OCU400 for Retinitis Pigmentosa

(OCU400 Trial)

Not currently recruiting at 8 trial locations

Overseen By Huma Qamar

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ocugen

Disqualifiers: Gene therapy, Intraocular surgery, Infections, others

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

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

Compensation: Varies

Number of Visits: 49

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OCU400, a gene therapy, for individuals with certain genetic types of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). These eye diseases can lead to vision loss. The trial aims to determine if OCU400 is safe and effective in improving vision for those with specific genetic mutations. Participants will either receive varying doses of OCU400 or join a natural history study to monitor their eye condition over time. Suitable candidates have RP or LCA with specific genetic mutations and face significant vision challenges in daily life. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to potentially benefit from this innovative therapy.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team 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, is generally safe and well-tolerated. In earlier studies, OCU400 was administered through a small injection under the retina and demonstrated promising safety results. These studies found that the treatment rarely caused serious side effects, making it a potential option for individuals with certain genetic eye conditions. While the treatment remains under investigation, these early findings suggest that OCU400 could be a safe choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for retinitis pigmentosa?

OCU400 is unique because it targets genetic mutations specifically linked with retinitis pigmentosa (RP), such as NR2E3 and RHO mutations, as well as CEP290 mutations related to Leber congenital amaurosis (LCA). Unlike current treatments that primarily manage symptoms or slow progression, OCU400 uses a gene therapy approach to potentially correct the underlying genetic causes of vision loss. Researchers are excited about this treatment because it offers a targeted approach that could restore vision rather than just delay degeneration. Additionally, OCU400's potential for long-lasting effects after a single administration sets it apart from existing therapies that require ongoing use.

What evidence suggests that OCU400 might be an effective treatment for retinitis pigmentosa?

Research has shown that OCU400 might help people with retinitis pigmentosa, a condition affecting the retina that can lead to vision loss. The treatment delivers a gene called NR2E3 to the retina, helping to maintain its health. In this trial, participants will receive different doses of OCU400 based on their genetic mutations. Previous studies demonstrated that OCU400 improved vision, with some patients able to read 10 more letters on an eye chart. This suggests that OCU400 could enhance eyesight in individuals with specific genetic types of retinitis pigmentosa. ^{1 2 3 4 6}

Who Is on the Research Team?

Huma Qamar, MD, MPH, CMI

Principal Investigator

Ocugen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain genetic mutations causing retinitis pigmentosa or Leber Congenital Amaurosis. Participants must have a specific level of visual impairment and be able to perform a mobility test in low light. They can't join if they're pregnant, breastfeeding, have had recent eye surgery, previous gene therapy, or any condition that might affect the study results.

Inclusion Criteria

Confirmed genetic diagnosis of biallelic autosomal recessive NR2E3 mutations for Subgroup 1, autosomal dominant NR2E3 mutation for Subgroup 2, or autosomal dominant RHO mutations for Subgroup 3.

For the sentinel subject of Cohort 1-3, BCVA ≤ 20/160 in the study eye or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in the study eye.

For non-sentinel subjects, BCVA ≤ 20/50 or visual field less than 20° in any meridian, as measured by a III4e isopter or equivalent in the study eye.

Exclusion Criteria

Breastfeeding, pregnancy, sperm donation, or inability to practice strict contraception within the Treatment Observation Period.

Any intraocular surgery within 6 months.

Active ocular/intraocular infection (e.g., conjunctivitis, keratitis, scleritis, endophthalmitis)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subretinal injection of OCU400 in the study eye

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Multiple visits over 48 weeks

Long Term Safety Follow Up

Participants are followed for additional safety monitoring

2 years

What Are the Treatments Tested in This Trial?

Interventions

• OCU400

Trial Overview The trial tests three doses (low, medium, high) of OCU400 on patients with retinitis pigmentosa and Leber Congenital Amaurosis to evaluate its safety and effectiveness. It includes an initial phase followed by a natural history study across multiple centers involving up to 124 subjects.

How Is the Trial Designed?

Group I: Second Eye Dosing Experimental Treatment 1 Intervention

Eligible RP participants will be dosed in the untreated fellow eye with a therapeutic dose used in Phase 3 study of OCU400 (1.0x10E11vg/mL in 250 μl ) and will be followed for an additional 48 weeks.

Group II: Phase 2 (High and Medium Dose) Experimental Treatment 2 Interventions

Following DSMB confirmation, adult RP subjects with Biallelic autosomal recessive NR2E3 mutations, autosomal dominant NR2E3 mutations, Autosomal dominant RHO mutations will receive a high dose concentration of OCU400 or LCA patients with CEP290 mutation will receive a medium dose concentration of OCU400.

Group III: Pediatric Arm Experimental Treatment 1 Intervention

Pediatric subjects will receive the medium dose concentration

Group IV: Cohort 3 (High Dose) Experimental Treatment 1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup

Group V: Cohort 2 (Mid Dose) Experimental Treatment 1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup

Group VI: Cohort 1 (Low Dose) Experimental Treatment 1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation or RHO mutations subgroup

Group VII: Adult Arm Experimental Treatment 2 Interventions

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup will receive a high dose concentration of OCU400 and LCA patients with CEP290 will receive a medium dose concentration of OCU400

Group VIII: Natural History Study (OCU400-104) Active Control 1 Intervention

A Prospective and Retrospective Natural History Study of RP and LCA: This is an observatory study for the prospective natural history of RP and LCA in adult and pediatric subjects. The study will also collect and review retrospective data and ophthalmology examination of natural history and progression of disease for all subjects starting with earliest timepoint on or after the date of their diagnosis of RP or LCA. Subjects will be seen up to a total of four times during the 12 months of the Observational Period, at baseline, 3 months, 6 months and 12 months. A total of up to 100 subjects will be enrolled in the study, including: Approximately 76 newly enrolled subjects consisting of 50 adult RP subjects, 6 adult LCA subjects, 20 pediatric RP/LCA subjects. Up to 24 subjects that reconsent from the OCU400-101 study (subjects from OCU400-101 will provide data on their untreated eye)

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

Novel engineered rAAV vectors, AAV2.GL and AAV2.NN, allow for efficient targeting of photoreceptors through less invasive intravitreal injections, showing widespread retinal transduction in mice, dogs, and non-human primates.

In a proof-of-concept study, intravitreal delivery of the Cnga3 gene using AAV2.GL successfully restored cone-specific protein expression and improved vision responses in a mouse model of achromatopsia, highlighting the potential of these vectors for treating blinding retinal dystrophies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders. Pavlou, M., Schön, C., Occelli, LM., et al.[2023]

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]

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]

In a study of 8 patients treated with the gene therapy voretigene neparvovec (VN), retinal atrophy was observed in all eyes, both within and outside the treated area, over a follow-up period of 6-24 months.

Despite the development of retinal atrophy, the functional vision outcomes remained stable, indicating that VN may provide lasting benefits even in the presence of atrophic changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec. Reichel, FF., Seitz, I., Wozar, F., et al.[2023]

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/NCT06388200

NCT06388200 | A Phase 3 Study Of OCU400 Gene ... 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 ...

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

Safety and Efficacy from Phase 1/2 Clinical Trial for Retinitis ... We report the safety and efficacy of OCU400 gene modifier therapy from the phase 1/2 clinical trial for NR2E3 and RHO associated RP (NCT05203939).

5. 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 ...

6. 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 ...