Efficacy and Safety of MCO-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: May 31, 2023
• 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 (MCO-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-MCO-010; Procedure: Sham Injection	Phase 2

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). 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.

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 MCO-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 MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
• Actual Study Start Date: July 13, 2021
• Actual Primary Completion Date: March 28, 2023
• Estimated Study Completion Date: March 1, 2024

Arms and Interventions

Arm	Intervention/treatment
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- Medium 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
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 Multi-Characteristic Opsin (MCO-010) assessed by Multi Luminance Y- Mobility Test. [ Time Frame: 100 weeks ]
   Change from Baseline in Multi Luminance Y-Mobility Test (MLYMT) score for the study eye at week 52

Secondary Outcome Measures :

1. Proportion of Subjects with MLYMT Scores [ Time Frame: 100 weeks ]
   Proportion of subjects with MLYMT scores of 2 or more light level improvement at week 52 using the study eye
2. Proportion of Subjects with MLSDT Scores [ Time Frame: 100 weeks ]
   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
3. Change from baseline in MLYMT score [ Time Frame: 100 weeks ]
   Change from baseline in the MLYMT score at Week 52 when using both eyes
4. Change from Baseline in MLYMT score [ Time Frame: 100 weeks ]
   Change from baseline in MLYMT at Weeks 16, 24, 36, 52, 76 and 100
5. Proportion of MLYMT responders to treatment [ Time Frame: 100 weeks ]
   Proportion of MLYMT responders to treatment at Weeks 16, 24, 36, 52, 76 and 100
6. Effect of MCO-010 as assessed by static shape recognition assay [ Time Frame: 100 Weeks ]
   Change from baseline in accuracy in determination of 3-dimensional shapes using the MLSDT at Weeks 16, 24, 36, 52, 76 and 100
7. Proportion of MLSDT responders to treatment [ Time Frame: 100 weeks ]
   Proportion of MLSDT responders to treatment at Weeks 16, 24, 36, 52, 76 and 100
8. Effect of MCO-010 as assessed by Freiburg Visual Acuity [ Time Frame: 100 Weeks ]
   Change from baseline in Freiburg Visual Acuity (quantitative LogMAR score) at Weeks 16, 24, 36, 52, 76 and 100
9. To evaluate the effect of MCO-010 on visual field [ Time Frame: 100 Weeks ]
   Change from baseline in Visual Fields measured by Humphrey 30-2 perimetry at Weeks 16, 36, 52, 76 and 100

Other Outcome Measures:

1. Proportion of subjects demonstrating a ≥2 unit in either MLYMT or MLSDT Score [ Time Frame: 100 weeks ]
   Proportion of subjects demonstrating a ≥2 unit improvement from baseline in EITHER the MLYMT OR the MLSDT score at Week 52 in the study eye
2. To evaluate the effect of MCO-010 on the listed safety endpoints [ Time Frame: 100 weeks ]
   Incidences, nature, and severity of ocular and non-ocular treatment emergent adverse events (TEAEs), Serious Adverse Events (SAEs); intraocular inflammation graded through ocular exam; intraocular pressure and retinal thickness

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

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: May 31, 2023
• Last Verified: May 2023

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.:

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)

Additional relevant MeSH terms:

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