REFLECT (symptom-RElieF with Losartan – EB Clinical Trial): A dual-center prospective phase II trial to establish safety, tolerability and efficacy of losartan in children with recessive dystrophic EB (Bruckner-Tuderman 5)Completed
|Project lead||Prof Leena Bruckner-Tuderman|
|Organisation||University of Freiburg Medical Center, Freiburg, GERMANY|
|Project budget||EUR 498,670.00 + time only extension 18 months|
|Start date / Duration||01. Mar 2016 / 68 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria, MSAP/EBEP Recommended|
|Research area||Symptom prevention & relief|
Short lay summary
Recessive dystrophic EB (RDEB), caused by collagen VII deficiency, is a chronic, disabling disorder with urgent need for efficacious treatments. In order to find relief and to ameliorate symptoms, we have designed a clinical trial with losartan to limit scarring in people with RDEB. Losartan is a drug that is given orally and has already been approved by the regulatory authorities for the treatment of another disease, namely high blood pressure. It has been used world-wide to treat thousands of people (adults and children) and been found safe. - An important and interesting point for people with RDEB is a second effect of losartan: it can prevent excessive scarring and fibrosis in mouse models.
In June 2017 we initiated the REFLECT-trial in Freiburg (A dual-center prospective phase II trial to establish safety, tolerability and efficacy of losartan in children with recessive dystrophic EB). The goal is to include 30 participants in the trial. In Freiburg we have already enrolled 25 patients. The patient visits were well-planned in advance and the trial runs well and without adverse effects or problems.
To ensure good communication and to discuss first results, we had two trial meetings in Freiburg with participants from the Dept. of Dermatology, the Dept. of Pediatric Cardiology and the Clinical Trial Unit (trial coordinator, monitors, trial assistant ect).
What did this project achieve?
The clinical trial has been successfully finished. All 29 patients, aged 2 to 14 years, were recruited in Freiburg. No safety concerns about the use of losartan in children with RDEB were raised. Losartan was tolerable and safe for the trial population. In addition, the final statistical analysis shows promising results regarding efficacy of the drug in RDEB. There was a significant improvement in the quality of life and itch scores. Markers of inflammation in the patients’ blood either remained stable or decreased. Patients’ weight increased significantly compared to data of untreated patients. Progression of the patients’ fusion of digits halted.
Based on the absence of concerns on safety and tolerability, the promising data on efficacy, and the data on the suitability of the scoring instruments for clinical trials in children with RDEB, the investigators at Freiburg already planned a Phase III trial. This international placebo-controlled trial will focus on the efficacy of losartan in ameliorating the RDEB manifestations and will be submitted for funding, after a commercial drug formulation is available.
Losartan has received orphan drug designation by the EMA and FDA for its use in RDEB and a patent has been granted for its use in fibrotic diseases, including EB.