Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE April 24, 2018
First Posted Date  ICMJE May 18, 2018
Last Update Posted Date October 14, 2020
Actual Study Start Date  ICMJE January 16, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
  • 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
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2018)
  • Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's (EBDASI score) [ 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
  • Assessment of adverse event (AE) occurrenc [ Time Frame: Up to 12 months ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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
  • 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
  • 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
  • Overall survival at month 24 [ Time Frame: month 24 post baseline ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2018)
  • 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
  • Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB) [ Time Frame: Week 12 post baseline, 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Inflammation (measured by panel of inflammation markers) [ Time Frame: between baseline and day 17, day 35 and week 12 post baseline ]
  • 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.
  • 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.
  • 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
  • Physical examination [ 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.
  • Vital signs: Body temperature [ 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
  • Vital signs: Blood pressure [ 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
  • Vital signs: Heart rate [ 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
  • Overall survival at month 12 [ Time Frame: month 12 post baseline ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic ABCB5-positive Stem Cells for Treatment of Epidermolysis Bullosa
Official Title  ICMJE An Interventional, Multicenter, Single Arm, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-EB on Epidermolysis Bullosa (EB)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recessive Dystrophic Epidermolysis Bullosa
Intervention  ICMJE Biological: allo-APZ2-EB
intravenous infusion of allo-APZ2-EB
Other Name: allogeneic ABCB5-positive mesenchymal stem cells
Study Arms  ICMJE Experimental: allo-APZ2-EB
intravenous infusion, three doses of allo-APZ2-EB (2 x 10^6 cells/kg)
Intervention: Biological: allo-APZ2-EB
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 13, 2020)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2018)
18
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 55 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   France,   Germany,   United Kingdom,   United States
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT03529877
Other Study ID Numbers  ICMJE allo-APZ2-EB-II-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party RHEACELL GmbH & Co. KG
Study Sponsor  ICMJE RHEACELL GmbH & Co. KG
Collaborators  ICMJE
  • FGK Clinical Research GmbH
  • Granzer Regulatory Consulting & Services
  • Ticeba GmbH
Investigators  ICMJE
Principal Investigator: Jakub Tolar, MD, PhD University of Minnesota, Masonic Cancer Center and Medical Center
PRS Account RHEACELL GmbH & Co. KG
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP