Clinical trial NCT03507686: A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Choroideremia
Keywords: NightstaRx
NSR-REP1
CHM
Gene Therapy
AAV
REP1
Timrepigene Emparvovec
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2018-04-25
Enrollment: 66
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12
timeFrame: Month 12
measure: Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12
timeFrame: Month 12
measure: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination
timeFrame: Baseline, Month 12
measure: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy
timeFrame: Baseline, Month 12
measure: Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading
timeFrame: Month 12
measure: Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12
timeFrame: Month 12
measure: SD-OCT: Total Macular Volume at Month 12
timeFrame: Month 12
measure: SD-OCT: Central Horizontal Ellipsoid Width at Month 12
timeFrame: Month 12
measure: SD-OCT: Central Ellipsoid Area at Month 12
timeFrame: Month 12
measure: SD-OCT: Square Root of Central Ellipsoid Area at Month 12
timeFrame: Month 12
measure: SD-OCT: Choroidal Thickness at Foveal Center at Month 12
timeFrame: Month 12
measure: Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12
timeFrame: Month 12
measure: AF: Mean Square Root of Total Area of Preserved AF at Month 12
timeFrame: Month 12
measure: AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
timeFrame: Month 12
measure: Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity
timeFrame: Month 12
measure: Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity
timeFrame: Month 12
measure: Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity
timeFrame: Month 12
measure: Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity
timeFrame: Month 12
measure: Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity
timeFrame: Month 12
measure: Microperimetry: Retinal Mean Sensitivity at Month 12
timeFrame: Month 12
measure: Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12
timeFrame: Month 12
measure: Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12
timeFrame: Month 12
measure: Microperimetry: Fixation Losses (in Percentage) at Month 12
timeFrame: Month 12
measure: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
measure: Number of Participants With Vector Shedding Post-treatment at Month 3
timeFrame: Baseline, at Month 3
measure: Number of Participants With Anti-drug Antibodies Post-treatment at Month 12
timeFrame: Month 12
measure: Vital Signs: Change From Baseline in Blood Pressure at Month 12
timeFrame: Baseline, Month 12
measure: Vital Signs: Change From Baseline in Pulse Rate at Month 12
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Change From Baseline in BCVA as Measured by the ETDRS Chart
timeFrame: Baseline, Month 12
measure: AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
timeFrame: Baseline, Month 12
measure: AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
timeFrame: Baseline, Month 12
measure: AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in Total Macular Volume at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
timeFrame: Baseline, Month 12
measure: SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
timeFrame: Baseline, Month 12
measure: Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12
timeFrame: Baseline, Month 12
measure: Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
timeFrame: Baseline, Month 12
measure: Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
timeFrame: Baseline, Month 12
measure: Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Miami
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Paris
country: France
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
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.