Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa

Recessive Dystrophic Epidermolysis Bullosa Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03529877
• Other study ID #: allo-APZ2-EB-II-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 16, 2019
• Est. completion date: November 26, 2021

Study information

• Verified date: March 2022
• Source: RHEACELL GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This is an interventional, single arm, non-randomized, open label, phase I/IIa clinical trial to investigate the efficacy and safety of the IMP allo-APZ2-EB in patients with RDEB.

Patients will undergo treatment with the IMP (three repeated intravenous applications) and will be followed up for efficacy for 12 weeks. To assess long-term safety of allo-APZ2-EB one follow-up visit at Month 12 and one follow-up visit at Month 24 post IMP applications is included.

Determination of the EB linked symptoms and quality of life will be assessed by using the EBDASI score, the iscorEB, the change in pain and itch perception, and patient's quality of life in EB. The wound healing process will be documented by photography.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 26, 2021
• Est. primary completion date: November 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Male or female patients aged between 0 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;

5. patients 0 to <12 months (only in the UK);

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;

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);

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.

Exclusion Criteria:

1. Tumor diseases or history of tumor disease;

2. Known positive result for human immunodeficiency virus 1 and/or 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.

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa Dystrophica
• Recessive Dystrophic Epidermolysis Bullosa

Intervention

Biological:
• allo-APZ2-EB
intravenous infusion of allo-APZ2-EB

Locations

Country	Name	City	State
Austria	EB-Haus Austria; Salzburger Landeskliniken (SALK); Paracelsus Medizinische Privatuniversität Salzburg (PMU)	Salzburg
France	Hôpital Saint-Louis; Département de dermatologie	Paris
Germany	Department of Dermatology, Medical Center-University of Freiburg	Freiburg
United Kingdom	Great Ormond Street Hospital; Dermatology Department	London
United Kingdom	King's College London; St John's Institute of Dermatology;	London
United States	University of Minnesota, Masonic Cancer Center and Medical Center	Minneapolis	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
RHEACELL GmbH & Co. KG	FGK Clinical Research GmbH, Granzer Regulatory Consulting & Services, Ticeba GmbH

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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])
Primary	Assessment of adverse event (AE) occurrence	All AEs occurring during the clinical trial will be registered, documented and evaluated.	Up to 24 months
Secondary	Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score)	EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score	between baseline and week 12 post baseline (without LOCF)
Secondary	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	iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score	Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (LOCF);
Secondary	Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB)	iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score	between baseline and week 12 post baseline (without LOCF)
Secondary	Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's EBDASI score)	EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score	between baseline and day 17 post baseline
Secondary	Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's iscorEB)	iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score	between baseline and day 17 post baseline
Secondary	Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's EBDASI score)	EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score	between baseline and day 35 post baseline
Secondary	Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's iscorEB)	iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score	between baseline and day 35 post baseline
Secondary	Inflammation (measured by panel of inflammation markers)	A panel of inflammation markers will be measured and evaluated.	between baseline and day 17, day 35 and week 12 post baseline
Secondary	Pain assessment as per NRS	Pain assessment as per numerical rating scale (NRS) will be evaluated.	between baseline and day 17, day 35 and week 12 post baseline
Secondary	Itch assessment as per NRS	Itch assessment as per numerical rating scale (NRS) will be evaluated.	between baseline and day 17, day 35 and week 12 post baseline
Secondary	Differences in patient's quality of life in EB	Assessment of quality of life data using an EB-specific quality of life questionnaire	between baseline and day 17, day 35 and week 12 post baseline
Secondary	Physical examination until Week 12;	A full physical examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.	At Screening, baseline, day 17, day 35 and week 12
Secondary	Vital signs: Body temperature until Week 12;	Body temperature will be evaluated at Screening, baseline, day 17, day 35 and week 12	At Screening, baseline, day 17, day 35 and week 12
Secondary	Vital signs: Blood pressure until Week 12;	Blood pressure will be evaluated at Screening, baseline, day 17, day 35 and week 12	At Screening, baseline, day 17, day 35 and week 12
Secondary	Vital signs: Heart rate until Week 12;	Heart rate will be evaluated at Screening, baseline, day 17, day 35 and week 12	At Screening, baseline, day 17, day 35 and week 12
Secondary	Overall survival at month 24		month 24 post baseline