A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa (liMeliGhT)

A Phase 3, Multi-Center, Randomized Study to Assess The Efficacy, Safety and Tolerability of Subretinal OCU400 Gene Therapy for the Treatment of Retinitis Pigmentosa

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 140 subjects. Study has completed enrollment of all 140 subjects.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Genetic: Sub-Retinal Administration of OCU400-301

Detailed Description

A total of one hundred and forty (140) RP participants will be enrolled in this study into RHO arm or Gene agnostic arm. RHO arm will only enroll participants with confirmed genetic diagnosis of mutation in RHO gene; whereas Gene Agnostic arm will enroll RP Participants based on clinical diagnosis of RP and a confirmed genetic diagnosis with a gene associated with RP.

Subjects in each arm will be randomized into treatment and control groups with a 2:1 ratio. Subjects in the treatment group will receive a sequential, bilateral sub-retinal injection of OCU400 if both eyes meet inclusion criteria. Control or untreated group subjects will receive OCU400 subretinal injection after completion of 12-month follow-up.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2H OC8
      • Calgary Retina Consultants
    • Edmonton, Alberta, Canada, T6G 3E1
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
      • The University of British Columbia
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H2W 1L4
      • Research Institute of the McGill University Health Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
  • California
    • La Jolla, California, United States, 92093
      • University of Southern Califormia
    • Los Angeles, California, United States, 90033
      • University of Southern California, Roski Eye Insitute
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Advanced Research, LLC.
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Eye Institute
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females ≥ 3 years of age
2. Confirmed genetic diagnosis of autosomal dominant RHO mutation with clinical diagnosis of RP
3. Clinical Diagnosis of Syndromic or Non-Syndromic RP with/without confirmed genetic diagnosis of any other RP associated mutation (except AD-NR2E3)
4. BCVA ≤ 80 letters and ≥25 letters as measured by an ETDRS chart
5. Visual field of >5° in any meridian as measured by a III4e isopter or equivalent
6. Able to perform a Luminance LDNA at certain light intensity at the Screening visit
7. Presence of photoreceptors as determined by SD-OCT

Exclusion Criteria:

1. Subject lacks evidence of outer nuclear layer
2. Previous treatment with a gene-therapy or cell therapy product or treatment with any investigational drug or ocular device within one year.
3. History of any corticosteroid contraindication, corticosteroid related IOP spikes or uncontrolled glaucoma.
4. Cataract surgery within 3 months. YAG capsulotomy within 1 month. Any other intraocular surgery within 6 months.
5. Active ocular/intraocular infection, any history of rhegmatogenous retinal detachment or Current retinal detachment or retinal implant.
6. Breast-feeding, pregnancy, sperm donation or inability to practice strict contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control for RHO Arm; Will not receive any active study intervention
No Intervention: Control for Gene Agnostic Arm; Will not receive any active study intervention
Experimental: RHO Arm; Subjects will receive a sub-retinal injection of OCU400-301 modifier gene therapy product with a concentration of 2.5 x 10^10 vg/eye	Genetic: Sub-Retinal Administration of OCU400-301; Sub-Retinal Administration of OCU400-301
Experimental: Gene Agnostic Arm; Subjects will receive a sub-retinal injection of OCU400-301 modifier gene therapy product with a concentration of 2.5 x 10^10 vg/eye	Genetic: Sub-Retinal Administration of OCU400-301; Sub-Retinal Administration of OCU400-301

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in functional vision from baseline to week 52 in pooled analysis when study eyes in treatment group were compared to study eyes in untreated control	Change in functional vision from baseline to week 52 in pooled analysis from retinitis pigmentosa subjects when study eyes in treatment group were compared to study eyes in untreated control, as measured by the ability of a study participant to navigate through a maze in Luminance Dependent Navigation Assessment (LDNA)	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with change in visual function in Gene Agnostic Arm as assessed by LLVA letter scores	Change in LLVA letter scores in Gene Agnostic Arm subjects will be compared to controls	52 weeks
Change in functional vision from baseline to week 52 in all the treated eyes from RP subjects (study eyes + fellow treated eyes) when compared to all the eyes (study eyes and fellow eyes) in untreated control group	Change in functional vision from baseline to week 52 in all the treated eyes from RP subjects (study eyes + fellow treated eyes) when compared to all the eyes (study eyes and fellow eyes) in untreated control group, as measured by the ability of a study participant to navigate through a maze in Luminance Dependent Navigation Assessment (LDNA).	52 weeks
Change from Baseline in visual function in patients with retinitis pigmentosa when treatment group were compared to untreated controls	Change from Baseline in visual function in patients with retinitis pigmentosa when treatment group were compared to untreated controls in all RP subjects, as assessed by binocular low luminance visual acuity when using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score at Week 52.	52 weeks
Change from baseline in LDNA Lux-level results in treated subjects when compared to the untreated controls	Change from baseline in LDNA Lux-level results in all RP subjects in treated subjects when compared to the untreated controls at weeks 12, 24, 36, and 52	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Patients Global Impression of Change (PGIC) score	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Change from baseline in Patients Global Impression of Change (PGIC) score.	52 weeks
Change from baseline in Best corrected visual acuity (BCVA) measured by ETDRS	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Change from baseline in Best corrected visual acuity (BCVA) measured by ETDRS.	52 weeks
Improvement in Low luminance deficit (LLD) from baseline measured by ETDRS	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Improvement in Low luminance deficit (LLD) from baseline measured by ETDRS.	52 weeks
Improvement in mean retinal sensitivity from baseline as measured by static perimetry in the 30-degree	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Improvement in mean retinal sensitivity from baseline as measured by static perimetry in the 30-degree.	52 weeks
Change from baseline in hyperfluorescent ring as measured by Wide field-FAF	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Change from baseline in hyperfluorescent ring as measured by Wide field-FAF.	52 weeks
Change from baseline in area of RP atrophy in macular region as measured by Wide field-FAF	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Change from baseline in area of RP atrophy in macular region as measured by Wide field-FAF.	52 weeks
Change from baseline in hypo autofluorescence assessments in peripheral retina as measured by Wide field-FAF	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by: Change from baseline in hypo autofluorescence assessments in peripheral retina as measured by Wide field-FAF.	52 weeks
Change from baseline in hyper autofluorescence assessments in peripheral retina as measured by Wide field-FAF	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by change from baseline in hyper autofluorescence assessments in peripheral retina as measured by Wide field-FAF.	52 weeks
Changes in the Ellipsoid zone area from baseline as measured by SD-OCT	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by changes in Ellipsoid zone area from baseline as measured by SD-OCT.	52 weeks
Changes in the outer segment length from baseline as measured by SD-OCT	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by changes in the outer segment length as measured by SD-OCT.	52 weeks
Changes in the outer segment volume from baseline as measured by SD-OCT	Evaluate the efficacy of OCU400 gene therapy in treatment group when compared to untreated controls (in pooled analysis from patients in RHO arm and gene agnostic arm) with Retinitis Pigmentosa through week 52 as indicated by changes in the outer segment volume from baseline as measured by SD-OCT.	52 weeks

Collaborators and Investigators

• Sponsor: Ocugen
• Investigators: Study Chair: Huma Qamar, Ocugen

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): February 12, 2027
• Study Completion (Estimated): February 12, 2027

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NR2E3; RP; Retinitis Pigmentosa; RHO; Modified Gene therapy; Subretinal Injection
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinitis Pigmentosa
• Other Study ID Numbers: OCU400-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No