A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 (XIRIUS)

A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)

The objective of the study is to evaluate the safety, tolerability and efficacy of a single sub-retinal injection of BIIB112 in participants with X-linked retinitis pigmentosa (XLRP).

Study Overview

• Status: Completed
• Conditions: X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Biological: BIIB112

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Research Site
  • Oxford, United Kingdom
    • Research Site
  • Southampton, United Kingdom
    • Research Site
• United States
  • Florida
    • Gainesville, Florida, United States, 32607
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Part 1:

• Participants with genetically confirmed diagnosis of XLRP (with RPGR mutation).
• Participant with active disease clinically visible within the macular region in both eyes.

Part 2:

- Participant with mean total retinal sensitivity in the study eye as assessed by microperimetry ≥ 0.1 dB and ≤8 dB.

Key exclusion Criteria:

Parts 1 and 2:

• Participant with history of amblyopia in either eye.
• Participated in a gene therapy trial previously or a clinical trial with an investigational drug in the past 12 weeks or received a gene/cell-based therapy at any time previously.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BIIB112 Dose 1; Participants will receive a single Dose 1 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 1: BIIB112 Dose 2; Participants will receive a single Dose 2 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 1: BIIB112 Dose 3; Participants will receive a single Dose 3 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 1: BIIB112 Dose 4; Participants will receive a single Dose 4 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 1: BIIB112 Dose 5; Participants will receive a single Dose 5 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 1: BIIB112 Dose 6; Participants will receive a single Dose 6 of BIIB112 by sub-retinal injection on Day 0.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 2: BIIB112 High Dose; Participants will receive a single high dose of BIIB112 by sub-retinal injection.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
Experimental: Part 2: BIIB112 Low Dose; Participants will receive a single low dose of BIIB112 by sub-retinal injection.	Biological: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
No Intervention: Part 2: Untreated Group; Participants will receive no intervention to allow for a controlled comparison.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)	DLTs are defined as any of the following events considered to be related to study drug: Sustained decrease in best-corrected visual acuity (BCVA) of ≥30 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart compared to baseline (sustained is defined as lasting 48 hours or more until recovery, with recovery defined as visual acuity (VA) returning to within 10 letters of baseline VA. An exception is made for surgery-related events occurring in close temporal association {within <24 hours} of the surgery); Vitreous inflammation, vitritis (>Grade 3 using standardized Nussenblatt vitreous inflammation scale grading); Any clinically significant retinal damage observed that is not directly attributed to complications of surgery; Any clinically relevant suspected unexpected serious adverse reaction, with the exception of vision loss or vision threatening.	Up to Month 24
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as the AEs starting or worsening on or after the day of the first surgery.	Day 0 (surgery) in Part 1 of the study up to 24 months
Part 2: Percentage of Study Eyes With ≥7 Decibels (dB) Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0', or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.	Month 12
Part 2: Number of Participants With TEAEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as AEs starting on or after the day of the first surgery.	Day 0 (surgery) in Part 2 of the study up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points).	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points. Here negative values indicate a decline in retinal sensitivity.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Mean Best Corrected Visual Acuity (BCVA) Reported as Letters	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was reported as number of letters read correctly by the participants using the ETDRS Scale (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Here negative values indicate decline in BCVA.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Mean Low Luminance Visual Acuity (LLVA) Reported as Letters	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Here negative values indicate decline in LLVA.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥15 Letters Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥10 Letters Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥5 Letters Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Percentage of eyes with a change from baseline of ≥ -5 letters for BCVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Percentage of Eyes With Change From Baseline > -5 Letters for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Percentage of eyes with a change from baseline of ≥ -5 letters for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Central Ellipsoid Area	Spectral Domain Optical Coherence Tomography (SD-OCT) was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates a decline in central ellipsoid area.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Central Horizontal Ellipsoid Width	SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates a decline in central horizontal ellipsoid width.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Total Area of Preserved Autofluoroscence	Fundus Autofluoroscence was used to assess the total area of preserved autofluoroscence. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. A negative change from baseline indicates a decline in total area of preserved autofluoroscence.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Fundus Autofluoroscence- Mean Distance From Foveal Center (FC) to Nearest Border of Preserved Autofluoroscence	Fundus Autofluoroscence was used to assess the distance from FC to nearest border of preserved autofluoroscence. A negative change from baseline indicates a decline in the total area of preserved autofluoroscence.	Baseline, Months 1, 3, 6, 9, 12, 18, and 24
Part 1: Change From Baseline in Mean Volume of 30-Degree Hill of Vision	Visual field testing was performed to assess the volume of 30-degree hill vision, reported as dBs. Reliability Factor (RF)=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of 30-degree hill vision.	Baseline, Months 6, 12, and 24
Part 1: Change From Baseline in Mean Volume of Full Field Hill of Vision	Visual field testing was performed to assess the volume of full field of hill vision, reported as dBs. RF =number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of 30-degree hill vision.	Baseline, Months 6, 12, and 24
Part 1: Change From Baseline in Contrast Sensitivity (CS) Score	Change in CS was assessed by Pelli-Robson chart which uses a single large letter size (20/60 optotype), with contrast varying across groups of letters. Chart uses letters (6 per line), arranged in groups whose contrast varies from high to low. Participants read the letters, starting with the highest contrast, until they were unable to read two or three letters in a single group. Each group had three letters of the same contrast level, so there were three trials per contrast level. Participant is assigned a score based on the contrast of the last group in which two or three letters were correctly read. Score is a measure of the participant's log contrast sensitivity ranging from 0-2.25, with 0 being no letters read, and 2.25 being all letters read. Total CS score = [(total letters correct - 3) x 0.05].	Baseline, Months 3, 6, 12, and 24
Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dBs using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' is assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.	Months 1, 2, 3, 6, and 9
Part 2: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dBs using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in mean sensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points).	Months 1, 2, 3, 6, 9, and 12
Part 2: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Mean Sensitivity in center grid was defined as the mean in dB of the 16 points located in the center of the grid. Here negative values indicate a decline in retinal sensitivity.	Baseline, Months 1, 2, 3, 6, 9, and 12
Part 2: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry	MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '< 0', '0' or a positive integer. The point labelled as '< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in mean ensitivity in whole grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points of the grid as a whole (68 points). Here negative values indicate a decline in retinal sensitivity.	Baseline, Months 1, 2, 3, 6, 9, and 12
Part 2: Change From Baseline in BCVA Reported as Letters	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. BCVA was reported as number of letters read correctly by the participant, using the ETDRS Scale (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Here negative values indicate a decline in BCVA.	Baseline, Months 1, 2, 3, 6, 9, and 12
Part 2: Change From Baseline in Mean LLVA Reported as Letters	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. LLVA was reported as number of letters read correctly by the participant, using the ETDRS Scale (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Here negative values indicate a decline in LLVA.	Baseline, Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥15 Letter Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved. Percentage of eyes with a ≥10 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥10 Letter Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥5 Letter Increase From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters increase from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥15 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥15 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥10 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥10 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With a ≥5 Letters Loss From Baseline for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a ≥5 letters loss from baseline for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for BCVA	BCVA was assessed for both eyes using the ETDRS VA chart. Initially, letters were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a change from baseline of ≥ -5 letters for BCVA were reported for study and non-study eyes.	Months 1, 2, 3, 6, 9, and 12
Part 2: Percentage of Eyes With Change From Baseline >-5 Letters for LLVA	LLVA was 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 were read at a distance of 4 meters from the chart. If <20 letters were read at 4 meters, testing at 1 meter was performed. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). Percentage of eyes with a change from baseline of ≥ -5 letters for LLVA were reported for study and non-study eyes.	Months 1, 3, 6, 9, and 12
Part 2: Change From Baseline in Volume of 30-Degree Hill of Vision Assessed by Octopus 900	Visual field testing was performed to assess the volume of 30-degree hill vision, reported as dBs. RF=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in the volume of 30-degree hill vision.	Baseline, Months 3, 6, and 12
Part 2: Change From Baseline in Volume of Full Field Hill of Vision Assessed by Octopus 900	Visual field testing was performed to assess the volume of full field of hill vision, reported as dBs. RF=number of false positive responses + number of false negative responses/number of false positive presentations + number of false negative presentations*100. If there are 0 responses, then RF value=0. RFpositive=number of false positive responses/number of false positive presentations*100. If RF≤ 20% measurement is considered reliable. If 20% < RF ≤ 25% and RFpositive ≤ 10% measurement is also considered reliable. Otherwise if 20% < RF ≤ 25% and RFpositive > 10%, or RF > 25%, measurement is not reliable. Only reliable measurements were included for analysis of this outcome measure. Here negative values indicate decline in volume of full field hill vision.	Baseline, Months 3, 6, and 12

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

General Publications

• Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, Nanda A, Davies A, Wood LJ, Salvetti AP, Fischer MD, Aylward JW, Barnard AR, Jolly JK, Luo E, Lujan BJ, Ong T, Girach A, Black GCM, Gregori NZ, Davis JL, Rosa PR, Lotery AJ, Lam BL, Stanga PE, MacLaren RE. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020 Mar;26(3):354-359. doi: 10.1038/s41591-020-0763-1. Epub 2020 Feb 24.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Ophthalmology; XLRP; Retinitis Pigmentosa GTPase Regulator (RPGR); AAV8
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: 274RP101; 2016-003852-60 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

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