OCU400 for Retinitis Pigmentosa

(OCU400 Trial)

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

22 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment OCU400 for Retinitis Pigmentosa?

The research on similar gene therapies, like voretigene neparvovec for RPE65-related retinal dystrophy, shows potential benefits in improving vision and stabilizing the condition. These therapies use adeno-associated viral vectors, similar to OCU400, suggesting that OCU400 might also help in treating Retinitis Pigmentosa by delivering corrective genes to the retina. ^{1 2 3 4 5}

What makes the OCU400 treatment for Retinitis Pigmentosa unique?

OCU400 is unique because it uses a gene therapy approach with an adeno-associated virus (AAV) vector to deliver a specific gene directly to the retina, potentially offering a more targeted and long-lasting treatment for Retinitis Pigmentosa compared to traditional therapies. ^{5 6 7 8 9}

What is the purpose of this trial?

This trial tests OCU400, an eye injection, in patients with specific genetic mutations causing RP and LCA. The treatment aims to correct faulty genes to prevent vision loss.

Research Team

Huma Qamar, MD, MPH, CMI

Principal Investigator

Ocugen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Phase 2 (High Dose) Experimental Treatment 1 Intervention

Following DSMB confirmation, adult LCA subjects with CEP290 mutation will receive a medium dose concentration of OCU400.

Group II: Pediatric Arm Experimental Treatment 1 Intervention

Pediatric subjects will receive the medium dose concentration and will have subjects with RP and LCA

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

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup and LCA patients with CEP290

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

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

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

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

Group VI: Adult Arm Experimental Treatment 1 Intervention

Biallelic autosomal recessive NR2E3 mutations subgroup or Autosomal dominant NR2E3 mutation, RHO mutations subgroup and LCA patients with CEP290

Group VII: 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+

Findings from Research

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]

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]

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]

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]

References

1. 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]

2. 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]

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

Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis. [2022]

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

Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Development of an optimized AAV2/5 gene therapy vector for Leber congenital amaurosis owing to defects in RPE65. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders. [2023]

7. 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]

8. 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]

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

Gene Supplementation in Mice Heterozygous for the D477G RPE65 Variant Implicated in Autosomal Dominant Retinitis Pigmentosa. [2023]