SNT-IV-005 LEROS study
Research type
Research Study
Full title
External natural history controlled, open-label intervention study to assess the efficacy and safety of long-term treatment with Raxone® in Leber’s hereditary optic neuropathy (LHON)
IRAS ID
200900
Contact name
Patrick Yu Wai Man
Contact email
Sponsor organisation
Santhera Pharmaceuticals (Switzerland) Limited
Eudract number
2015-004405-16
Duration of Study in the UK
3 years, 10 months, 16 days
Research summary
Summary of Research
This is a Phase 4 clinical research study, called LEROS.
The LEROS study is aiming to find out more about the effectiveness and safety of the study drug (Raxone) in the long-term treatment of Leber’s hereditary optic neuropathy (LHON). The study drug has already been approved in the European Union for the treatment of LHON.
Approximately 250 patients at 25 study centres across several European countries will take part in this study.Summary of Results
The LEROS study: External natural history controlled, open-label intervention study to assess the efficacy and safety of long-term treatment with Raxone® in Leber’s Hereditary Optic Neuropathy (LHON)LEROS patients
A total of 199 patients with LHON took part in the LEROS study. These patients came from 10 countries around the world. All of the patients took Raxone® tablets at a dose of 900 mg each day (2 tablets 3 times daily with meals) for 24 months.
What kinds of tests did the patients undertake?
In order to measure the effects of Raxone® treatment on eyesight, each patient had to take a vision test using eye charts. The eye charts used for measuring eyesight in LEROS are called ETDRS charts. These charts have different sized letters on each line, from big to small. The smaller the letters you can read, the better your eyesight.
The patients' eyesight was measured regularly throughout the study using these charts.
In addition to the eyesight tests, the patients also underwent safety tests. These were physical exams, eye exams, and measurements of basic bodily functions like temperature and pulse rate. Blood and urine samples were also taken, to measure the concentrations of certain chemicals (like electrolytes, glucose, proteins, etc). This gives information on whether the body is functioning normally when the patient is taking Raxone®.
What were the main questions addressed in the LEROS study?
The main question asked in the LEROS study was whether Raxone® treatment could either improve, or prevent the worsening ("stabilize") the eyesight of patients who receive treatment within 1 year after their symptoms began. Together, this improvement or stabilization in eyesight is called "clinically-relevant benefit".
The results of the LEROS study were compared against those of untreated LHON patients. The data from untreated LHON patients were taken from medical records that were provided by study centers around the world. These are called the "Natural History" controls, because they give a picture of what happens if the disease is not treated.
What were the results of the LEROS study?
Raxone® treatment showed a beneficial effect on patients' eyesight. After taking Raxone® for 12 months, 42 .3% of patients experienced a clinically-relevant benefit (compared to 20.7% of the Natural History controls). These patients experienced either an improved or stabilized vision.
When looking at the eyes of the patients, 33 .1% of eyes recovered some of their lost vision (compared to 18.1% of Natural History controls). This means they were able to read more letters on the ETDRS charts. Also, 64 .5% of eyes maintained their vision (compared to 22.5% of Natural History controls). This means that their vision did not get worse, but they could still read the same number of letters on the ETDRS charts as they could in the beginning of the study.
The LEROS study also divided the patients into 3 groups, based on eyesight:
1. Group 1- those who were not legally blind and who could read some letters on the ETDRS charts,
2. Group 2 - those who were legally blind but who could still read a few letters on the ETDRS charts, and
3. Group 3 - those who could no longer read any letters on the ETDRS charts ("off-chart").
At the end of the study (after 24 months' Raxone® treatment), there were more patients in Group 1 (the group of patients with the best vision). This number improved from 23.3% at 6 months, to 42.9% at the end of the study. In Group 2, there were 50% at 6 months and 41.4% at the end of the study. There were fewer patients in Group 3 (the group with the worst eyesight) at the end of the study: 26.7% at 6 months, compared to 15.7% at the end of the study.
These results show that Raxone® treatment can help to prevent worsening of eyesight due to LHON. In some patients, Raxone® treatment can help to recover some lost eyesight.
What about patients who received treatment later than 1 year after their symptoms began?
These patients also experienced a benefit with Raxone® treatment. When looking at the eyes of this group of patients, 50 .3% of eyes had a clinically-relevant benefit (compared to 38.6% of Natural History controls). Their vision either improved or stabilized.
Over the course of the study, some patients in Group 3 (the group with the worst eyesight) experienced an improvement in their vision, from 26.5% at 6 months to 40.9% at the end of the study.
At the end of the study, there were fewer patients in Group 3 (the group with the worst eyesight): there were 23.5% in this group at 6 months, compared to 16.4% at the end of the study.
These results show that Raxone® treatment can also help improve or prevent worsening of eyesight in patients who receive treatment later than 1 year after their symptoms began.
Why was there some improvement in untreated patients?
Sometimes, a few untreated patients show spontaneous vision recovery or stabilization. But this number was always much smaller than in patients treated with Raxone®.
How safe is Raxone®?
Most of the side effects reported in the LEROS study were mild or moderate. Thirteen patients who received Raxone® treatment reported severe side effects. One patient died of liver failure. The patient's doctor assessed this death as not related to Raxone®, but due to alcoholism. There were 46 side effects from test results related to liver function, and 29 side effects related to abnormal blood count. These were reported in 36 patients. Twenty-seven patients experienced serious side effects. All of the safety data from this study was analyzed in detail. Overall, Raxone® was safe and well-tolerated in LHON patients enrolled in this study.REC name
North East - Newcastle & North Tyneside 1 Research Ethics Committee
REC reference
16/NE/0255
Date of REC Opinion
16 Sep 2016
REC opinion
Further Information Favourable Opinion