Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of a single intravitreal injection of virally-carried Multi-Characteristic Opsin (MCO-010).

Detailed Description
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This multicenter, randomized, double-masked, sham-controlled, dose-ranging study will evaluate 2 dose levels of MCO-010 in up to 18 subjects with retinitis pigmentosa (9 per dose). Nine subjects will receive sham injection. Subjects with a confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination, dilated fundus examination, and genetic testing will be considered for participation in this study. All subjects will continue to be assessed for 52 weeks following treatment with MCO-010.

Official Title
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A Phase 2b Randomized, Double-Masked, Sham-Controlled, Study to Evaluate the Efficacy and Safety of Intravitreal Injection of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]

Conditions
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Retinitis Pigmentosa, Retinitis, Retinal Diseases, Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Degeneration

Intervention / Treatment
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* Biological: Gene Therapy Product-MCO-010
* Procedure: Sham Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject population includes subjects with advanced RP. Subjects are eligible to be included in the study only if all of the following criteria apply: Age ≥ 18 years Able to comprehend and give informed consent. Confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination, dilated fundus examination, and genetic testing. Best-Corrected (Freiburg) Visual Acuity worse than 1.9 LogMAR (Snellen equivalent 20/1600, Count Fingers/ Hand Motion) in the study eye and no better than 1.6 LogMAR (Snellen equivalent 20/800) in the fellow eye during screening. Presence of retinal inner nuclear and nerve fiber layers on optical coherence tomography (OCT) testing in the study eye during screening as determined by the Investigator and confirmed by the Sponsor or designee. Exclusion Criteria: Subjects are excluded from the study if any of the following criteria apply: Prior participation in gene therapy program Individuals who refuse or are incapable of performing mobility testing or pass the mobility testing at 0.3 or 1 lux as determined by the Investigator and confirmed by the Sponsor or designee during screening, will be excluded. Presence of an active implantable medical device Pre-existing conditions in the study eye such as glaucoma, diseases affecting the optic nerve causing significant visual field loss, active uveitis, corneal or lenticular opacities). Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function. Subjects who are positive for syphilis, hepatitis B, C, and human immunodeficiency virus (HIV) will be excluded. Subjects who have undergone ocular surgery in the study eye within three months prior to Day 0. Presence of narrow iridocorneal angles contraindicating pupillary dilation in the study eye. Presence of disorders of the ocular media in the study eye which could interfere with visual acuity and other ocular assessments, including OCT, during the study period. Presence of vitreo-macular adhesion or traction, epiretinal membrane, macular pucker and macular hole in the study eye, evident by ophthalmoscopy and/or by OCT examinations and assessed by the investigator to significantly affect central vision. Current evidence of retinal detachment in the study eye that significantly affects central vision. Current use of hydroxychloroquine, chloroquine, or any related retina-toxic compounds. Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis. Having received retinal prothesis (such as ARGUS-II) or any gene or stem cell therapy (ocular or non-ocular).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Following a 1:1:1 block randomization schema, 9 subjects will be enrolled in each MCO-010 treatment group, and 9 subjects will be enrolled in the sham-controlled group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCO-010- High Dose<br>Participants receive 1.2E11gc/eye of MCO-010 | Biological: Gene Therapy Product-MCO-010<br>* The MCO-010 is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette<br>|
| Experimental: MCO-010- Medium Dose<br>Participants receive 0.9E11gc/eye of MCO-010 | Biological: Gene Therapy Product-MCO-010<br>* The MCO-010 is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette<br>|
| Sham Comparator: Sham Injection<br>Participants receive sham injection | Procedure: Sham Injection<br>* Sham Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of a single intravitreal injection of Multi-Characteristic Opsin (MCO-010) assessed by Multi Luminance Y- Mobility Test. | Change from Baseline in Multi Luminance Y-Mobility Test (MLYMT) score for the study eye at week 52 | 100 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects with MLYMT Scores | Proportion of subjects with MLYMT scores of 2 or more light level improvement at week 52 using the study eye | 100 weeks | 
| Proportion of Subjects with MLSDT Scores | Proportion of subjects with Multi-Luminance Shape Discrimination Test (MLSDT) scores of 2 or more light level improvements at week 52 using the study eye | 100 weeks | 
| Change from baseline in MLYMT score | Change from baseline in the MLYMT score at Week 52 when using both eyes | 100 weeks | 
| Change from Baseline in MLYMT score | Change from baseline in MLYMT at Weeks 16, 24, 36, 52, 76 and 100 | 100 weeks | 
| Proportion of MLYMT responders to treatment | Proportion of MLYMT responders to treatment at Weeks 16, 24, 36, 52, 76 and 100 | 100 weeks | 
| Effect of MCO-010 as assessed by static shape recognition assay | Change from baseline in accuracy in determination of 3-dimensional shapes using the MLSDT at Weeks 16, 24, 36, 52, 76 and 100 | 100 Weeks | 
| Proportion of MLSDT responders to treatment | Proportion of MLSDT responders to treatment at Weeks 16, 24, 36, 52, 76 and 100 | 100 weeks | 
| Effect of MCO-010 as assessed by Freiburg Visual Acuity | Change from baseline in Freiburg Visual Acuity (quantitative LogMAR score) at Weeks 16, 24, 36, 52, 76 and 100 | 100 Weeks | 
| To evaluate the effect of MCO-010 on visual field | Change from baseline in Visual Fields measured by Humphrey 30-2 perimetry at Weeks 16, 36, 52, 76 and 100 | 100 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinitis Pigmentosa, Eye Diseases Hereditary, Eye Diseases, Retinal Degeneration, Inherited Retinal Diseases, Rod & cone dystrophies, Optogenetics, Gene Therapy, AAV vectors, Intravitreal Injections, Low Vision, Multi-Characteristic Opsin, No Light Perception, Low-Vision Multi-Parameter Test (LVMPT)