Gene Therapy for Retinitis Pigmentosa

(RESTORE Trial)

No longer recruiting at 6 trial locations

Overseen By Kristen Peterson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nanoscope Therapeutics Inc.

Disqualifiers: Glaucoma, Malignancies, Uveitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new gene therapy for individuals with Retinitis Pigmentosa (RP), a condition that can cause severe vision loss. The study will assess the safety and effectiveness of a single injection of a treatment called MCO-010. Participants will receive either a low dose, a high dose, or a placebo (a harmless injection with no active treatment). This trial suits those with advanced RP who have poor vision in both eyes and have not tried other gene therapies. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in RP treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MCO-010, a new treatment being tested for retinitis pigmentosa, has been studied in several trials. These studies found that MCO-010 is generally safe for participants. For instance, one study followed patients for up to three years and found that their vision improved without any serious safety problems.

The treatment uses gene therapy, which aims to fix or replace faulty genes. In the trials, patients received different amounts of MCO-010, but both low and high doses improved vision and did not cause major side effects. This suggests the treatment is safe for humans, at least in the doses tested so far.

This is a Phase 2 trial, meaning the treatment has already passed initial safety tests. While more research is needed to confirm long-term safety, the current results are promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MCO-010 and vMCO-010 for retinitis pigmentosa because they offer a novel approach through gene therapy, potentially addressing the root cause of vision loss by delivering genetic material directly to the eye. Unlike current treatments, which mainly focus on managing symptoms or slowing progression, these investigational therapies aim to restore function by targeting specific genetic defects. The gene therapy is delivered in varying doses (low and high) directly into the eye, which optimizes the potential for personalized treatment based on patient needs. This innovative mechanism could lead to significant breakthroughs in preserving and potentially improving vision for those affected by this challenging condition.

What evidence suggests that this trial's treatments could be effective for retinitis pigmentosa?

Research shows that MCO-010, a new therapy using light-sensitive proteins, has potential in treating retinitis pigmentosa, a condition that leads to vision loss. Studies have found that patients experienced noticeable improvements in their vision, lasting up to three years. Participants reported better sight, with some seeing up to three lines better on vision tests. MCO-010 uses a harmless virus to deliver a special protein to the eyes, enhancing their response to light. This therapy is unique because it can work regardless of the specific genetic cause of the disease, making it potentially helpful for many people. Overall, the treatment has proven safe and effective over time.

In this trial, participants will receive either a low dose or high dose of MCO-010, or a sham injection as a comparator. ^{1 2 3 4 5}

Who Is on the Research Team?

Dr Samarendra Mohanty

Principal Investigator

Nanoscope Therapeutics Inc.

Are You a Good Fit for This Trial?

Adults over 18 with advanced Retinitis Pigmentosa (RP) and very poor vision can join this trial. They must have a confirmed diagnosis of RP, some remaining retinal layers visible on OCT scans, and understand the study to give consent. Excluded are those with other eye diseases like glaucoma, recent eye surgery, or infections like HIV; those who've had gene therapy before; or cannot perform mobility tests.

Inclusion Criteria

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.

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.

I understand the study details and agree to participate.

Exclusion Criteria

I have not had eye surgery in the study eye within the last 3 months.

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.

My study eye does not have glaucoma, significant vision loss, active inflammation, or cloudiness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of MCO-010 or sham injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 weeks

Multiple visits at Weeks 16, 24, 32, 52, 76, and 100

What Are the Treatments Tested in This Trial?

Interventions

• MCO-010
• Sham Injection
• vMCO-010

Trial Overview The trial is testing MCO-010 optogenetic therapy involving one injection into the eye compared to a sham procedure. It aims to see if this gene therapy product can safely improve vision in people with severe visual impairment due to RP.

How Is the Trial Designed?

Group I: MCO-010- Low Dose Experimental Treatment 1 Intervention

Participants receive 0.9E11gc/eye of MCO-010

Group II: MCO-010- High Dose Experimental Treatment 1 Intervention

Participants receive 1.2E11gc/eye of MCO-010

Group III: Sham Injection Placebo Group 1 Intervention

Participants receive sham injection

Who Is Running the Clinical Trial?

Nanoscope Therapeutics Inc.

Lead Sponsor

Trials

8

Recruited

140+

Published Research Related to This Trial

Gene therapy using AAV vectors successfully restored the expression of the CNGB1a protein in a mouse model of retinitis pigmentosa, leading to the formation of functional CNG channels and preservation of retinal structure.

The treated mice showed significant improvements in retinal function and behavior, indicating that this gene therapy approach could be a promising treatment for rod channelopathy-associated retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Koch, S., Sothilingam, V., Garcia Garrido, M., et al.[2012]

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

The study demonstrated successful vision restoration in animal models of retinal degeneration using a new opsin called MCO1, delivered via a safe viral method, which significantly improved visually guided behavior.

MCO1 showed effectiveness at much lower light intensities compared to traditional opsins, suggesting it could be a promising gene therapy for various retinal diseases without compromising retinal cell viability under chronic light exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. Wright, W., Gajjeraman, S., Batabyal, S., et al.[2020]

Over the past 20 years, various proof-of-concept gene therapy studies have been conducted for autosomal dominant retinitis pigmentosa caused by mutations in the rhodopsin gene, showcasing different approaches and strategies.

The review compiles significant results from these studies, highlighting advancements in gene silencing and delivery methods that could lead to potential treatments for this form of retinal degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa. Sudharsan, R., Beltran, WA.[2020]

The study demonstrated successful vision restoration in animal models of retinal degeneration using a new opsin called MCO1, delivered via a safe viral method, which significantly improved visually guided behavior.

MCO1 showed effectiveness at much lower light intensities compared to traditional opsins, suggesting it could be a promising gene therapy for various retinal diseases without compromising retinal cell viability under chronic light exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. Wright, W., Gajjeraman, S., Batabyal, S., et al.[2022]

Citations

1. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00362-1/fulltext

Safety and efficacy of MCO-010 optogenetic therapy in ... Indeed, a durable treatment effect of MCO-010 has been observed in retinitis pigmentosa subjects up to a 3-year follow-up (NCT06162585). Despite ...

2. healio.com healio.com/news/ophthalmology/20250911/durable-efficacy-safety-seen-at-3-years-for-mco010-gene-therapy-in-retinitis-pigmentosa

Three-year data show durable efficacy, safety of MCO-010 MCO-010 for retinitis pigmentosa is showing promise in restoring vision. · It is the first gene-agnostic and mutation-agnostic gene therapy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12288717/

The effectiveness and value of sonpiretigene isteparvovec ... Nanoscope Therapeutics announces positive top-line results from randomized controlled trial of MCO-010 for retinitis pigmentosa. Accessed February 6, 2025 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04945772

Efficacy and Safety of MCO-010 Optogenetic Therapy in ... 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 ...

5. nanostherapeutics.com nanostherapeutics.com/2025/10/22/nanoscope-therapeutics-announces-durable-3-year-vision-improvements-from-remain-study-of-mco-010-in-retinitis-pigmentosa/

Nanoscope Therapeutics Announces Durable 3-Year ... REMAIN results showed sustained, 3-line vision gains vs baseline through 152 weeks for MCO-010 in patients having severe vision loss from ...