Phase 2 N=60 Treatment

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

Choroideremia

Bottom Line

View on ClinicalTrials.gov: NCT03507686 ↗

Enrolled (actual)

Serious AEs

17.2%

Results posted

Sep 2023

Primary outcome: Primary: Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12 — 68.0; 76.5; 82.3; 81.2 letters

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: BIIB111 (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: Biogen
Primary completion: Jun 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12	68.0; 76.5; 82.3; 81.2	—
PRIMARY Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12	13.5; 13.5; 14.9; 13.5	—
PRIMARY Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination	0; 0; 0; 0; 0; 0	—
PRIMARY Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy	0; 0; 1; 1; 0; 0	—
PRIMARY Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading	13; 38; 1; 8; 0; 4	—
PRIMARY Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12	290.7; 258.0; 283.8; 270.9	—
PRIMARY SD-OCT: Total Macular Volume at Month 12	6.770; 6.638; 6.903; 6.741	—
PRIMARY SD-OCT: Central Horizontal Ellipsoid Width at Month 12	2346.0; 1951.2; 2230.2; 1950.1	—
PRIMARY SD-OCT: Central Ellipsoid Area at Month 12	3.213; 2.971; 4.404; 3.810	—
PRIMARY SD-OCT: Square Root of Central Ellipsoid Area at Month 12	1.6980; 1.6346; 2.0331; 1.8468	—
PRIMARY SD-OCT: Choroidal Thickness at Foveal Center at Month 12	185.5; 174.2; 207.6; 190.2	—
PRIMARY Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12	7.130; 8.682; 8.157; 9.682	—
PRIMARY AF: Mean Square Root of Total Area of Preserved AF at Month 12	2.4358; 2.6149; 2.6214; 2.7550	—
PRIMARY AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12	423.133; 370.245; 539.600; 525.212	—
PRIMARY Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity	7; 26; 9; 23; 8; 21	—
PRIMARY Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity	13; 37; 12; 36; 1; 10	—
PRIMARY Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity	0; 0; 0; 0; 0; 0	—
PRIMARY Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity	0; 0; 0; 0; 0; 0	—
PRIMARY Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity	0; 1; 0; 0; 0; 0	—
PRIMARY Microperimetry: Retinal Mean Sensitivity at Month 12	4.05; 5.93; 5.41; 6.37	—
PRIMARY Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12	7.91; 2.09; 1.45; 1.92	—
PRIMARY Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12	23.69; 6.27; 4.35; 5.76	—
PRIMARY Microperimetry: Fixation Losses (in Percentage) at Month 12	9.0; 2.2; 4.0; 5.0	—
PRIMARY Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	100; 96.4	—
PRIMARY Number of Participants With Vector Shedding Post-treatment at Month 3	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Anti-drug Antibodies Post-treatment at Month 12	0; 0	—
PRIMARY Vital Signs: Change From Baseline in Blood Pressure at Month 12	122.3; 125.4; -7.2; -2.0; 78.3; 80.5	—
PRIMARY Vital Signs: Change From Baseline in Pulse Rate at Month 12	69.8; 71.5; 6.7; 0.9	—
SECONDARY Change From Baseline in BCVA as Measured by the ETDRS Chart	-8.6; -1.3; 2.2; -2.2	—
SECONDARY AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12	-1.158; -1.502; -0.772; -1.313	—
SECONDARY AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12	-0.1981; -0.2197; -0.1345; -0.1736	—
SECONDARY AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12	-160.000; -94.321; -76.000; -80.596	—
SECONDARY SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12	1.7; -2.9; -3.5; -5.7	—
SECONDARY SD-OCT: Change From Baseline in Total Macular Volume at Month 12	-0.201; -0.188; -0.093; -0.233	—
SECONDARY SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12	-156.8; -161.5; -217.5; -150.4	—
SECONDARY SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12	-0.408; -0.452; -0.466; -0.369	—
SECONDARY SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12	-0.1348; -0.1345; -0.1121; -0.0944	—
SECONDARY SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12	-12.9; -13.7; -9.8; 2.9	—
SECONDARY Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12	-0.79; -0.38; 0.15; -0.73	—
SECONDARY Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12	4.42; -0.22; -0.02; 0.63	—
SECONDARY Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12	13.23; -0.66; -0.09; 1.90	—
SECONDARY Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12	5.3; -4.5; -6.3; 2.8	—

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).

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03507686). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.