A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and tolerability of bilateral subretinal delivery of adeno-associated virus vector with a serotype 5 capsid human rhodopsin kinase promoter. retinitis pigmentosa guanosine triphosphatase regulator (AAV5-hRKp.RPGR).

Official Title
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Phase 3 Study to Evaluate the Safety and Efficacy of AAV5-hRKp.RPGR for the Treatment of Japanese X-linked Retinitis Pigmentosa Associated With Pathogenic Variants in Retinitis Pigmentosa GTPase Regulator (RPGR)

Conditions
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X-Linked Retinitis Pigmentosa

Intervention / Treatment
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* Genetic: AAV5-hRKp.RPGR
* Genetic: AAV5-hRKp.RPGR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed as X-linked retinitis pigmentosa (XLRP) (generalized rod-cone dystrophy) associated with pathogenic or likely pathogenic variants in the retinitis pigmentosa guanosine triphosphatase regulator(RPGR) gene Has evidence of preserved retinal function as defined by a mean retinal sensitivity of greater than or equal to (>=) 2 decibel (dB) by Octopus static perimetry and evidence of preserved outer retinal structure (namely the presence of discernible ellipsoid zone) as determined by spectral domain-optical coherence tomography (SD-OCT) in both eyes Otherwise, healthy participant on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel or hematology outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator Exclusion Criteria: Has had ocular surgery within 3 months prior to screening or is anticipated to require ocular surgery within 6 months after the AAV5-hRKp.RPGR administration Is unable to perform the imaging assessments as required (for example: reliable static perimetry [reliability factor less than or equal to {<=}19], optical coherence tomography [OCT], or fundus autofluorescence [FAF]). Any investigational ocular treatment or any other ocular treatment that could confound the interpretation of the efficacy results or affect participant compliance with the visit schedule

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: AAV5-hRKp.RPGR Low Dose<br>Participants will receive bilateral subretinal administration of AAV5-hRKp.RPGR low dose, with surgical delivery to the 2 eyes performed within 7 to 21 days apart. | Genetic: AAV5-hRKp.RPGR<br>* AAV5-hRKp.RPGR will be administered by subretinal injection using a standardized surgical procedure.<br>|
| Experimental: Group 2: AAV5-hRKp.RPGR High Dose<br>Participants will receive bilateral subretinal administration of AAV5 hRKp.RPGR high dose, with surgical delivery to the 2 eyes performed within 7 to 21 days apart. | Genetic: AAV5-hRKp.RPGR<br>* AAV5-hRKp.RPGR will be administered by subretinal injection using a standardized surgical procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Event (AEs) | An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. | Up to 60 Months | 
| Number of Participants with Abnormalities in Clinical Laboratory Assessments | Number of participants with abnormalities in clinical laboratory assessment (hematology and serum chemistry) will be reported. | Up to 60 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Retinal Sensitivity Within the Central 10 Degrees Excluding Scotoma (MRS10) in Static Perimetry | Mean retinal sensitivity within the central 10 degrees excluding scotoma (MRS10) in static perimetry will be reported. | At Week 52 | 
| Change In Retinal Sensitivity by Pointwise Comparison in Full Visual Field at Week 52 | Change in retinal sensitivity by pointwise comparison in full visual field at Week 52 will be reported. | At Week 52 | 
| Change in Retinal Sensitivity by Pointwise Comparison in the Central 30 Degrees Visual field at Week 52 | Change in retinal sensitivity by pointwise comparison in the central 30 degrees visual field at Week 52 will be reported. | At Week 52 | 
| Mean Retinal Sensitivity Within the Full Visual Field Excluding Scotoma (MRS90) in Static Perimetry at Week 52 | Mean retinal sensitivity within the full visual field excluding scotoma (MRS90) in static perimetry at Week 52 will be reported. | At Week 52 | 
| Low Luminance Questionnaire (LLQ) in Patient Reported Outcome - Extreme Lighting Domain score at Week 52 | LLQ in patient reported outcome - extreme lighting domain score at Week 52 will be reported. | At Week 52 | 
| Low Luminance Visual Acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Letter Score in Binocular Assessment at Week 52 | Low luminance visual acuity by ETDRS chart score in binocular assessment at Week 52 will be reported. | At Week 52 | 
| Best Corrected Visual Acuity (BCVA) by ETDRS Chart Letter Score in Binocular Assessment at Week 52 | BCVA by ETDRS chart letter score in binocular assessment at Week 52 will be reported. | At Week 52 |