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A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111 (GEMINI)

Primary Purpose

Choroideremia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BIIB111
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Choroideremia focused on measuring NightstaRx, NSR-REP1, CHM, Gene Therapy, AAV, REP1, Timrepigene Emparvovec

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Key Inclusion Criteria:

  1. Are willing and able to give informed consent for participation in the study to have both eyes treated.
  2. Have documentation of a genetically-confirmed diagnosis of CHM.
  3. Have active disease clinically visible within the macular region of both eyes.

  4. Have a BCVA of ≥34 ETDRS letters (20/200 or better Snellen acuity) in both eyes, or in the untreated eye, if the other eye was previously treated with BIIB111*

    *If previously treated with BIIB111 in an antecedent study, participants may be eligible for participation following Sponsor approval.

  5. For participants who received treatment with BIIB111 in an antecedent study, have biological samples available to complete an adequate immunology profile.

Key Exclusion Criteria:

  1. Have a history of amblyopia or inflammatory disorder in either eye.
  2. Are unwilling to use barrier contraception methods or abstain from sexual intercourse for a period of 3 months following treatment with BIIB111 in either eye.
  3. Have had previous intraocular surgery performed within 3 months of the Screening Visit in either eye.

  4. Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study or the participant's ability to participate in the study. This includes but is not limited to a potential participants:

    • with a contraindication to oral corticosteroid (e.g., prednisolone/prednisone)
    • with clinically significant cataract in either eye
    • who, in the clinical opinion of the Investigator, is not an appropriate candidate for sub-retinal surgery.
  5. Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously, except if treated within an antecedent study with BIIB111.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BIIB111

Arm Description

Participants will receive a single dose of sub-retinal injection of BIIB111 in each eye at Day 0 separated by an interval of <6 months, 6-12 months, or >12 months.

Outcomes

Primary Outcome Measures

Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12
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. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. 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.
Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12
IOP, the fluid pressure inside the eye was measured and reported in millimeters mercury (mmHg).
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination
Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment.
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy
Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve.
Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading
The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Opacification severity is graded on a decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for the Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. For each opacification type the higher grading scores indicate greater severity.
Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12
SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Total Macular Volume at Month 12
SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Central Horizontal Ellipsoid Width at Month 12
SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Square Root of Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Choroidal Thickness at Foveal Center at Month 12
SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil.
Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12
Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy.
AF: Mean Square Root of Total Area of Preserved AF at Month 12
Fundus AF was used to assess the square root of 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.
AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Fundus AF was used to assess the distance from foveal center to nearest border of preserved AF.
Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity
Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity
Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity
Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity
Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity
Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe.
Microperimetry: Retinal Mean Sensitivity at Month 12
Microperimetry was conducted to assess retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity.
Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 63%.
Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 95%.
Microperimetry: Fixation Losses (in Percentage) at Month 12
Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses.
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery.
Number of Participants With Vector Shedding Post-treatment at Month 3
Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported.
Number of Participants With Anti-drug Antibodies Post-treatment at Month 12
Participants with antibodies to the REP-1 transgenic product are reported.
Vital Signs: Change From Baseline in Blood Pressure at Month 12
Change from baseline in Systolic and diastolic blood pressures (BP) (millimeters of mercury [mmHg]) were reported.
Vital Signs: Change From Baseline in Pulse Rate at Month 12
Change from baseline in pulse rate (beats per minute) were reported.

Secondary Outcome Measures

Change From Baseline in BCVA as Measured by the ETDRS Chart
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 is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study 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.
AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
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 autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.
AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
Fundus AF was used to assess change in square root of 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. Here negative values indicate decline in total area of preserved autofluoroscence.
AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence.
SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
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: Change From Baseline in Total Macular Volume at Month 12
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: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
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: Change From Baseline in Central Ellipsoid Area at Month 12
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: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in square root of central ellipsoid area.
SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
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: Change From Baseline in Retinal Mean Sensitivity at Month 12
Microperimetry was conducted to assess change in retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity. A negative change from baseline indicates decline in retinal sensitivity.
Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
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: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
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%.
Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
Microperimetry was conducted to assess change in fixation losses (in percentage) which samples the optic nerve blind spot for positive responses. A negative change from baseline indicates decline in fixation losses.

Full Information

First Posted
March 7, 2018
Last Updated
August 21, 2023
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT03507686
Brief Title
A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111
Acronym
GEMINI
Official Title
An Open-Label Safety Study of Retinal Gene Therapy for Choroideremia With Bilateral, Sequential Administration of Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 29, 2017 (Actual)
Primary Completion Date
June 29, 2022 (Actual)
Study Completion Date
June 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of BIIB111 in adult male participants with Choroideremia (CHM).
Detailed Description
This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroideremia
Keywords
NightstaRx, NSR-REP1, CHM, Gene Therapy, AAV, REP1, Timrepigene Emparvovec

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BIIB111
Arm Type
Experimental
Arm Description
Participants will receive a single dose of sub-retinal injection of BIIB111 in each eye at Day 0 separated by an interval of <6 months, 6-12 months, or >12 months.
Intervention Type
Drug
Intervention Name(s)
BIIB111
Other Intervention Name(s)
Gene Therapy, AAV2-REP1
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12
Description
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. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. 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.
Time Frame
Month 12
Title
Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12
Description
IOP, the fluid pressure inside the eye was measured and reported in millimeters mercury (mmHg).
Time Frame
Month 12
Title
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination
Description
Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment.
Time Frame
Baseline, Month 12
Title
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy
Description
Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve.
Time Frame
Baseline, Month 12
Title
Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading
Description
The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Opacification severity is graded on a decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for the Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. For each opacification type the higher grading scores indicate greater severity.
Time Frame
Month 12
Title
Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12
Description
SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
SD-OCT: Total Macular Volume at Month 12
Description
SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
SD-OCT: Central Horizontal Ellipsoid Width at Month 12
Description
SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
SD-OCT: Central Ellipsoid Area at Month 12
Description
SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
SD-OCT: Square Root of Central Ellipsoid Area at Month 12
Description
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
SD-OCT: Choroidal Thickness at Foveal Center at Month 12
Description
SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil.
Time Frame
Month 12
Title
Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12
Description
Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy.
Time Frame
Month 12
Title
AF: Mean Square Root of Total Area of Preserved AF at Month 12
Description
Fundus AF was used to assess the square root of 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.
Time Frame
Month 12
Title
AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Description
Fundus AF was used to assess the distance from foveal center to nearest border of preserved AF.
Time Frame
Month 12
Title
Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity
Description
Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe.
Time Frame
Month 12
Title
Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity
Description
Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe.
Time Frame
Month 12
Title
Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity
Description
Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe.
Time Frame
Month 12
Title
Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity
Description
Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe.
Time Frame
Month 12
Title
Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity
Description
Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe.
Time Frame
Month 12
Title
Microperimetry: Retinal Mean Sensitivity at Month 12
Description
Microperimetry was conducted to assess retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity.
Time Frame
Month 12
Title
Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12
Description
Microperimetry was conducted to assess bivariate contour ellipse area 63%.
Time Frame
Month 12
Title
Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12
Description
Microperimetry was conducted to assess bivariate contour ellipse area 95%.
Time Frame
Month 12
Title
Microperimetry: Fixation Losses (in Percentage) at Month 12
Description
Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses.
Time Frame
Month 12
Title
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Description
An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery.
Time Frame
Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
Title
Number of Participants With Vector Shedding Post-treatment at Month 3
Description
Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported.
Time Frame
Baseline, at Month 3
Title
Number of Participants With Anti-drug Antibodies Post-treatment at Month 12
Description
Participants with antibodies to the REP-1 transgenic product are reported.
Time Frame
Month 12
Title
Vital Signs: Change From Baseline in Blood Pressure at Month 12
Description
Change from baseline in Systolic and diastolic blood pressures (BP) (millimeters of mercury [mmHg]) were reported.
Time Frame
Baseline, Month 12
Title
Vital Signs: Change From Baseline in Pulse Rate at Month 12
Description
Change from baseline in pulse rate (beats per minute) were reported.
Time Frame
Baseline, Month 12
Secondary Outcome Measure Information:
Title
Change From Baseline in BCVA as Measured by the ETDRS Chart
Description
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 is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study 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.
Time Frame
Baseline, Month 12
Title
AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
Description
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 autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.
Time Frame
Baseline, Month 12
Title
AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
Description
Fundus AF was used to assess change in square root of 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. Here negative values indicate decline in total area of preserved autofluoroscence.
Time Frame
Baseline, Month 12
Title
AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Description
Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in Total Macular Volume at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
Description
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in square root of central ellipsoid area.
Time Frame
Baseline, Month 12
Title
SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12
Description
Microperimetry was conducted to assess change in retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity. A negative change from baseline indicates decline in retinal sensitivity.
Time Frame
Baseline, Month 12
Title
Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
Description
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%.
Time Frame
Baseline, Month 12
Title
Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
Description
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%.
Time Frame
Baseline, Month 12
Title
Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
Description
Microperimetry was conducted to assess change in fixation losses (in percentage) which samples the optic nerve blind spot for positive responses. A negative change from baseline indicates decline in fixation losses.
Time Frame
Baseline, Month 12

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Are willing and able to give informed consent for participation in the study to have both eyes treated. Have documentation of a genetically-confirmed diagnosis of CHM. Have active disease clinically visible within the macular region of both eyes. Have a BCVA of ≥34 ETDRS letters (20/200 or better Snellen acuity) in both eyes, or in the untreated eye, if the other eye was previously treated with BIIB111* *If previously treated with BIIB111 in an antecedent study, participants may be eligible for participation following Sponsor approval. For participants who received treatment with BIIB111 in an antecedent study, have biological samples available to complete an adequate immunology profile. Key Exclusion Criteria: Have a history of amblyopia or inflammatory disorder in either eye. Are unwilling to use barrier contraception methods or abstain from sexual intercourse for a period of 3 months following treatment with BIIB111 in either eye. Have had previous intraocular surgery performed within 3 months of the Screening Visit in either eye. Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study or the participant's ability to participate in the study. This includes but is not limited to a potential participants: with a contraindication to oral corticosteroid (e.g., prednisolone/prednisone) with clinically significant cataract in either eye who, in the clinical opinion of the Investigator, is not an appropriate candidate for sub-retinal surgery. Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously, except if treated within an antecedent study with BIIB111. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Research Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30194931
Citation
Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
Results Reference
derived

Learn more about this trial

A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111

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