Trial document




drksid header

  DRKS00009269

Trial Description

start of 1:1-Block title

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)

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

REFLECT

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

In this trial the safety, tolerability and first hints of a therapeutic effect of losartan in epodermolysis bullosa will be assessed. A further aim is that the symptoms of the recessive epidermolysis bullosa will be mitigated.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

REFLECT is a a dual-center prospective phase I/II trial to establish safety and tolerability of losartan in children with moderate to severe Epidermolysis bullosa.
The secondary objective is to 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 10 months.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00009269
  •   2016/08/31
  •   [---]*
  •   yes
  •   Approved
  •   157/16, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2015-003670-32 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Q81.2 -  Epidermolysis bullosa dystrophica
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   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
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

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

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

(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

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
  •   Austria
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2017/07/06
  •   30
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   25   Months
  •   16   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional 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.

end of 1:1-Block inclusion criteria add
start of 1:1-Block 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 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.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Freiburg
    • Breisacher Straße 153
    • 79110  Freiburg
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universitätsklinikum Freiburg,Klink für Dermatologie und Venerologie
    • Ms.  Dr.  Franziska  Schauer 
    • Hauptstrasse 7
    • 79104  Freiburg
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsklinikum Freiburg,Klink für Dermatologie und Venerologie
    • Ms.  Dr.  Franzika  Schauer 
    • Hauptstrasse 7
    • 79104  Freiburg
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • DEBRA International - DEBRA Austria
    • Am Heumarkt 27/1
    • 1030  Wien
    • Austria
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.