Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study

Study Overview
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Brief Summary
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This study will be conducted following Good Clinical Practice (GCP) and International Conference on Harmonization (ICH) guidelines. Eligible subjects will be consented to return for scheduled study visits for this study following their completion in study NTXMCO-002 (RESTORE). They will not receive a second treatment with MCO-010 (or a repeated sham injection) in this study

Detailed Description
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This study is designed to follow subjects with Retinitis Pigmentosa (RP) previously enrolled in study NTXMCO-002 (RESTORE, NCT04945772). In that study, 18 of 27 enrolled subjects received MCO-010, an ambient light-activated, Multi-Characteristic Opsin (MCO) transgene in an adeno-associated virus serotype 2 (AAV2) vector via intravitreal injection (IVT) and 9 of 27 received a sham injection. Those who received the sham injection will not be continued in the long-term, follow-up study for drug safety. MCO-010 has the potential to restore vision irrespective of the underlying gene mutation, and because it is directed at bipolar retinal cells, intact photoreceptors are not required. Further details on MCO-010 and the underlying disease under investigation are included in the protocol for RESTORE and are not repeated herein. The current study is a non-interventional long-term safety follow-up of the subjects who completed RESTORE, in accordance with FDA guidance on recipients of human gene therapy products.

Official Title
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Long Term Follow-up for Subjects Who Previously Participated in the NTXMCO-002 RESTORE Study

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously enrolled in study NTXMCO-002 (RESTORE) Able to comprehend and give informed consent. Able to comply with testing and all protocol tests. Agree to participate for the full 3-year duration of follow-up to the best of their ability and barring any unforeseen circumstances. Exclusion Criteria: Not applicable. Subjects will be included in this study and will be consented after completion of all assessments at their final RESTORE study visit

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observation of Participants exposed 1.2E11gc/eye of MCO-010<br>This is a long-term follow-up observational study of participants who previously received 1.2E11gc/eye of MCO-010. No investigational product will be administered in this study. | Biological: Gene Therapy product-MCO-010<br>* Safety evaluation to monitor long term effects of previously injected MCO-010 in RP patients<br>|
| Observation of Participants exposed to 0.9E11gc/eye of MCO-010<br>This is a long-term follow-up observational study of participants who previously received 0.9E11gc/eye of MCO-010 No investigational product will be administered in this study. | Biological: Gene Therapy product-MCO-010<br>* Safety evaluation to monitor long term effects of previously injected MCO-010 in RP patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the long-term safety of previous treatment with a single intravitreal injection of MCO-010 | Delayed adverse events. Incidence, nature, and severity of selected adverse events (AEs); all serious adverse events (SAEs); all ocular AEs including intraocular inflammation graded through ocular exam; non-ocular AEs with a common terminology criteria for adverse events (CTCAE) grade of 3 or greater; AEs of special interest (AESIs) including new malignancies, new incidence or exacerbation of any pre-existing neurologic disorder or rheumatologic or other autoimmune disorder, new incidence of hematologic disorder or new infection regardless of suspected relatedness to treatment with MCO-010. | 156 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of long-term effects on visual acuity of previous treatment with a single intravitreal injection of MCO-010 | Change from baseline in BCVA over time in both eyes | 156 Weeks | 
| Evaluation of long-term effects on shape discrimination at multiple light levels of previous treatment with a single intravitreal injection with MCO-010 | Change from baseline in multi-luminance shape discrimination test (MLSDT) scores | 156 Weeks | 
| Evaluation of long-term effects on navigation/mobility at multiple light levels of previous treatment with a single intravitreal injection with MCO-010 | Change from baseline in multi-luminance Y-Mobility Test (MLYMT) score | 156 Weeks | 
| Exploration of the long-term impact of previous treatment with MCO-010 on retinal thickness and retinal anatomy | Assessment of fundus photography and Optical Coherence Tomography (OCT) outcomes over time | 156 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Therapy, AAV Vectors, Low Vision, Intravitreal Injections, Optogenetics, Multi-Characteristic Opsin, Multi-Luminance Y Mobility Test, Multi-Luminance Shape Discrimination Test, Visual Acuity