Clinical trial NCT03529877: Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: RHEACELL GmbH & Co. KG
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
name: Granzer Regulatory Consulting & Services
name: Ticeba GmbH
First posted: 2018-05-18
Enrollment: 16
Sex: ALL
Minimum age (years): 0
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF])
measure: Assessment of adverse event (AE) occurrence
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score)
timeFrame: between baseline and week 12 post baseline (without LOCF)
measure: 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
timeFrame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (LOCF);
measure: Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB)
timeFrame: between baseline and week 12 post baseline (without LOCF)
measure: Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's EBDASI score)
timeFrame: between baseline and day 17 post baseline
measure: Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's iscorEB)
timeFrame: between baseline and day 17 post baseline
measure: Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's EBDASI score)
timeFrame: between baseline and day 35 post baseline
measure: Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's iscorEB)
timeFrame: between baseline and day 35 post baseline
measure: Inflammation (measured by panel of inflammation markers)
timeFrame: between baseline and day 17, day 35 and week 12 post baseline
measure: Pain assessment as per NRS
timeFrame: between baseline and day 17, day 35 and week 12 post baseline
measure: Itch assessment as per NRS
timeFrame: between baseline and day 17, day 35 and week 12 post baseline
measure: Differences in patient's quality of life in EB
timeFrame: between baseline and day 17, day 35 and week 12 post baseline
measure: Physical examination until Week 12;
timeFrame: At Screening, baseline, day 17, day 35 and week 12
measure: Vital signs: Body temperature until Week 12;
timeFrame: At Screening, baseline, day 17, day 35 and week 12
measure: Vital signs: Blood pressure until Week 12;
timeFrame: At Screening, baseline, day 17, day 35 and week 12
measure: Vital signs: Heart rate until Week 12;
timeFrame: At Screening, baseline, day 17, day 35 and week 12
measure: Overall survival at month 24
timeFrame: month 24 post baseline
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota, Masonic Cancer Center and Medical Center
state: Minnesota
city: Salzburg
country: Austria
facility: EB-Haus Austria; Salzburger Landeskliniken (SALK); Paracelsus Medizinische Privatuniversität Salzburg (PMU)
city: Paris
country: France
facility: Hôpital Saint-Louis; Département de dermatologie
city: Freiburg
country: Germany
facility: Department of Dermatology, Medical Center-University of Freiburg
city: London
country: United Kingdom
facility: King's College London; St John's Institute of Dermatology;
city: London
country: United Kingdom
facility: Great Ormond Street Hospital; Dermatology Department
Study officials:
affiliation: University of Minnesota, Masonic Cancer Center and Medical Center
name: Jakub Tolar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.