Study to investigate the efficacy and safety of allo-APZ2-EB on wound healing of epidermolysis bullosa (EB)

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2018-001009-98-GB
• Date of registration: 25/10/2018
• Prospective Registration: No
• Primary sponsor: RHEACELL GmbH & Co. KG
• Public title: Study to investigate the efficacy and safety of allo-APZ2-EB on wound healing of epidermolysis bullosa (EB)
• Scientific title: An interventional, multicenter, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of allo-APZ2-EB on epidermolysis bullosa (EB)
• Date of first enrolment: 18/09/2018
• Target sample size: 16
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001009-98
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Italy, United Kingdom, United States

Contacts

• Name: Information Office
• Affiliation: RHEACELL GmbH & Co. KG

• Name: Information Office
• Affiliation: RHEACELL GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients aged between 0 months and =55 years, Staggered design for patient enrollment:
1.) at least 3 adult patients (safety assessment 2 weeks after last treatment of third patient),
2.) at least 3 patients =12 to <18 years (safety assessment 2 weeks after first treatment of third patient),
3.) at least 3 patients =5 to <12 years (safety assessment 2 weeks after first treatment of third patient), and
4.) at least 3 patients =12 months to <5 years (safety assessment 2 weeks after first treatment of third patient), and
5.) patients 0 to <12 months;
2. 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);
3. Patient is eligible to participate in this clinical trial based on general health condition at the investigator’s discretion;
4. Patient/legal representative understands the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
5. Women of childbearing potential must have a negative urine pregnancy test at Visit 1;
6. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Tumor diseases or history of tumor disease;
2. Tested positive for human immunodeficiency virus 1 and/or 2 (HIV-1, HIV-2);
3. Any known allergies to components of the IMP;
4. 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;
5. History of prior thrombosis or patients at risk for thrombosis;
6. Clinically significant or unstable concurrent disease or other clinical contraindications (based upon investigator’s judgment);
7. Patient/legal representative anticipated to be unwilling or unable to comply with the requirements of the protocol;
8. Pregnant or lactating women;
9. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
10. Previous participation in this clinical trial (except for screening failures due to an exclusion criterion);
11. Known abuse of alcohol, drugs, or medicinal products;
12. Employees of the sponsor, or employees or relatives of the investigator.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recessive dystrophic epidermolysis bullosa (RDEB)
MedDRA version: 20.0 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: allo-APZ2-EB
Product Code: allo-APZ2-EB
Pharmaceutical Form: Suspension for injection
Current Sponsor code: T202-3
Other descriptive name: Allogeneic skin-derived ABCB5-positive mesenchymal stem cells
Concentration unit: million organisms/ml million organisms/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): 1. Efficacy endpoint:
Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient’s EBDASI score), or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF]).
2. Safety endpoint:
Adverse events.

Secondary Objective: Not applicable.

Timepoint(s) of evaluation of this end point: 1. Week 12, after first IMP application or timepoint of last observation carried forward.
2. At day -7, 0, 17, 35, week 12, month 12, 24 .

Main Objective: The aim of this clinical trial is to investigate the efficacy (by monitoring overall improvement of EB symptoms measured by epidermolysis bullosa disease activity and scarring index [EBDASI] score and instrument for scoring clinical outcome of research for epidermolysis bullosa [iscorEB], wound healing assessed by photo documentation, and patients quality of life in EB [QOLEB] assessment) and safety (by monitoring adverse events [AEs]) of the IMP allo APZ2 EB administered intravenously to patients with EB in three applications (Day 0, Day 17 ±3, Day 35 ±3).

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints:
1. Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient’s EBDASI score, without LOCF);
2. 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 (LOCF);
3. Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient’s iscorEB, without LOCF);
4. Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient’s EBDASI score and patient’s iscorEB);
5. Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient’s EBDASI score and patient’s iscorEB);
6. Inflammation (measured by panel of inflammation markers);
7. Pain assessment as per numerical rating scale (NRS);
8. Itch assessment as per NRS;
9. Assessment of QOLEB.

Secondary safety endpoint:
10. Physical examination and vital signs until Week 12;
11. Overall survival at Month 12 and 24.

Timepoint(s) of evaluation of this end point: 1. Week 12, after first IMP application;
2. Week 12, after first IMP application or timepoint of last observation carried forward;
3. Week 12, after first IMP application;
4. Day 17, after first IMP application;
5. Day 35, after first IMP application;
6. Day 0, 17 and 35 and week 12 after first IMP application;
7. Day 17 and 35 and week 12, after first IMP application;
8. Day 17 and 35 and week 12, after first IMP application;
9. Day 17 and 35 and week 12, after first IMP application;
10. Day 17, 35 and week 12 after first IMP application;
11. Month 12 and 24 after first IMP application;

Secondary ID(s)

allo-APZ2-EB-II-01

2018-001009-98-DE

Source(s) of Monetary Support

RHEACELL GmbH & Co. KG

Ethics review

Status: Approved
Approval date: 18/09/2018
Contact: