and correlating phenotype assessment \[wound assessment\]), patients must have a negative immunofluorescence test result on salt-split skin against proteins of the basement membrane at Visit 1 (existing test results will be accepted);
• \. Patient is eligible to participate in this clinical trial based on general health condition at the investigator's discretion;
• US only:
• Patient is eligible to participate in this clinical trial based on general health condition assessed by specific lab values (Hematology: Absolute neutrophil count \>1000/mm3 and platelet count \>150,000/mcL; Coagulation: PT and PTT \<2x the upper limit of normal for age; Hepatic: AST and ALT \<2x the upper limit of normal for age; Renal: Creatinine \<2x the upper limit of normal for age; Pulmonary: Oxygen saturation \>92% on room air and without supplemental oxygen requirement);
• \. Patient/legal representative understands the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
• \. Women of childbearing potential must have a negative urine pregnancy test at Visit 1;
• \. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.

You may not qualify if:

• Tumor diseases or history of tumor disease;
• Known positive result for human immunodeficiency virus 1 and/or 2;
• Any known allergies to components of the IMP;
• Evidence of any other medical conditions (such as psychiatric illness or active infection) based on physical examination, or laboratory findings that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment; at investigators discretion;
• History of prior thrombosis or patients at risk for thrombosis;
• Clinically significant or unstable concurrent disease or other clinical contraindications (based upon investigator's judgment);
• Patient/legal representative anticipated to be unwilling or unable to comply with the requirements of the protocol;
• Pregnant or lactating women;
• Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
• Known abuse of alcohol, drugs, or medicinal products;
• Employees of the sponsor, or employees or relatives of the investigator.

Sponsors & Collaborators

• RHEACELL GmbH & Co. KG: lead
• FGK Clinical Research GmbH: collaborator
• Granzer Regulatory Consulting & Services: collaborator
• Ticeba GmbH: collaborator

Study Sites (6)

University of Minnesota, Masonic Cancer Center and Medical Center

Minneapolis, Minnesota, 55455, United States

Location

EB-Haus Austria; Salzburger Landeskliniken (SALK); Paracelsus Medizinische Privatuniversität Salzburg (PMU)

Salzburg, 5020, Austria

Location

Hôpital Saint-Louis; Département de dermatologie

Paris, 75010, France

Location

Department of Dermatology, Medical Center-University of Freiburg

Freiburg im Breisgau, 79104, Germany

Location

King's College London; St John's Institute of Dermatology;

London, SE1 9RT, United Kingdom

Location

Great Ormond Street Hospital; Dermatology Department

London, WC1N 3JH, United Kingdom

Location

Related Publications (3)

• Dieter K, Niebergall-Roth E, Daniele C, Fluhr S, Frank NY, Ganss C, Kiritsi D, McGrath JA, Tolar J, Frank MH, Kluth MA. ABCB5+ mesenchymal stromal cells facilitate complete and durable wound closure in recessive dystrophic epidermolysis bullosa. Cytotherapy. 2023 Jul;25(7):782-788. doi: 10.1016/j.jcyt.2023.01.015. Epub 2023 Mar 1.

  PMID: 36868990 DERIVED

• Kiritsi D, Dieter K, Niebergall-Roth E, Fluhr S, Daniele C, Esterlechner J, Sadeghi S, Ballikaya S, Erdinger L, Schauer F, Gewert S, Laimer M, Bauer JW, Hovnanian A, Zambruno G, El Hachem M, Bourrat E, Papanikolaou M, Petrof G, Kitzmuller S, Ebens CL, Frank MH, Frank NY, Ganss C, Martinez AE, McGrath JA, Tolar J, Kluth MA. Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. JCI Insight. 2021 Nov 22;6(22):e151922. doi: 10.1172/jci.insight.151922.

  PMID: 34665781 DERIVED

• Kerstan A, Niebergall-Roth E, Esterlechner J, Schroder HM, Gasser M, Waaga-Gasser AM, Goebeler M, Rak K, Schrufer P, Endres S, Hagenbusch P, Kraft K, Dieter K, Ballikaya S, Stemler N, Sadeghi S, Tappenbeck N, Murphy GF, Orgill DP, Frank NY, Ganss C, Scharffetter-Kochanek K, Frank MH, Kluth MA. Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data. Cytotherapy. 2021 Feb;23(2):165-175. doi: 10.1016/j.jcyt.2020.08.012. Epub 2020 Oct 1.

  PMID: 33011075 DERIVED

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica; Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Study Officials

• Jakub Tolar, MD, PhD

  University of Minnesota, Masonic Cancer Center and Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 18, 2018
• Study Start: February 16, 2019
• Primary Completion: November 26, 2021
• Study Completion: November 26, 2021
• Last Updated: October 7, 2022

Record last verified: 2022-03

Locations

GB (2); US (1); FR (1); AU (1); DE (1)