biogen/studies/attachments/NCT03496012-Synopsis.pdf

NCT03496012-Synopsis

biogen/studies/attachments/NCT03496012-LLS.pdf

NCT03496012-LLS

biogen/studies/attachments/NCT03496012-LLS_2.pdf

NCT03496012-LLS (2)

biogen/studies/attachments/NCT03496012-LLS_3.pdf

NCT03496012-LLS (3)

biogen/studies/attachments/NCT03496012-LLS_4.pdf

NCT03496012-LLS (4)

biogen/studies/attachments/NCT03496012-LLS_6.pdf

NCT03496012-LLS (6)

biogen/studies/attachments/NCT03496012-LLS_7.pdf

NCT03496012-LLS (7)

biogen/studies/attachments/NCT03496012-LLS_1.pdf

NCT03496012-LLS (1)

biogen/studies/attachments/NCT03496012-LLS_10.pdf

NCT03496012-LLS (10)

biogen/studies/attachments/NCT03496012-LLS_5.pdf

NCT03496012-LLS (5)

biogen/studies/attachments/NCT03496012-LLS_8.pdf

NCT03496012-LLS (8)

biogen/studies/attachments/NCT03496012-LLS_9.pdf

NCT03496012-LLS (9)

The objective of the study is to evaluate the efficacy and safety of a single sub-retinal
injection of BIIB111 in participants with choroideremia (CHM).

Efficacy and Safety of BIIB111 for the Treatment of Choroideremia

Choroideremia

Eye Disorders

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

BIIB111

A Randomised, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group, Phase 3 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)

BCVA was 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.
The lower the number of letters read correctly on the eye chart, the worse the vision (or
VA). Percentage of participants with a ≥15 -letter improvement from baseline in BCVA at
Month 12 was reported for both eyes.

BCVA was assessed for study eye using the ETDRS 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 was reported
as number of letters read correctly by the participant using the ETDRS Scale (ranging
from 0 to 100 letters) in the study eye. 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.

BCVA was assessed for both eyes using the ETDRS 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. The lower the
number of letters read correctly on the eye chart, the worse the vision (or VA).
Percentage of participants with a ≥10 -letter improvement from baseline in BCVA at Month
12 was reported for both eyes.

BCVA was assessed for both eyes using the ETDRS 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. The lower the
number of letters read correctly on the eye chart, the worse the vision (or VA).
Percentage of participants with no decrease or a decrease of <5 letters from baseline in
BCVA at Month 12 was reported for both eyes.

BCVA was assessed for both eyes using the ETDRS 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 was reported
as number of letters read correctly by the participant using the ETDRS Scale (ranging
from 0 to 100 letters) in both the study and fellow eyes. 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.

Fundus AF was used to assess change in total area of preserved AF. Areas of preserved AF
were identified as well-demarcated regions of relative hyper AF compared with the
background areas of surrounding atrophy. A negative change from baseline indicate decline
in total area of preserved AF.

Fundus AF was used to assess change in distance from foveal center (FC) to nearest border
of preserved AF. A negative change from baseline indicate decline in distance from FC to
nearest border of AF.

SD-OCT was used to assess change in foveal subfield thickness. The measurements were
taken after dilation of the participant's pupil. A negative change from baseline
indicates decline in foveal subfield thickness.

SD-OCT was used to assess change in total macular volume. The measurements were taken
after dilation of the participant's pupil. A negative change from baseline indicates
decline in total macular volume.

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 decline in central horizontal ellipsoid width.

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
decline in central ellipsoid area.

SD-OCT was used to assess change in choroidal thickness. The measurements were taken
after dilation of the participant's pupil. A negative change from baseline indicates
decline in choroidal thickness.

Microperimetry was conducted to assess change in mean retinal sensitivity within the
macula. Retinal mean sensitivity to light was measured in decibels (dBs) in multiple
spots across the central and peripheral retina (entire visual field). Higher numbers
(dBs) indicate higher retinal sensitivity. A negative change from baseline indicates
decline in retinal sensitivity.

Microperimetry was conducted to assess change in bivariate contour ellipse area 63%. A
negative change from baseline indicates decline in bivariate contour ellipse area 63%.

Microperimetry was conducted to assess change in bivariate contour ellipse area 95%. A
negative change from baseline indicates decline in bivariate contour ellipse area 95%.

Change in contrast sensitivity was assessed by Pelli-Robson chart which uses a single
large letter size (20/60 optotype), with contrast varying across groups of letters (6 per
line), whose contrast varies from high to low. Participants read letters, starting with
highest contrast, until they are unable to read 2 or 3 letters in a single group. Each
group had three letters of the same contrast level, so there were three trials per
contrast level. Score is assigned based on contrast of last group in which 2 or 3 letters
were correctly read. Score is a measure of participant's log contrast sensitivity ranging
from 0 (no letters read) to 2.25 (all letters read). Total CS score=[(total letters
correct-3) x 0.05]. A negative change from baseline indicates worsening in contrast
sensitivity score.

Colour vision total error scores were assessed by the Farnsworth Munsell 100 Hue Sort
Test. Farnsworth Munsell 100 Hue Test requires placing 100 colour palettes in the correct
order based upon colour hue. Scores are determined by the frequency and severity of any
displacement in the correct order. One error equates to one misplaced hue, by one step or
position. An error score of 0 indicates no errors in ordering the hues while error score
greater than 500 indicates virtually no color discrimination. A Total Error Score of 0 to
128 could be seen in a normal population.

The reading speed (words per minute) was calculated using the following formula: [number
of words in the text - number of misread words] / reading time x 60. The number of
misread words and reading time is collected. A negative change from baseline indicates
decline in reading speed.

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. A score of 0 represents the worst outcome and 100
represents the best outcome. A negative change from baseline indicates decline in VFQ-25
score.

Participants will receive a single administration of high dose BIIB111 in one eye through
sub-retinal injection after vitrectomy.

Participants will receive a single administration of low dose BIIB111 in one eye through
sub-retinal injection after vitrectomy.

Participants will receive no sham surgery or study medication.

The objective of the study is to evaluate the efficacy and safety of a single sub-retinal
      injection of BIIB111 in participants with choroideremia (CHM).

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 Early Treatment of Diabetic Retinopathy Study (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 using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

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.

VFQ-25 questionnaire measures dimensions of self-reported vision-targeted health status that are most important to persons with eye disease. Total score ranges from 0-100, where a score of 0 represents the worst outcome and 100 represents the best outcome.

Participants will receive a single administration of high dose BIIB111 in one eye through sub-retinal injection after vitrectomy.

Participants will receive a single administration of low dose BIIB111 in one eye through sub-retinal injection after vitrectomy.