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Trial registered on ANZCTR


Registration number
ACTRN12621000826842
Ethics application status
Approved
Date submitted
14/05/2021
Date registered
28/06/2021
Date last updated
28/06/2021
Date data sharing statement initially provided
28/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Idebenone versus placebo in dominant optic atrophy
Scientific title
Phase II randomised, double blinded, placebo-controlled, proof-of-concept study of the efficacy of idebenone in dominant optic atrophy
Secondary ID [1] 304232 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dominant Optic Atrophy 321933 0
Mitochondrial Disease 321934 0
Condition category
Condition code
Neurological 319657 319657 0 0
Other neurological disorders
Eye 319658 319658 0 0
Diseases / disorders of the eye
Human Genetics and Inherited Disorders 319659 319659 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Idebenone in Dominant Optic Atrophy will be a placebo controlled trial, the intervention will include 20 participants with genetically confirmed OPA1 mutation who will receive idebenone 300mg by mouth Three times per day (900mg daily) for 12 months.
Adherence to intervention will be monitored by the clinical trials pharmacy by checking the number of capsules left at the visits that happen every three months during the intervention.
Intervention code [1] 320564 0
Treatment: Drugs
Comparator / control treatment
The control group will receive a placebo. The placebo will look identical to the active drug and be administered in the same fashion. The placebo will consist of a microcellulose capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 327531 0
Change from baseline in best-corrected visual acuity in the best eye using logMAR acuity in best eye.
Timepoint [1] 327531 0
12 months post-commencement of intervention.
Secondary outcome [1] 395537 0
Change from baseline in best corrected visual acuity in both eyes with eyes considered as independent {logMAR chart}
Timepoint [1] 395537 0
12 months post-commencement of intervention.
Secondary outcome [2] 395538 0
Change from baseline in scotoma size in both eyes with eyes considered as independent {Humphrey Field Analyser}.
Timepoint [2] 395538 0
at 12 months post-commencement of intervention.

Eligibility
Key inclusion criteria
(i) Dominant Optic Atrophy confirmed by pathogenic OPA1 mutation
(ii) Best-corrected visual acuity of logMAR 0.1 or worse in at least one eye
(iii) Primary cause of reduced visual acuity must be DOA/DOA plus
(iv) Aged 14 years to 85 years
Minimum age
14 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Pregnant women
(ii) Women planning to become pregnant during the course of the study
(iii) Women who are currently breastfeeding
(iv) eGFR < 30
(v) Elevations greater than 3 times the upper limit of normal of AST or ALT and/or cirrhosis
(vi) Lactose intolerance
(vii) Cognitive impairment that in the investigator’s opinion would render the participant unable to participate in the assessments
(viii) Weekly alcohol intake greater than 35 units for males or 24 units for females
(ix) Current drug abuse
(x) Participation in another clinical trial of any investigational drug within 3 months prior to baseline
(xi) Primary cause of reduced visual acuity is not DOA
(xii) History of amblyopia
(xiii) Unable to reliably perform HVF or OCT tests
(xiv) Other condition that in the investigator’s opinion is likely to interfere with the evaluation of the patient’s safety and of the study outcome.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified based on ‘best-corrected visual acuity". For the purposes of stratification ‘best-corrected visual acuity’ will be measured in each eye. The eye with the best ‘best-corrected visual acuity’ will be used for the purposes of stratification
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary purpose of this Phase II study is to assess the safety and an early proof of concept efficacy signal. The sample size of 25 to 40 subjects is a projection based on results of a study. This study provided results for the change from baseline in visual acuity in the right and left eyes separately at a mean of 7.4 and 16.4 months follow-up. Standard deviations for the changes from baseline in logMAR units ranged from 0.05 to 0.10.

To detect a difference of 0.15 logMAR units between the treatment groups in change in visual acuity from baseline after 12 months of treatment and assuming a standard deviation of 0.11 logMAR units, 10 patients per group are needed to achieve an 80% power using a two-sided significance level of 0.05. If the standard deviation increases to as much as 0.14 then 15 patients per group are needed.

To detect a difference of 0.15 logMAR units between the treatment groups in change in visual acuity from baseline after 24 months of treatment and assuming a standard deviation of 0.10 logMAR units, 10 patients per group are needed to achieve an 80% power using a two-sided significance level of 0.025 (this is lower than the usual 0.05 level to allow for the interim analysis see section 10.4). The standard deviation was estimated on a very small number of patients’ data and at slightly different timepoints to those used here. If the standard deviation increases to as much as 0.13 then 16 patients per group are needed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/07/2021
Actual
Date of last participant enrolment
Anticipated
14/07/2021
Actual
Date of last data collection
Anticipated
31/08/2022
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW
Recruitment hospital [1] 19454 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 34046 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 308610 0
Hospital
Name [1] 308610 0
The Department of Neurogenetics Royal North Shore Hospital
Country [1] 308610 0
Australia
Primary sponsor type
Hospital
Name
Northern Sydney Local Health District
Address
Reserve Road
Royal North Shore Hospital
St Leonards, NSW 2065
Country
Australia
Secondary sponsor category [1] 309477 0
None
Name [1] 309477 0
Address [1] 309477 0
Country [1] 309477 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308542 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 308542 0
Reserve Road
Royal North Shore Hospital
St Leonards, NSW 2065
Ethics committee country [1] 308542 0
Australia
Date submitted for ethics approval [1] 308542 0
03/06/2020
Approval date [1] 308542 0
13/07/2020
Ethics approval number [1] 308542 0

Summary
Brief summary
Patients with an OPA1 mutation inherit a condition called dominant optic atrophy (DOA) which causes vision loss over time. A medication called idebenone has been shown to decrease the vision loss in patients with a similar condition, called Leber's Hereditary Optic Neuropathy, and thus this trial will investigate whether similar results can be seen in patients with dominant optic atrophy. The study will be a blinded randomised placebo-controlled study. One arm of the study will include participants with DOA who will receive idebenone, and the second arm will include participants with DOA who will receive a placebo. At the end of 12 months, the groups will be investigated to see if there is a between group difference in the rate of visual decline.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111074 0
Dr Kate Ahmad
Address 111074 0
3E Clinical Admin
Dept of Neurology
2 Reserve Road
Royal North Shore Hospital
St Leonards, NSW 2065
Country 111074 0
Australia
Phone 111074 0
+61294631880
Fax 111074 0
+61294631058
Email 111074 0
[email protected]
Contact person for public queries
Name 111075 0
Kate Ahmad
Address 111075 0
3E Clinical Admin
Dept of Neurology
2 Reserve Road
Royal North Shore Hospital
St Leonards, NSW 2065
Country 111075 0
Australia
Phone 111075 0
+61294631880
Fax 111075 0
+61294631058
Email 111075 0
[email protected]
Contact person for scientific queries
Name 111076 0
Kate Ahmad
Address 111076 0
3E Clinical Admin
Dept of Neurology
2 Reserve Road
Royal North Shore Hospital
St Leonards, NSW 2065
Country 111076 0
Australia
Phone 111076 0
+61294631880
Fax 111076 0
+61294631058
Email 111076 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We have not consented for this


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11678Study protocol  [email protected]
11679Informed consent form  [email protected]



Results publications and other study-related documents

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