BIOOPA dressing will be used in the treatment of wounds in the course of Epidermolysis Bullosa, chronic venous leg ulceration and thermal injury (second degree burn). MedDRA version: 20.0 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BIOOPA dressing
Pharmaceutical Form: Transdermal system
INN or Proposed INN: Human Allogeneic WJ-MSCs
Current Sponsor code: Human Allogeneic WJ-MSCs
Other descriptive name: WHARTON’S JEL
Sponsors
Medical University of Warsaw
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for Epidermolysis Bullosa Cohort: 1)Signed written informed consent prior to beginning study- related procedures. 2)Male or female: a)Children, aged 5 - 18 years at date of inclusion into the study b)Adults, aged 18 – 60 years at date of inclusion into the study 3)Established clinical diagnosis of recessive, severe, generalized type of EB (dystrophic and joint types) 4)Skin wound, which: a)is located on the trunk or extremities, b)is not healing for period of minimum 3 weeks c)with a surface area between 3 – 30 cm2 (children), 10 – 30 cm2 (adults) Inclusion criteria number 4) for Patients with at least two open skin wounds of similar size: 4)two open skin wounds of similar size (surface area difference +/– 15%), which: a)are located on the trunk and/or extremities, b)are not healing for period of minimum 3 weeks c)each with a surface area between 3 – 30 cm2 (children), 10 – 30 cm2 (adults) Inclusion Criteria for Venous Leg Ulcers Cohort: 1)Signed written informed consent prior to beginning study- related procedures. 2)Male or female, aged 40 – 80 years at date of inclusion into the study 3)Presence of a venous leg ulcer (VLU) between the knee and ankle: a)with a surface area between: 25 cm2 - 100 cm2 b)that has been present for at least 3 month 4)Adequate circulation to the affected lower extremity, defined as an Ankle Brachial Index (ABI) greater than 0.75. 5)Venous insufficiency confirmed by duplex Doppler ultrasound. 6)Have a Clinical severity, Etiology or cause, Anatomy and Pathophysiology ulcer classification (CEAP) Grade C6: an open venous ulcer. Inclusion Criteria for Thermal Injury Cohort: 1)Signed written informed consent prior to beginning study- related procedures. 2)Male or female adults, aged 18 – 60 years at date of inclusion into the study 3)Patient with second-degree burn (II) or third-degree burn (III) wound (s) caused by thermal injury 4)Target burn wound surface area: 5 – 50 cm2 5)The area of total burn injury below 10% TBSA. Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Epidermolysis Bullosa Cohort: 1)Diseases or conditions that could interfere with the assessment of safety and efficacy of the study treatment and compliance of the subject with study visits/procedures. 2)Chronic or current active infection or disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis B, active Hepatitis C, and known Human Immunodeficiency Virus (HIV) disease. All HIV-positive subjects are excluded from this trial 3)EB target wound with clinical signs (e.g. wound exudate) of local infection at day of baseline visit. 4)Administration of immunosuppressive agents. Use of systemic steroids within 30 days before baseline visit should be discussed with Lead Principal Investigator to determine patient’s eligibility. 5)Current and/or former malignancy including basal cell carcinomas and squamous cell carcinomas. 6)Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry. 7)Pregnant or nursing women. Exclusion criteria for Venous Leg Ulceration Cohort: 1)Diseases or conditions that could interfere with the assessment of safety and efficacy of the study treatment and compliance of the subject with study visits/procedures. 2)Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis B, active Hepatitis C, and known Human Immunodeficiency Virus (HIV) disease. All HIV-positive subjects are excluded from this trial. 3)Documented history of osteomyelitis at the target wound location within 6 months preceding the Baseline Visit. 4)Clinical evidence (e.g. wound exudate) of target ulcer infection at the day of baseline visit. 5)Administration of immunosuppressive agents. Use of systemic steroids within 30 days before baseline visit should be discussed with Principal Investigator to determine patient’s eligibility. 6)Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit. 7)Taking, or have participated in other clinical studies involving stem cell therapy. 8)Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry. 9)Ulcer, which in the opinion of the Investigator is suspicious for cancer. 10)Current and/or former malignancy. 11)Poorly controlled type 2 diabetes mellitus defined as with glycosylated haemoglobin (HbA1c >7,0%) 12)Pregnant or nursing women. Exclusion Criteria for Burn Cohort 1)Diseases or conditions that could interfere with the assessment of safety and efficacy of the study treatment and compliance of the subject with study visits/procedures. 2)Airway burns. 3)Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis B, active Hepatitis C, and known Human Immunodeficiency Virus (HIV) disease. All HIV-positive subjects are excluded from this trial. 4)Administration of immunosuppressive agents. Use of systemic steroids within 30 days before baseline visit should be discussed with Principal Investigator to de
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to evaluate the safety of BIOOPA dressing. ;Secondary Objective: To evaluate the efficacy of BIOOPA dressing. To evaluate the efficacy of BIOOPA dressing in the treatment of chronic wounds. To evaluate Immunogenicity/ immunization To evaluate cells proliferation and vascularization To compare efficacy of BIOOPA dressing to standard treatment in the treatment of chronic wounds in the course of EB for patients with two wounds of similar area To evaluate changes in pain To evaluate changes in itch To evaluate presence of collagen VII for patients with Dystrophic Epidermolysis Bullosa. To evaluate presence of collagen VII, Integrin and Laminin for patients with Junctional Epidermolysis Bullosa. To evaluate Differences in quality of life data.;Primary end point(s): Evaluation of BIOOPA dressing safety by: Incidence and severity of adverse events related to the ATIMP. Incidence and severity of serious adverse events related to the ATIMP Incidences of Grade 3 and 4 wound (with BIOOPA dressing) infections. Incidence of BIOOPA rejection. ;Timepoint(s) of evaluation of this end point: Evaluation of BIOOPA dressing safety will be evaluated at every patient's visit, starting from visit 2 (baseline visit) to visit 8 (follow-up visit). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: BIOOPA dressing engraftment - assessed by wound biopsy at Day 30. Evaluation of efficacy of BIOOPA dressing - will performed at each patient's visit starting from visit 2 to visit 8. Evaluation of immunogenicity/immunization will be assessed at visit 7. Evaluation of cells proliferation and vascularization will be performed at visit 5 by wound biopsy. Change in pain will be assessed at each patient's visit. Change in itch will be assessed at each patient's visit. Level of collagen VII for patient with dystrophic type of EB will be assesed by wound biopsy at visit 5. Level of collagen VII, Integrin and Laminin for patients with junctional EB will be measured by wound biopsy at visit 5. Quality of life will be assessed at visit 2, visit 5 and at visit 7.;Secondary end point(s): BIOOPA dressing engraftment The mean change in treated wound area (cm2) Percentage change in wound surface area reduction Complete response defined as complete (100%) wound healing Partial response defined as reduce the wound surface area (cm2) by 50% Time to complete response defined as time, in days, from baseline to initial observation of complete wound healing. Time to partial response, defined as time, in days, from baseline to initial observation of 50% reduction of wound surface area. Evaluation of Immunogenicity/ immunization by assessment of blood serum markers: % PRA, CD4 and CD8 level, TNF-a, IL-6. Evaluation of cells proliferation and vascularization by wound biopsy and assessment of: Mesenchymal Cells markers (CD105, CD90, CD73), Kai 67, IL-2R (CD25), Vimentyn, P16, p53 and mutant p53 , KRT5, KRT14, Integrin beta-1 (CD29) The mean change in treated wound surface area (cm2) from baseline in wounds treated with BIOOPA dressing compared with those treated with standard, dressing for patients with two similar wounds. Changes in itch using the numeric rating scale. Changes in pain using the numeric rating scale. Level of collagen VII i | — |
Countries
Poland
Contacts
Public ContactCezary Kowalewski
Medical University of Warsaw
Outcome results
None listed