A dual-center prospective phase I/II trial to establish safety, tolerability and to obtain first data on efficacy of losartan in children with recessive dystrophic epidermolysis bullosa (RDEB)

• Register: German Clinical Trials Register
• Last refreshed on: 8 April 2024
• Main ID: DRKS00009269
• Date of registration: 31/08/2016
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinikum Freiburg
• Public title: A dual-center prospective phase I/II trial to establish safety, tolerability and to obtain first data on efficacy of losartan in children with recessive dystrophic epidermolysis bullosa (RDEB)
• Scientific title: A dual-center prospective phase I/II trial to establish safety, tolerability and to obtain first data on efficacy of losartan in children with recessive dystrophic epidermolysis bullosa (RDEB) - REFLECT
• Date of first enrolment: 06/07/2017
• Target sample size: 30
• Recruitment status: Complete
• URL: http://drks.de/search/en/trial/DRKS00009269
• Study type: interventional
• Study design: Allocation: N/A: single arm study; Masking: Open (masking not used); Control: uncontrolled; Assignment: single; Study design purpose: treatment
• Phase: 1-2

Countries of recruitment

Austria, Germany

Contacts

• Name: Dimitra Kiritsi
• Affiliation: Universitätsklinikum Freiburg,Klink für Dermatologie und Venerologie

• Name: Dimitra Kiritsi
• Affiliation: Universitätsklinikum Freiburg,Klink für Dermatologie und Venerologie

Key inclusion & exclusion criteria

Inclusion criteria: 1.Written informed consent of parents or legal guardians 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 (starting from the 25th month of life);
4.Molecularly confirmed diagnosis of Umoderate to severe RDEBU. 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 guardians 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.

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 5PthP 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.Severe 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.Known or persistent abuse of medication, drugs or alcohol;
12.Persons who are in a relationship of dependence/employment with the sponsor or the investigator.
13.Current pregnancy or nursing period;
14.For female patients with menarche: unwillingness to use adequate contraception or to stay sexually abstinent during the course of the trial.


Age minimum: 25 Months
Age maximum: 16 Years
Gender: All

Health Condition(s) or Problem(s) studied

Q81.2

Epidermolysis bullosa dystrophica

Q81.2

Intervention(s)

Group 1: Losartan dose increase from 0.4 to 1.4 mg / kg every 16 weeks , a dose of 1.4 mg / kg in 24 weeks, and phasing out within 4 weeks

Primary Outcome(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, headaches and signs of peripheral shut down owing to the low blood pressure, leading to interruption of study medication;
2) immediate hypersensitivity reactions to the drug;
3) clinical relevant severe hypo- and hyperkalemia

Secondary Outcome(s)

(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.
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 system for the progression of Pseudosyndaktylien
• 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 )
• review of markers of fibrosis and inflammation in the skin and blood

Secondary ID(s)

2015-003670-32

Source(s) of Monetary Support

DEBRA International - DEBRA Austria

Ethics review

Status: Approved
Approval date: 09/08/2016
Contact:

[e-mail]

Ethik-Kommission der Albert-Ludwigs-Universität Freiburg

[phone]

[e-mail]

Results

• Date Completed: 12/02/2021
• URL: http://drks.de/search/en/trial/DRKS00009269#studyResults