biogen/studies/attachments/NCT04926129-LLS_Dutch_Netherlands.pdf

NCT04926129-LLS Dutch (Netherlands)

biogen/studies/attachments/NCT04926129-LLS.pdf

NCT04926129-LLS

biogen/studies/attachments/NCT04926129-LLS_Finnish_Finland.pdf

NCT04926129-LLS Finnish (Finland)

biogen/studies/attachments/NCT04926129-LLS_French_Canada.pdf

NCT04926129-LLS French (Canada)

biogen/studies/attachments/NCT04926129-LLS_French_France.pdf

NCT04926129-LLS French (France)

biogen/studies/attachments/NCT04926129-LLS_German_Germany.pdf

NCT04926129-LLS German (Germany)

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

Natural History of the Progression of X-Linked Retinitis Pigmentosa

X-Linked Retinitis Pigmentosa

Eye Disorders

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

Other: Assessments

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.

Macular analyser integrity assessment (MAIA) microperimetry will be conducted for both
eyes to assess changes in retinal sensitivity within the macula.

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.

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.

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.

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.

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).

The progression of defects in visual fields will be assessed in both eyes using perimetry
equipment.

MAIA microperimetry will be conducted for both eyes to assess changes other than retinal
sensitivity.

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.

SD-OCT measurements will be performed after dilation of the participant's pupil.

Fundus Autofluorescence will be performed after dilation of the participant's pupil to
assess changes in the area of viable retinal tissue.

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.

Measurements will be performed after dilation of the participant's pupil.

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.

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.

Dilated ophthalmoscopy is performed by dilating the participant's eye to see inside the
fundus of the eye and other structures using an ophthalmoscope.

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.

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.

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.

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

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

Research Site

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.

Macular analyser integrity assessment (MAIA) microperimetry will be conducted for both eyes to assess changes in retinal sensitivity within the macula.

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.

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.

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.

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.

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).

The progression of defects in visual fields will be assessed in both eyes using perimetry equipment.

MAIA microperimetry will be conducted for both eyes to assess changes other than retinal sensitivity.

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.

Fundus Autofluorescence will be performed after dilation of the participant's pupil to assess changes in the area of viable retinal tissue.

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.

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.

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.

Dilated ophthalmoscopy is performed by dilating the participant's eye to see inside the fundus of the eye and other structures using an ophthalmoscope.

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.

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.

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.