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Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa

Phase 3
Conditions
Choroideremia
X-Linked Retinitis Pigmentosa
Interventions
Genetic: BIIB111
Genetic: BIIB112
Registration Number
NCT03584165
Lead Sponsor
NightstaRx Ltd, a Biogen Company
Brief Summary

The objective of the study is to evaluate the long-term safety and efficacy of a sub-retinal injection of BIIB111 in participants with Choroideremia (CHM) who have been previously treated with BIIB111 and who have exited an antecedent study; these treated participants will be compared with untreated control participants who have exited the STAR (NCT03496012) study and BIIB112 in participants with X-linked retinitis pigmentosa (XLRP) who have been previously treated with BIIB112 and who have exited an antecedent study.

Detailed Description

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

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
Male
Target Recruitment
330
Inclusion Criteria

CHM Participants

a. Have participated in and exited from an interventional study that investigated the safety and efficacy of a sub-retinal injection of BIIB111 for CHM.

XLRP Participants

a. Have received a sub-retinal injection of BIIB112 for XLRP and have exited an antecedent study.

Key

Exclusion Criteria

Participants are not eligible for study participation if they meet the following exclusion criterion.

a. In the opinion of the Investigator and/or the Sponsor, it is not in the participant's best interest to participate in the study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BIIB111BIIB111Participants previously treated with sub-retinal injection of BIIB111 in antecedent studies 273CH301 (NCT03496012) and 273CH203 (NCT03507686) will be enrolled. Participants previously treated with this same sub-retinal injection (rAAV2-REP1) in antecedent studies 20150371 (NCT02553135), Pro00028599 (NCT02077361), THOR-TUE-01 (NCT02671539), CHM09/01 (NCT01461213) and REGEN2015 (NCT02407678) will also be invited for enrollment. This is a follow-up study, investigational product was administered in the previous study.
BIIB112BIIB112Participants previously treated with sub-retinal injection of BIIB112 in the antecedent study 274RP101 (NCT03116113) will be enrolled. This is a follow-up study, investigational product was administered in the previous study.
Primary Outcome Measures
NameTimeMethod
Ophthalmic Examination Assessment: Lens Opacity GradingUp to 5 years
Ophthalmic Examination Assessment: Anterior Chamber and Vitreous InflammationUp to 5 years
Percentage of Participants with Adverse Events (AEs)Up to 5 years
Ophthalmic Examination Assessment: Intraocular Pressure (IOP)Up to 5 years
Ophthalmic Examination Assessment: Abnormal Slit Lamp ExaminationUp to 5 years
Ophthalmic Examination Assessment: Indirect OphthalmoscopyUp to 5 years
Secondary Outcome Measures
NameTimeMethod
Change from Baseline in Best-Corrected Visual Acuity (BCVA)Up to 5 years

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.

Percentage of Participants with no Decrease from Baseline in BCVA or a Decrease from Baseline in BCVA of <5 ETDRS Letters in Choroideremia (CHM) ParticipantsUp to 5 years

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.

Assessment of Microperimetry at Each VisitUp to 5 years

Microperimetry will be performed on both eyes to assess changes in retinal sensitivity within the macula. It will be reported in decibels (dB).

Change from Baseline in 25-Item Visual Function Questionnaire (VFQ-25)Up to 5 years

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.

Assessment of Fundus Photography at Each VisitUp to 5 years

Fundus photography will be performed on both eyes following the dilation of the participant's pupils.

Assessment of Spectral Domain Optical Coherence Tomography (SD-OCT) at Each VisitUp to 5 years

SD-OCT will be performed on both eyes to assess the foveal changes and other potential anatomic changes. The measurements were taken after dilation of the participant's pupil and would be reported in micrometres (µm).

Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥10 ETDRS Letters in BIIB112-treated Participants18 Months to 60 Months, Post-Day 0 Visits

The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. Initially, letters are read at a distance of 4 metres from the chart. If \<20 letters are read at 4 metres, testing at 1 metre should be performed. BCVA is to be reported as number of letters read correctly by the participant.

Percentage of Participants with an Increase from Baseline in BCVA of ≥10 ETDRS Letters in CHM ParticipantsUp to 5 years

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.

Percentage of Participants with an Increase from Baseline in BCVA of ≥15 ETDRS Letters in CHM ParticipantsUp to 5 years

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.

Assessment of Fundus Autofluorescence (AF) at Each VisitUp to 5 years

Fundus Autofluoroscence will be performed on both eyes to assess the change in the area of viable retinal tissue. It will be reported in square millimetres (mm\^2).

Change from Baseline in Visual FieldUp to 5 years

The outcome measure will be assessed in BIIB112-treated participants.

Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥15 ETDRS Letters in BIIB112-treated Participants18 Months to 60 Months, Post-Day 0 Visits

The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. Initially, letters are read at a distance of 4 metres from the chart. If \<20 letters are read at 4 metres, testing at 1 metre should be performed. BCVA is to be reported as number of letters read correctly by the participant.

Trial Locations

Locations (25)

Instituto Genetica Ocular

🇧🇷

Sao Paulo, Brazil

Vitreo Retinal Associates PA - The Millennium Center

🇺🇸

Gainesville, Florida, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Cincinnati Eye Institute - Blue Ash

🇺🇸

Cincinnati, Ohio, United States

Retina Foundation of the Southwest

🇺🇸

Dallas, Texas, United States

University of Wisconsin School of Medicine

🇺🇸

Madison, Wisconsin, United States

The University of British Columbia - Eye Care Centre

🇨🇦

Vancouver, British Columbia, Canada

The Northern Alberta Clinical Trials and Research Centre

🇨🇦

Edmonton, Alberta, Canada

McGill University Health Centre

🇨🇦

Montreal, Quebec, Canada

CHU Montpellier - Saint Eloi

🇫🇷

Montpellier, France

Centre Hospitalier National d Ophtalmologie (CHNO) des Quinze-Vingts

🇫🇷

Paris, France

Universitäts-Augenklinik Bonn

🇩🇪

Bonn, Germany

Radboudumc

🇳🇱

Nijmegen, Netherlands

Universitats Klinikum Tubingen - Institute for Ophthalmic Research

🇩🇪

Tübingen, Germany

Moorfields Eye Hospital

🇬🇧

London, United Kingdom

Manchester Royal Eye Hopsital

🇬🇧

Manchester, United Kingdom

John Radcliffe Hospital

🇬🇧

Oxford, United Kingdom

Southampton General Hospital

🇬🇧

Southampton, United Kingdom

Helsinki University Central Hospital (HUCH)

🇫🇮

Helsinki, Finland

Rigshospitalet-Glostrup, Oejenafdelingen

🇩🇰

Glostrup, Denmark

UCLA - Jules Stein Eye Institute

🇺🇸

Los Angeles, California, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

MEEI Massachusets Eye and Ear Infirmary

🇺🇸

Boston, Massachusetts, United States

OHSU - Casey Eye Institute

🇺🇸

Portland, Oregon, United States

University of Miami

🇺🇸

Miami, Florida, United States

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