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

• ClinicalTrials.gov Identifier: NCT04945772
• Recruitment Status: Active, not recruiting
• First Posted: June 30, 2021
• Last Update Posted: July 15, 2022
• Sponsor: Nanoscope Therapeutics Inc.
• Information provided by (Responsible Party): Nanoscope Therapeutics Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Retinitis Pigmentosa; Retinitis; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration	Biological: Gene Therapy Product-vMCO-010; Procedure: Sham Injection	Phase 2

Detailed Description:

This multicenter, randomized, double-masked, sham-controlled, dose-ranging study will evaluate 2 dose levels of vMCO-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 vMCO-010.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Following a 1:1:1 block randomization schema, 9 subjects will be enrolled in each vMCO-010 treatment group, and 9 subjects will be enrolled in the sham-controlled group.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Treatment assignment will be unknown (or masked) to the study participants, the evaluating physician (non-injecting), outcomes assessor, the sponsor and its agents.
• Primary Purpose: Treatment
• Official Title: A Phase 2b Randomized, Double-Masked, Sham-Controlled, Study to Evaluate the Efficacy and Safety of Intravitreal Injection of vMCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
• Actual Study Start Date: July 13, 2021
• Estimated Primary Completion Date: March 1, 2023
• Estimated Study Completion Date: March 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Efficacy of a single intravitreal injection of virally-carried Multi-Characteristic Opsin (vMCO-010) assessed by Y- Mobility Test. [ Time Frame: 100 weeks ]
   Change from Baseline in Y-Mobility Test compared to week 52.
2. Type, severity, and incidence of ocular and systemic adverse events (AEs) [ Time Frame: 100 weeks ]
   Type, severity, and incidence of ocular and systemic adverse events (AEs), specifically those related to intravitreal injection of vMCO-010

Secondary Outcome Measures :

1. Effect of vMCO-010 as assessed by static shape recognition assay [ Time Frame: 100 Weeks ]
   Change from baseline compared to Week 52 in the % shape recognition accuracy, measured with Static Shape recognition assay, performed at different light intensities
2. Effect of vMCO-010 on determination of optical flow direction [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in accuracy determination of optical flow direction
3. Effect of vMCO-010 as assessed by Freiburg Visual Acuity [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in Freiburg Visual Acuity.
4. Effect of vMCO-010 on pupillary light reflex [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in the % change in pupil size.
5. Effect of vMCO-010 on light sensitivity [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in the Full-field Stimulus Threshold (FST).
6. To evaluate the effect of vMCO-010 on visual field [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in visual field measured by perimetry.
7. Effect of vMCO-010 on functional vision outcomes [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in activities of daily living using the National Eye Institute Visual Function Questionnaire-25. Each question has several responses scored on a scale from 0 to 5, 0 to 6, or 0 to 10, and the Values are calculated in percentages.
8. Pharmacokinetic (PK) impact of vMCO-010 on gene reporter expression [ Time Frame: 100 Weeks ]
   Change from baseline compared to week 52 in PK parameters including the rate of increase of fluorescence intensity of reporter measured by fluorescence funduscopy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

1. Age ≥ 18 years
2. Able to comprehend and give informed consent.
3. Confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination, dilated fundus examination, and genetic testing.
4. 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.
5. 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:

1. Prior participation in gene therapy program
2. 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.
3. Presence of an active implantable medical device
4. 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).
5. Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
6. Subjects who are positive for syphilis, hepatitis B, C, and human immunodeficiency virus (HIV) will be excluded.
7. Subjects who have undergone ocular surgery in the study eye within three months prior to Day 0.
8. Presence of narrow iridocorneal angles contraindicating pupillary dilation in the study eye.
9. 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.
10. 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.
11. Current evidence of retinal detachment in the study eye that significantly affects central vision.
12. Current use of hydroxychloroquine, chloroquine, or any related retina-toxic compounds.
13. Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
14. Having received retinal prothesis (such as ARGUS-II) or any gene or stem cell therapy (ocular or non-ocular).

Contacts and Locations

Locations

United States, California

Nanoscope Clinical Site

Beverly Hills, California, United States, 90211

United States, Florida

Nanoscope Clinical Site

Miami, Florida, United States, 33136

Nanoscope Clinical Site

Pensacola, Florida, United States, 32503

United States, North Dakota

Nanoscope Clinical Site

Fargo, North Dakota, United States, 58103

United States, Texas

Nanoscope Clinical Site

Houston, Texas, United States, 77030

Nanoscope Clinical Site

McAllen, Texas, United States, 78503

Puerto Rico

Nanoscope Clinical Site

Arecibo, Puerto Rico, 00612

Sponsors and Collaborators

Nanoscope Therapeutics Inc.

Investigators

• Study Chair: Dr. Samarendra Mohanty; Nanoscope Therapeutics Inc.

More Information

• Responsible Party: Nanoscope Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04945772
• Other Study ID Numbers: NTXMCO-002.
• First Posted: June 30, 2021
• Last Update Posted: July 15, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The results of the clinical trial will be made available when the study is completed. The results will be published on this site and be available to conference presentations and publications.
• Time Frame: 12 months after the study is completed
• Access Criteria: Efficacy and Safety Results

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nanoscope Therapeutics Inc.:

Optogenetics; Retinitis Pigmentosa; Eye Diseases Hereditary; Eye Diseases; Retinal Degeneration; Inherited Retinal Diseases; Rod & cone dystrophies; Gene Therapy; AAV vectors; Intravitreal Injections; Low Vision; Multi-Characteristic Opsin; No Light Perception; Low-Vision Multi-Parameter Test (LVMPT)

Additional relevant MeSH terms:

Eye Diseases; Retinitis; Retinitis Pigmentosa; Retinal Diseases; Retinal Degeneration; Retinal Dystrophies; Eye Diseases, Hereditary; Genetic Diseases, Inborn