Recessive Dystrophic Epidermolysis Bullosa
Conditions
Keywords
Epidermolysis Bullosa, Epidermolysis Bullosa Dystrophica, Skin Abnormalities, Congenital Abnormalities, Skin Diseases, Genetic, Somatic Cell Therapy, Mesenchymal Stem Cells, ABCB5, Allogeneic
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.
Interventions
BIOLOGICALallo-APZ2-EB
intravenous infusion of allo-APZ2-EB
Sponsors
FGK Clinical Research GmbH
Granzer Regulatory Consulting & Services
Ticeba GmbH
RHEACELL GmbH & Co. KG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | Up to 24 months | All AEs occurring during the clinical trial will be registered, documented and evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall improvement of EB symptoms after 12 weeks (measured by percentage change of patient's iscorEB) | 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) | 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) | 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) | 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) | 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) | 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 | between baseline and day 17, day 35 and week 12 post baseline | Pain assessment as per numerical rating scale (NRS) will be evaluated. |
| Overall improvement of EB symptoms after 12 weeks (measured by percentage change of a patient's EBDASI score) | between baseline and week 12 post baseline (without LOCF) | EBDASI: epidermolysis bullosa disease activity and scarring index; measured in percentage change to baseline score |
| Differences in patient's quality of life in EB | 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; | 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; | 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; | 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; | 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 | month 24 post baseline | — |
| Itch assessment as per NRS | between baseline and day 17, day 35 and week 12 post baseline | Itch assessment as per numerical rating scale (NRS) will be evaluated. |
| 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 | 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 |
Countries
Austria, France, Germany, United Kingdom, United States
Outcome results
None listed