Gene Therapy for Retinitis Pigmentosa

(RESTORE Trial)

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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new eye injection that uses a virus to deliver a helpful protein to improve vision in patients with severe vision loss from Advanced Retinitis Pigmentosa.

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.

What data supports the effectiveness of the treatment MCO-010 for retinitis pigmentosa?

Research shows that using multicharacteristic opsin (MCO) in animal models with retinal degeneration led to significant vision improvement. The treatment was delivered safely to specific retinal cells and improved visually guided behavior, suggesting potential effectiveness for retinitis pigmentosa. ^{1 2 3 4 5}

Is gene therapy for retinitis pigmentosa safe for humans?

In a study on gene therapy for X-linked retinitis pigmentosa, the treatment was generally safe, with only some patients experiencing inflammation that responded to steroids. Another study in dogs showed that a similar gene therapy did not cause inflammation or immune reactions, suggesting it is safe. ^{1 4 6 7 8}

What makes the treatment MCO-010 for retinitis pigmentosa unique?

The treatment MCO-010 for retinitis pigmentosa is unique because it involves gene therapy, which aims to address the genetic cause of the disease by delivering a healthy copy of the gene directly to the retina, potentially offering a more targeted and long-lasting solution compared to traditional treatments that only manage symptoms. ^{1 7 9 10 11}

Research Team

Dr Samarendra Mohanty

Principal Investigator

Nanoscope Therapeutics Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Gene therapy for hereditary eye diseases: where are we?]. [2012]

3. United States pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Biodistribution of adeno-associated virus type 2 carrying multi-characteristic opsin in dogs following intravitreal injection. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa. [2020]

7. United States 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Development of a translatable gene augmentation therapy for CNGB1-retinitis pigmentosa. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. [2012]