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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Eye Diseases; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Retinitis; Eye Diseases, Hereditary; Retinal Dystrophies
• Intervention / Treatment: Biological: Gene Therapy product-MCO-010

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 18

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: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study population will be comprised of the 18 adult subjects with advanced retinitis pigmentosa, previously dosed with MCO-010 in the RESTORE study.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observation of Participants exposed 1.2E11gc/eye of MCO-010; 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; Safety evaluation to monitor long term effects of previously injected MCO-010 in RP patients
Observation of Participants exposed to 0.9E11gc/eye of MCO-010; 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; Safety evaluation to monitor long term effects of previously injected MCO-010 in RP patients

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the long-term pharmacokinetic (PK) and pharmacodynamic (PD) impact of previous treatment with MCO-010 on gene reporter expression	PK parameters including change from baseline of fundus fluorescence intensity of reporter over time and PD correlation of gene expression with the efficacy measures in the study eye and fellow eye (selected sites)	156 Weeks

Collaborators and Investigators

• Sponsor: Nanoscope Therapeutics Inc.
• Investigators: Study Director: Samuel Barone, MD, Nanoscope Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Gene Therapy; Intravitreal Injections; Low Vision; Visual Acuity; AAV Vectors; Optogenetics; Multi-Characteristic Opsin; Multi-Luminance Y Mobility Test; Multi-Luminance Shape Discrimination Test
• Additional Relevant MeSH Terms: Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases; Retinitis; Retinitis Pigmentosa; Retinal Degeneration; Retinal Dystrophies; Eye Diseases, Hereditary
• Other Study ID Numbers: NTXLTFU-008

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 and results are analyzed. The results will be published on this site and be available to conference presentations and publications.
• IPD Sharing Time Frame: Within a year from the long term monitoring data availability
• IPD Sharing Access Criteria: IPD sharing access will be subject to data transfer agreement. IPD generated as part of this clinical study may be subject to patient confidentiality.

Drug and device information, study documents

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