Gene Therapy for Retinitis Pigmentosa

(liMeliGhT Trial)

Recruiting at 14 trial locations

Overseen By Eduardo Navajas, M.D

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Ocugen

Disqualifiers: Glaucoma, Retinal detachment, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a Phase 3 study to Assess the Efficacy, Safety and Tolerability of OCU400 in patients with retinitis pigmentosa (RP) associated with RHO mutations and patients with any other RP associated mutation with a clinical phenotype of RP. This is a multicenter, assessor blinded and randomized study which will enroll 150 subjects.

Do I need to stop my current medications for the trial?

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

Is gene therapy for retinal diseases generally safe in humans?

Gene therapy using AAV vectors for retinal diseases like Leber congenital amaurosis has been shown to be safe in humans, with no serious adverse events related to the vector reported up to 1.5 years after treatment. ^{1 2 3 4 5}

How is the treatment OCU400 for retinitis pigmentosa different from other treatments?

OCU400 is a gene therapy that uses an adeno-associated virus (AAV) to deliver a specific gene (NR2E3) to the retina, aiming to restore vision by targeting the underlying genetic cause of retinitis pigmentosa, which is different from other treatments that may not address the genetic root of the condition. ^{2 3 4 6 7}

Research Team

Huma Qamar

Principal Investigator

Ocugen

Eligibility Criteria

This trial is for individuals with Retinitis Pigmentosa, specifically those with RHO mutations or other RP-associated mutations. It's a large study involving multiple centers and will include 150 participants.

Inclusion Criteria

I am 8 years old or older.

Visual field of >5° in any meridian as measured by a III4e isopter or equivalent

Presence of photoreceptors as determined by SD-OCT

Exclusion Criteria

Breast-feeding, pregnancy, sperm donation or inability to practice strict contraception

Subject lacks evidence of outer nuclear layer

Absence of large regions of sensitivity in the pericentral and peripheral retinal regions

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a sequential, bilateral sub-retinal injection of OCU400 gene therapy

52 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits to assess long-term outcomes

Open-label extension (optional)

Control group subjects receive OCU400 subretinal injection after completion of 12-month follow-up

Long-term

Treatment Details

Interventions

• OCU400 (Gene Therapy)

Trial Overview The trial is testing the efficacy, safety, and tolerability of OCU400 gene therapy administered under the retina. The study design involves randomly assigning patients to receive this treatment while keeping assessors blind to who receives what.

Participant Groups

Group I: RHO Arm Experimental Treatment 1 Intervention

Subjects will receive a sub-retinal injection of OCU400-301 modifier gene therapy product with a concentration of 2.5 x 10E10 vg/eye

Group II: Gene Agnostic Arm Experimental Treatment 1 Intervention

Subjects will receive a sub-retinal injection of OCU400-301 modifier gene therapy product with a concentration of 2.5 x 10E10 vg/eye

Group III: Control for Gene Agnostic Arm Active Control 1 Intervention

Will not receive any active study intervention

Group IV: Control for RHO Arm Active Control 1 Intervention

Will not receive any active study intervention

OCU400 is already approved in Canada for the following indications:

Approved in Canada as OCU400 for:

• Retinitis Pigmentosa (Phase III clinical trial)

Who Is Running the Clinical Trial?

Ocugen

Lead Sponsor

Trials

12

Recruited

1,100+

Findings from Research

Human gene therapy using the rAAV2 vector for treating RPE65-related Leber congenital amaurosis was found to be safe, with no serious adverse events reported in young adult subjects up to 12 months after treatment.

Patients showed sustained improvements in visual sensitivity from 3 months to 12 months post-treatment, indicating the long-term efficacy of the gene therapy in enhancing vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Cideciyan, AV., Hauswirth, WW., Aleman, TS., et al.[2022]

In a phase 3 trial involving 31 participants with RPE65-mediated inherited retinal dystrophy, the gene therapy voretigene neparvovec significantly improved functional vision, as measured by multi-luminance mobility testing (MLMT), with an average improvement of 1.8 light levels compared to only 0.2 in the control group.

The treatment was found to be safe, with no serious adverse events related to the therapy, and 65% of participants in the intervention group achieved maximum improvement at the lowest luminance level tested, indicating a strong potential for restoring vision in previously untreatable cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Russell, S., Bennett, J., Wellman, JA., et al.[2022]

The study evaluated a gene replacement therapy using a specific rAAV2/4 vector to deliver the RPE65 gene in RPE65-deficient Briard dogs, showing restoration of vision and photoreceptor function within 15 days post-injection, with maximal function achieved by 3 months.

Safety assessments indicated retinal abnormalities post-treatment, but overall retinal function remained stable, highlighting the importance of early intervention as the 30-month-old dog did not recover vision, suggesting a critical therapeutic window for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Le Meur, G., Stieger, K., Smith, AJ., et al.[2021]

Gene replacement therapy using a specific rAAV2/4 vector successfully restored vision in RPE65-deficient Briard dogs, with significant improvements in rod and cone photoreceptor function observed as early as 15 days post-injection and stable results up to 11 months later.

The study indicates a potential therapeutic window for effective treatment, as younger dogs (8 to 11 months) showed restored vision, while an older dog (30 months) did not recover retinal function, highlighting the importance of age in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapeutic prospects in early onset of severe retinal dystrophy: restoration of vision in RPE65 Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Rolling, F., Le Meur, G., Stieger, K., et al.[2019]

Gene therapy using AAV vectors to deliver the RPE65 gene has been shown to be safe and effective for treating Leber's congenital amaurosis (LCA), with positive effects on retinal and visual function lasting at least 1.5 years in patients.

The treatment did not trigger significant immune responses against the RPE65 protein, indicating that AAV-mediated gene transfer can maintain its therapeutic effects without causing harm to the retinal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Simonelli, F., Maguire, AM., Testa, F., et al.[2022]

Voretigene neparvovec-rzyl (VN) gene therapy for RPE65 mutation-associated inherited retinal dystrophy showed durable improvements in navigational ability and light sensitivity, with benefits lasting up to 4 years after treatment in a study involving 40 subjects.

The safety profile of VN therapy was consistent with the procedures used, showing no harmful immune responses, indicating it is a safe option for patients with this degenerative eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials. Maguire, AM., Russell, S., Wellman, JA., et al.[2020]

Gene therapy using voretigene neparvovec-rzyl (VN) showed significant improvement in visual acuity, visual field, and light sensitivity in a 30-year-old female patient with early onset retinitis pigmentosa due to RPE65 mutation, three months after treatment.

The treatment was found to be safe, with no adverse effects reported, indicating that gene therapy can be an effective option for patients with advanced RPE65-associated retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa. Kwak, JJ., Kim, HR., Byeon, SH.[2022]

References

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

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. [2021]

4. Belgium pubmed.ncbi.nlm.nih.gov

Gene therapeutic prospects in early onset of severe retinal dystrophy: restoration of vision in RPE65 Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. [2019]

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

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. [2022]

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

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials. [2020]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa. [2022]