Natural History of the Progression of X-Linked Retinitis Pigmentosa

Study Overview
=================
Brief Summary
-----------------
The objective of the study is to gain a better understanding of disease progression over time in participants with X-linked retinitis pigmentosa (XLRP).

Detailed Description
-----------------
This study was previously posted by NightstaRx Ltd. In October, 2020, sponsorship of the trial was transferred to Biogen.

Official Title
-----------------
Natural History of the Progression of X-Linked Retinitis Pigmentosa

Conditions
-----------------
X-Linked Retinitis Pigmentosa

Intervention / Treatment
-----------------
* Other: Other: Assessments


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Have documentation of a pathogenic mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. Are willing and able to undergo ophthalmic examinations, as required by protocol, for up to 24 months Have an ETDRS BCVA in at least 1 eye of ≥34 letters (Equivalent to Snellen ≥ 6/60 or 20/200; decimal 0.1; LogMAR 1.0). Mean retinal sensitivity in the eligible eye as assessed by microperimetry: Males with a mean retinal sensitivity of 68 loci ranging from ≥0.1 decibels (dB) and ≤20 dB. Females with a mean retinal sensitivity of 68 loci ranging from ≥0.1 dB and ≤25 dB. If female, have symptomatic disease with impairment of visual function. Key Exclusion Criteria: Have a history of amblyopia in the eligible eye. Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may put the participant at risk because of participation in the study, may influence the results of the study, may influence the participant's ability to perform study diagnostic tests, or impact the participant's ability to participate in the study. This includes clinically significant cataracts. Have participated in another research study involving an investigational medicinal product in the past 12 weeks or received a gene/cell-based therapy at any time previously (including but not limited to Intelligent Implant System implantation, ciliary neurotrophic factor therapy, nerve growth factor therapy). NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 7 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subgroup 1<br>Participant's eye with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) ≥74 letters (Equivalent to: Snellen 6/9 or 20/32; decimal 0.63; Logarithm of the minimum angle of resolution [LogMAR] 0.2) will be enrolled. | Other: Other: Assessments<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB112;|
| Subgroup 2<br>Participant's eye with ETDRS BCVA 34-73 letters, inclusive (Equivalent to: Snellen 6/12 - 6/60 or 20/40 - 20/200; decimal 0.5 - 0.1; LogMAR 0.3-1.0) will be enrolled. | Other: Other: Assessments<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB112;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) | BCVA will be assessed for both eyes using the ETDRS visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant. | Up to Month 24 | 
| Change from Baseline in Retinal Sensitivity Assessed with Microperimetry | Macular analyser integrity assessment (MAIA) microperimetry will be conducted for both eyes to assess changes in retinal sensitivity within the macula. | Up to Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Contrast Sensitivity | Change from baseline in contrast sensitivity in the study eye is measured using a Pelli Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement. | Up to Month 24 | 
| Change from Baseline in Low Luminance Visual Acuity (LLVA) | LLVA is measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the participant read the normally illuminated ETDRS chart. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. LLVA is to be reported as number of letters read correctly by the participant. | Up to Month 24 | 
| Change from Baseline in 25-item Visual Function Questionnaire (VFQ-25) Score | VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. | Up to Month 24 | 
| Change from Baseline in Retinitis Pigmentosa (RP)-Specific Patient-Reported Outcome (PRO) Questionnaire |  | Up to Month 24 | 
| Change from Baseline in EuroQol-5 Dimension 5-level (EQ-5D-5L) | The widely validated EQ-5D includes 2 components, the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the subject is instructed to indicate whether he or she has no problems (level 1), slight problems (level 2), moderate problems (level 3), severe problems (level 4), or extreme problems/inability (level 5) on that day. For the EQ VAS, the participant is instructed to mark an x on a vertical scale at the point that best describes his or her own health on that day, where 0 represents the worst health he or she can imagine and 100 the best health he or she can imagine. | Up to Month 24 | 
| Change from Baseline in Health Utilities Index Mark 3 (HUI3) | The HUI3 is a generic 8-item survey, which provides descriptive evidence on multiple dimensions of health status, a score for each dimension of health, and a health-related quality of life score for overall health. Health dimensions include vision, hearing, speech, ambulation/mobility, pain, dexterity, emotion and cognition. Each dimension has five or six response options. Scores on individual items are combined to given a combined health state which can then be converted to health utilities. HUI3 score ranges from 0.36 (worst) to 1 (best). | Up to Month 24 | 
| Change from Baseline in Visual Field Readings | The progression of defects in visual fields will be assessed in both eyes using perimetry equipment. | Up to Month 24 | 
| Change from Baseline in Microperimetry Readings | MAIA microperimetry will be conducted for both eyes to assess changes other than retinal sensitivity. | Up to Month 24 | 
| Change from Baseline in Multi-Luminance Mobility Test (MLMT) Readings | The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. | Up to Month 24 | 
| Change from Baseline in Spectral Domain Optical Coherence Tomography (SD-OCT) | SD-OCT measurements will be performed after dilation of the participant's pupil. | Up Month 24 | 
| Change from Baseline in Fundus Autofluorescence (FAF) | Fundus Autofluorescence will be performed after dilation of the participant's pupil to assess changes in the area of viable retinal tissue. | Up to Month 24 | 
| Change from Baseline in Fundus Photography | Seven-field colour fundus photography will be used for both eyes. Fundus photography will be performed by certified technicians following pupil dilation. Stereo photos should be performed for fields 1, 2 and 3. | Up to Month 24 | 
| Change from Baseline in Adaptive-Optics Scanning Laser Ophthalmoscopy (AO-SLO) | Measurements will be performed after dilation of the participant's pupil. | Up to Month 24 | 
| Change from Baseline in Intraocular Pressure as Assessed by Goldmann Applanation Tonometry | Tonometry is used to measure eye pressure. After numbing the eye with eye drop anesthesia, the Goldmann tonometer presses against the eye. The force with which the eye pushes back is used to estimate the pressure inside the eye. | Up to Month 24 | 
| Change from Baseline in Morphology of Eye as Assessed by Slit-lamp Examination | The slit lamp exam usually forms part of a comprehensive eye exam. The participant will sit in a chair facing the slit lamp with their chin and forehead resting on a support. The doctor can use this instrument to observe the eyes in detail and determine whether or not there are any abnormalities. | Up to Month 24 | 
| Change from Baseline in Morphology of Eye as Assessed by Dilated Ophthalmoscopy | Dilated ophthalmoscopy is performed by dilating the participant's eye to see inside the fundus of the eye and other structures using an ophthalmoscope. | Up to Month 24 | 
| Change from Baseline in Morphology of Eye as Assessed by Lens Opacities Classification System (LOCS) III Lens Grading | LOCS III is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. | Up to Month 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RP GTPase regulator (RPGR), Degenerative retinal disease, XLRP, Natural history, Rare disease