Trial Outcomes & Findings for A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 (NCT NCT03116113)

Participants were enrolled at investigational sites in the United Kingdom (UK) and the United States (US) from 08 March 2017 to 18 November 2020.

A total of 50 participants with X-Linked Retinitis Pigmentosa (XLRP) were enrolled in the study (18 participants in Part 1 and 32 participants in Part 2). Of these, 47 participants completed the study (18 participants in Part 1 and 29 in Part 2).

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

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.