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Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03529877
Recruitment Status : Active, not recruiting
First Posted : May 18, 2018
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
FGK Clinical Research GmbH
Granzer Regulatory Consulting & Services
Ticeba GmbH
Information provided by (Responsible Party):
RHEACELL GmbH & Co. KG

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).

Condition or disease Intervention/treatment Phase
Recessive Dystrophic Epidermolysis Bullosa Biological: allo-APZ2-EB Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 16, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: allo-APZ2-EB
intravenous infusion, three doses of allo-APZ2-EB (2 x 10^6 cells/kg)
Biological: allo-APZ2-EB
intravenous infusion of allo-APZ2-EB
Other Name: allogeneic ABCB5-positive mesenchymal stem cells




Primary Outcome Measures :
  1. 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 [ Time Frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward [LOCF]) ]
    EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score

  2. Assessment of adverse event (AE) occurrence [ Time Frame: Up to 24 months ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.


Secondary Outcome Measures :
  1. Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score) [ Time Frame: between baseline and week 12 post baseline (without LOCF) ]
    EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score

  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 [ Time Frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing (LOCF); ]
    iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score

  3. Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB) [ Time Frame: between baseline and week 12 post baseline (without LOCF) ]
    iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score

  4. Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's EBDASI score) [ Time Frame: between baseline and day 17 post baseline ]
    EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score

  5. Overall improvement of EB symptoms at Day 17 (measured by percentage change of a patient's iscorEB) [ Time Frame: between baseline and day 17 post baseline ]
    iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score

  6. Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's EBDASI score) [ Time Frame: between baseline and day 35 post baseline ]
    EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score

  7. Overall improvement of EB symptoms at Day 35 (measured by percentage change of a patient's iscorEB) [ Time Frame: between baseline and day 35 post baseline ]
    iscorEB: instrument for scoring clinical outcome of research for epidermolysis bullosa; measured in percentage change to baseline score

  8. Inflammation (measured by panel of inflammation markers) [ Time Frame: between baseline and day 17, day 35 and week 12 post baseline ]
    A panel of inflammation markers will be measured and evaluated.

  9. Pain assessment as per NRS [ Time Frame: between baseline and day 17, day 35 and week 12 post baseline ]
    Pain assessment as per numerical rating scale (NRS) will be evaluated.

  10. Itch assessment as per NRS [ Time Frame: between baseline and day 17, day 35 and week 12 post baseline ]
    Itch assessment as per numerical rating scale (NRS) will be evaluated.

  11. Differences in patient's quality of life in EB [ Time Frame: between baseline and day 17, day 35 and week 12 post baseline ]
    Assessment of quality of life data using an EB-specific quality of life questionnaire

  12. Physical examination until Week 12; [ Time Frame: At Screening, baseline, day 17, day 35 and week 12 ]
    A full physical examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.

  13. Vital signs: Body temperature until Week 12; [ Time Frame: At Screening, baseline, day 17, day 35 and week 12 ]
    Body temperature will be evaluated at Screening, baseline, day 17, day 35 and week 12

  14. Vital signs: Blood pressure until Week 12; [ Time Frame: At Screening, baseline, day 17, day 35 and week 12 ]
    Blood pressure will be evaluated at Screening, baseline, day 17, day 35 and week 12

  15. Vital signs: Heart rate until Week 12; [ Time Frame: At Screening, baseline, day 17, day 35 and week 12 ]
    Heart rate will be evaluated at Screening, baseline, day 17, day 35 and week 12

  16. Overall survival at month 24 [ Time Frame: month 24 post baseline ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03529877


Locations
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United States, Minnesota
University of Minnesota, Masonic Cancer Center and Medical Center
Minneapolis, Minnesota, United States, 55455
Austria
EB-Haus Austria; Salzburger Landeskliniken (SALK); Paracelsus Medizinische Privatuniversität Salzburg (PMU)
Salzburg, Austria, 5020
France
Hôpital Saint-Louis; Département de dermatologie
Paris, France, 75010
Germany
Department of Dermatology, Medical Center-University of Freiburg
Freiburg, Germany, 79104
United Kingdom
King's College London; St John's Institute of Dermatology;
London, United Kingdom, SE1 9RT
Great Ormond Street Hospital; Dermatology Department
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
RHEACELL GmbH & Co. KG
FGK Clinical Research GmbH
Granzer Regulatory Consulting & Services
Ticeba GmbH
Investigators
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Principal Investigator: Jakub Tolar, MD, PhD University of Minnesota, Masonic Cancer Center and Medical Center
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Responsible Party: RHEACELL GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT03529877    
Other Study ID Numbers: allo-APZ2-EB-II-01
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RHEACELL GmbH & Co. KG:
Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Somatic Cell Therapy
Mesenchymal Stem Cells
ABCB5
Allogeneic
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases