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

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]

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).

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Retinitis; Eye Diseases, Hereditary; Retinal Dystrophies
• Intervention / Treatment: Procedure: Sham Injection; Biological: Gene Therapy Product-MCO-010

Detailed Description

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). An additional 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 100 weeks following treatment with MCO-010.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Nanoscope Clinical Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Nanoscope Clinical Site
  • Florida
    • Pensacola, Florida, United States, 32503
      • Nanoscope Clinical Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Nanoscope Clinical Site
  • Texas
    • Houston, Texas, United States, 77030
      • Nanoscope Clinical Site
    • McAllen, Texas, United States, 78503
      • Nanoscope Clinical Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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) in the study eye and no better than 1.6 LogMAR (Snellen equivalent 20/800) in the fellow eye during screening.

Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria apply:

1. Prior participation in gene therapy program
2. 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).
3. Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
4. Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
5. Having received retinal prothesis (such as ARGUS-II) or any gene or stem cell therapy (ocular or non-ocular).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of a single intravitreal injection of Multi-Characteristic Opsin (MCO-010) as assessed by best corrected visual acuity.	Change from Baseline in the Freiburg Visual Acuity (quantitative LogMAR) score for the study eye at Week 52.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of MCO-010 as assessed by best corrected visual acuity.	Change from Baseline in the Freiburg Visual Acuity (quantitative LogMAR) score for the study eye at Week 76.	Week 76
Efficacy of MCO-010 as assessed by mobility testing.	Change from Baseline in Multi-Luminance Y-Mobility Test score. Range: -1 to 5, higher score means better outcome.	Weeks 16,24,32,52,76,100
Efficacy of MCO-010 as assessed by mobility testing.	Proportion of subjects with Multi-Luminance Y-Mobility Test score scores of 2 or more light level improvement from Baseline. Range: 0% to100%, higher score means better outcome.	Weeks 16,24,32,52,76,100
Efficacy of MCO-010 as assessed by static shape recognition assay.	Proportion of subjects with Multi-Luminance Shape Discrimination Test scores of 2 or more light level improvements from Baseline. Range: 0% to 100%, higher score means better outcome.	Weeks 16,24,32,52,76,100
Efficacy of MCO-010 as assessed by static shape recognition assay.	Change from Baseline in Multi-Luminance Shape Discrimination Test score. Range: 0 to 5, higher score means better outcome.	Weeks 16,24,32,52,76,100
Efficacy of MCO-010 as assessed on visual field.	Change from Baseline in Visual Fields measured by Humphrey 30-2 perimetry.	Weeks 16,24,32,52,76,100

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of MCO-010 as assessed by a composite of functional assessments.	Proportion of subjects demonstrating a ≥2 unit improvement from Baseline in EITHER the MLYMT OR the MLSDT score at Week 52.	Week 52
Safety of MCO-010.	Incidences, nature, and severity of ocular and non-ocular treatment emergent adverse events (TEAEs).	100 weeks

Collaborators and Investigators

• Sponsor: Nanoscope Therapeutics Inc.
• Investigators: Study Chair: Dr Samarendra Mohanty, Nanoscope Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): January 18, 2024

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gene Therapy; Eye Diseases; Intravitreal Injections; Low Vision; Retinitis Pigmentosa; Visual Acuity; Retinal Degeneration; Inherited Retinal Diseases; Rod & cone dystrophies; Eye Diseases Hereditary; Optogenetics; AAV vectors; Multi-Characteristic Opsin; No Light Perception; Multi-Luminance Y Mobility Test (MLYMT); Multi-Luminance Shape Discrimination Test (MLSDT)
• Additional Relevant MeSH Terms: Retinal Diseases; Retinitis; Retinitis Pigmentosa; Eye Diseases; Genetic Diseases, Inborn; Retinal Degeneration; Retinal Dystrophies; Eye Diseases, Hereditary
• Other Study ID Numbers: NTXMCO-002.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: 12 months after the study is completed
• IPD Sharing Access Criteria: Efficacy and Safety Results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No