Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON)
Conditions: Leber's Hereditary Optic Neuropathy (LHON)
Sponsor: Santhera Pharmaceuticals

 
Case Record Survey LHON  
SNT-CRS-002 synopsis 
 
Confidential 
 
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Case Record Survey  
 
Synopsis 
 
 
 
 
Historical Case Record Survey of Visual Acuity Data  
from Patients with  
Leber’s Hereditary Optic Neuropathy (LHON) 
 
 
Protocol Number: 
SNT-CRS-002 
Version: 
1.0 
Date: 
5 April 2016 
NCT number: 
NCT02796274 
 
 
 
 
Property of Santhera Pharmaceuticals (Switzerland) Limited 
 
 
 
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Ltd. Except as otherwise agreed to in writing, by accepting or reviewing this document, you agree to 
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applicable law) or use it for unauthorized purposes. In the event of any actual or suspected breach of 
this obligation, Santhera Pharmaceuticals (Switzerland) Ltd. must be promptly notified. 
 

 
Case Record Survey LHON  
SNT-CRS-002 synopsis 
 
Confidential 
 
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 Synopsis 
 
Survey Title 
Historical Case Record Survey (CRS) of Visual Acuity Data  from 
Patients with Leber’s Hereditary Optic Neuropathy (LHON) 
Disease 
Leber’s Hereditary Optic Neuropathy (LHON)   
Survey Objectives 
1. To establish the clinical course (natural history) and visual acuity 
(VA) outcomes in patients with a genetically confirmed diagnosis 
of LHON.  
2. To generate a natural history group of idebenone naive patients 
to serve as comparator group for the open-label study SNT-IV-
005 by combining data from this CRS and CRS data collected 
previously (as reported in SNT-IR-006, NCT01892943)  
Participating Sites 
CRS data will be collected from expert clinical study sites that maintain 
records of VA assessments for LHON patients that may participate in 
the SNT-IV-005 study and/or the Post Authorisation Safety Study 
(PASS; SNT-IV-003).  
Additionally, data collected in the previous CRS (SNT-IR-006) will be 
updated where possible by collecting subsequent VA assessments 
through chart abstraction.   
Survey Endpoints 
Primary endpoint: In eyes with a VA assessment made ≤1 year after the 
onset of symptoms 
1. Proportion of eyes with clinically relevant recovery of VA from 
Baseline or in which Baseline VA better than 1.0 logarithm of the 
minimal angle of resolution (logMAR) was maintained at 12 
months (primary time point)   
(where Baseline is the first VA assessment after onset of symptoms. At 
12 months (the primary time point) means the VA observation closest to 
12 months after Baseline within the window of 12±3 months) 
Secondary Endpoints: In eyes with a VA assessment made ≤1 year after 
the onset of symptoms  
1. Proportion of eyes with clinically relevant recovery of VA from 
Baseline at 12 months  
2. Proportion of eyes in which Baseline VA better than 1.0 logMAR 
was maintained at 12 months  
3. Proportion of patients with clinically relevant recovery of VA in at 
least one eye or in which Baseline VA better than 1.0 logMAR 
was maintained in at least one eye at 12 months 
4. Proportion of eyes/patients with “Off-chart” VA at Baseline in 
whom VA improves to better than or equal to 1.60 logMAR at 12 
months 

 
Case Record Survey LHON  
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5. Proportion of eyes/patients with VA in the categories of better 
than 1.0 logMAR, 1.0 to 1.68 logMAR and above 1.68 logMAR 
at Baseline, 12 months and 24 months 
6. Proportion of eyes with clinically relevant recovery of VA from 
Baseline or in which Baseline VA better than 1.0 logMAR was 
maintained at 24 months 
(where Baseline is the first VA assessment after onset of symptoms. At 
12 months (the primary time point) means the VA observation closest to 
12 months after Baseline within the window of 12±3 months. At 24 
months means the VA observation closest to 24 months after Baseline 
within the window of 24±3 months) 
Secondary Endpoints: In eyes with a VA assessment made >1 year after 
the onset of symptoms  
1. Proportion of eyes with clinically relevant recovery of VA from 
Baseline or in which Baseline VA better than 1.0 logMAR was 
maintained at 12 months  
2. Proportion of eyes with clinically relevant recovery of VA from 
Baseline at 12 months  
3. Proportion of eyes in which Baseline VA better than 1.0 logMAR 
was maintained at 12 months  
4. Proportion of patients with clinically relevant recovery of VA in at 
least one eye or in which Baseline VA better than 1.0 logMAR 
was maintained in at least one eye at 12 months 
5. Proportion of eyes/patients with “Off-chart” VA at Baseline in 
whom VA improves to better than or equal to 1.60 logMAR at 12 
months 
6. Proportion of eyes/patients with VA in the categories of better 
than 1.0 logMAR, 1.0 to 1.68 logMAR and above 1.68 logMAR 
at Baseline, 12 months and 24 months 
7. Proportion of eyes with clinically relevant recovery of VA from 
Baseline or in which Baseline VA better than 1.0 logMAR was 
maintained at 24 months 
(Where Baseline is any assessment made >1 year after onset of 
symptoms for which a follow-up VA assessment within 12±3 months is 
available. At 24 months means the VA observation closest to 24 months 
after any Baseline within the window of 24±3 months) 
Inclusion Criteria 
Case Records from patients will be collected from ALL patients of the 
participating sites who fulfil the following prospectively defined inclusion 
criteria: 
1. age ≥ 12 years 

 
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2. the onset of symptoms is dated after 1999 and is well 
documented (at least month of onset of symptoms is known for 
each eye) 
3. at least two VA assessments are available within 5 years of onset 
of symptoms and prior to idebenone use 
4. have a genetic diagnosis for LHON for one of the following 
mitochondrial DNA (mtDNA) mutations: G11778A, G3460A, 
T14484C 
Exclusion Criteria 
1. any participation in an interventional clinical trial after the onset 
of symptoms 
2. any other cause of visual impairment (e.g. glaucoma, diabetic 
retinopathy, AIDS related visual impairment, cataract, macular 
degeneration, etc.) or any active ocular disorder (uveitis, 
infections, inflammatory retinal disease, thyroid eye disease, 
etc.) during the data collection period 
Study Design 
A multi-country, multi-centre, historical case record survey which will 
collect data on the VA of eligible patients from existing medical records  
Number of patients  
Data will be collected from as many case records as possible during the 
case record survey collection period. A minimum of 89 eligible patients 
with onset of symptoms ≤1 year prior to Baseline is required for sufficient 
statistical power for comparison to perform the cross analysis with SNT-
IV-005 study. 
Statistical Methods 
Descriptive statistics will be used to analyse the data from this CRS. The 
primary analysis will be to describe the changes in VA from Baseline 
(see SNT-IV-005 study protocol for details), to the VA at 12 months after 
the Baseline (the primary time point) and at 24 months after Baseline.  
Data will be pooled with previously collected (and updated) CRS data 
(as reported in SNT-IR-006, NCT01892943) to allow comparison to the 
VA outcome of Raxone®- treated patients from the open-label study 
SNT-IV-005. 
Data to be collected 
• 
Month and year of birth 
• 
Gender 
• 
Results of genetic assessment of LHON specific mtDNA 
mutations 
• 
Relevant medical history  
• 
LHON history including date of onset of first symptoms (in each 
eye) 
• 
All VA test results available from date of onset until any use of 
idebenone 
• 
Method and eye chart used (e.g. ETDRS, Snellen, Counting 
Fingers etc.) for VA at each assessment 
• 
Idebenone use (date of first intake, date of stop/ongoing, dose)