Recessive dystrophic epidermolysis bullosa (RDEB) MedDRA version: 20.0 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Losartan HEXAL
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: losartan potassium
Other descriptive name: LOSARTAN POTASSIUM
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent of parents or legal guardian obtained according to international guidelines and local laws; 2. Patient’s assent (if applicable according to patient’s age and understanding); 3. Male or female patients from 2 to 16 years (age of > 25 months); 4. Molecularly confirmed diagnosis of moderate to severe RDEB. If the patient is completely collagen VII-deficient, as shown by negative collagen VII immunofluorescence staining of a skin biopsy, no genetic confirmation of the diagnosis will be required for inclusion in the study. In case of residual collagen VII expression, the COL7A1 gene will be analyzed for mutations, to confirm the diagnosis of RDEB; 5. Ability of the patient (if applicable according to patient’s age and understanding), parents or legal guardian to understand the nature of the trial and trial-related procedures and to comply with them; 6. Able to travel to trial site for all clinic visits; Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Simultaneous or previous participation in any interventional trial within the past 3 months before entering this trial; participation in simultaneous registry and diagnostic trials during the trials is allowed; 2. Anemia with hemoglobin < 8 g/dl; 3. Hypotension (defined as age-related systolic blood pressure under the 5th percentile); 4. Cardiologic contraindications, such as severe heart failure with ejection fraction < 35%; 5. Patient requires any medications that are likely to cause interactions with losartan, e.g. rifampicin, ACE-inhibitors; 6. Renal artery stenosis or renal insufficiency with creatinine clearance < 30 ml/min; 7. Liver failure; 8. Severe, untreated electrolyte disturbances; 9. History of cancer or chronic viral infections (HBV, HCV, HIV); 10. Hypersensitivity to losartan or any of the excipients; 11. Current pregnancy or nursing period; 12. For female patients of child-bearing age: unwillingness to use adequate contraception or to stay sexually abstinent during the course of the trial; 13. Known or persistent abuse of medication, drugs or alcohol; 14. Persons who are in a relationship of dependence/employment with the sponsor or the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Establish tolerability and saftey of losartan in children with moderate to serve RDEB;Secondary Objective: Obtain first information on the efficacy of losartan in improving the disease manifestations and quality of life, and reducing inflammation and fibrosis in moderate to severe RDEB over a period of 9 months;Primary end point(s): Primary endpoint is defined as occurrence of a serious safety concern, specified as one of the following side effects of losartan: 1) clinically relevant severe hypotension i.e. the patient experiences continuous dizziness and headaches owing to the low blood pressure, leading to interruption of study medication; 2) immediate hypersensitivity reactions to the drug (Serious) adverse events, evaluated by monitoring heart rate and function and blood pressure, using echocardiography, home blood pressure monitoring devices, and blood tests throughout the study 3)clinical relevant severe hypo- und hyperkalemia ;Timepoint(s) of evaluation of this end point: the primary endpoint will be documented as SAE. All SAEs will be assessed from first intake of the IMP until 30 days after last intake of the IMP: day 1 until day 309 +/- 7 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy will be assessed using validated scoring systems for the clinical manifestations of RDEB : • Physician Global Assessment (PGA) • Birmingham Epidermolysis Bullosa Severity Score (BEBS) • Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) • Score of Colville and Terrill • Our own morphometric scoring instrument of pseudosyndactyly progression • Mayo Dysphagia Questionnaire-day 30 (MDQ-30) • Itch Assessment Scale for the Pediatric Burn Patients • Wong-Baker FACES Scale for Pain • Quality Of Life in EB (QOLEB) questionnaire • Children’s Dermatology Life Quality Index (CDLQI);Timepoint(s) of evaluation of this end point: PGA at visits 1 (day 1, visit 3 (day 57 +/-7days), visit 7 (day 281 +/- 7days) and EOS (end of study, day 399 +/- 7 days) | — |
Countries
Austria, Germany
Contacts
Public ContactCoordinating Investigator
Medical Center - University of Freiburg
Outcome results
None listed