Gene Therapy for Retinitis Pigmentosa

(liMeliGhT Trial)

Recruiting at 17 trial locations

Overseen By Eduardo Navajas, M.D

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Ocugen

Disqualifiers: Glaucoma, Retinal detachment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy called OCU400 to determine its effectiveness for people with retinitis pigmentosa (RP), a vision-affecting condition. The trial seeks to evaluate the efficacy and safety of OCU400 for individuals with RP due to RHO mutations or other genetic causes. Participants will either receive the gene therapy or join a control group without treatment. Suitable candidates for this trial include those diagnosed with RP who experience vision difficulties, such as trouble seeing in low light. As a Phase 3 trial, this represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for RP.

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

Research has shown that OCU400, a gene therapy for treating retinitis pigmentosa (RP), was safe in earlier studies. Patients who received OCU400 experienced mild and manageable side effects, with no severe or unexpected problems. This indicates the treatment is generally well-tolerated. Although more information is needed to confirm these results, the current evidence is promising for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for retinitis pigmentosa?

Unlike standard treatments for retinitis pigmentosa, which often involve vitamin supplements or visual aids, OCU400 is a cutting-edge gene therapy. It works by delivering a modifier gene directly into the retina through a sub-retinal injection, targeting the underlying genetic causes of vision loss. Researchers are excited because this approach has the potential to restore or preserve vision by addressing the root cause of the disease, rather than just managing symptoms. This gene therapy could offer hope for patients with various genetic mutations responsible for retinitis pigmentosa, making it a potentially groundbreaking treatment.

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

Research has shown that OCU400, a gene therapy, may help treat retinitis pigmentosa (RP). In earlier studies, patients who received OCU400 demonstrated noticeable improvement in their vision, reading 10 more letters on a vision chart in dim light. This trial includes two experimental arms where participants will receive a sub-retinal injection of the OCU400-301 modifier gene therapy product. The therapy delivers a specific gene to the eye, helping it function normally again. Most side effects related to the surgery resolved over time. These results suggest that OCU400 could effectively improve vision for people with RP. ^{1 2 3 6 7}

Who Is on the Research Team?

Huma Qamar

Principal Investigator

Ocugen

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• OCU400

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.

How Is the Trial Designed?

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 United States, Canada for the following indications:

Approved in United States as OCU400 for:

• Expanded Access Program for Retinitis Pigmentosa

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924001257

SAFETY AND EFFICACY RESULTS FROM A PHASE 1/2 ... The OCU400 (AAV-hNR2E3) gene therapy offers a promising solution by delivering the nuclear hormone receptor NR2E3 to the retina to restore retinal homoeostasis.

2. ocugen.com ocugen.com/wp-content/uploads/2024/06/Poster-OCU400.pdf

2 Clinical trial of OCU400 modifier gene therapy for ... Safety and Efficacy results from a Phase 1/ 2 Clinical trial of OCU400 modifier gene therapy for treatment of retinitis pigmentosa. Sub-set analysis of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05203939

NCT05203939 | Study to Assess the Safety and Efficacy of ... This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU400 in patients with retinitis pigmentosa associated with NR2E3 and RHO mutations.

4. ocugen.gcs-web.com ocugen.gcs-web.com/news-releases/news-release-details/ocugen-inc-announces-positive-2-year-data-across-multiple

A Novel Modifier Gene Therapy for Retinitis Pigmentosa OCU400 demonstrated meaningful improvement of 2-line gain (10 letters on ETDRS chart) in low-luminance visual acuity (LLVA) in treated eyes when compared to ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2796216

Safety and Efficacy from Phase 1/2 Clinical Trial for Retinitis ... Results : 18 subjects were dosed and data from subjects who completed 6-months post dosing are reported. Most AE's were related to the surgery and resolved ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06388200

A Phase 3 Study Of OCU400 Gene Therapy for the ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12387042/

Genetic Therapies for Retinitis Pigmentosa - PubMed Central The Phase 1/2 open-label, multicenter clinical trial of OCU400 reported favorable preliminary safety outcomes. ... safety data pending; requires ...