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

A Long-term Follow-up Study to Evaluate the Safety and Efficacy of Retinal Gene Therapy in Subjects With Choroideremia Previously Treated With Adeno-Associated Viral Vector Encoding Rab Escort Protein-1 (AAV2-REP1) and in Subjects With X-Linked Retinitis Pigmentosa Previously Treated With Adeno-Associated Viral Vector Encoding RPGR (AAV8-RPGR) in an Antecedent Study

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Choroideremia; X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Genetic: BIIB111; Genetic: BIIB112

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04039
    • Instituto Genetica Ocular
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • The Northern Alberta Clinical Trials and Research Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 39N
      • The University of British Columbia - Eye Care Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3JI
      • McGill University Health Centre
• Denmark
  • Glostrup, Denmark, 2600
    • Rigshospitalet-Glostrup, Oejenafdelingen
• Finland
  • Helsinki, Finland, 00290 HUS
    • Helsinki University Central Hospital (HUCH)
• France
  • Montpellier, France, 34295
    • CHU Montpellier - Saint ELOI
  • Paris, France, 75012
    • Centre Hospitalier National d Ophtalmologie (CHNO) des Quinze-Vingts
• Germany
  • Bonn, Germany, 53127
    • Universitats-Augenklinik Bonn
  • Tübingen, Germany, 72076
    • Universitats Klinikum Tubingen - Institute for Ophthalmic Research
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboudumc
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Eye Hopsital
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095-7065
      • UCLA - Jules Stein Eye Institute
  • Florida
    • Gainesville, Florida, United States, 32607
      • Vitreo Retinal Associates PA - The Millennium Center
    • Miami, Florida, United States, 33136
      • University of Miami
  • Maryland
    • Baltimore, Maryland, United States, 21287-0005
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-3002
      • MEEI Massachusets Eye and Ear Infirmary
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242-5664
      • Cincinnati Eye Institute - Blue Ash
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU - Casey Eye Institute
  • Texas
    • Dallas, Texas, United States, 75231-5080
      • Retina Foundation of the Southwest
  • Wisconsin
    • Madison, Wisconsin, United States, 53705-3644
      • University of Wisconsin School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB111; Participants 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.	Genetic: BIIB111; Administered as specified in the treatment arm.; Other Names: AAV2-REP1; rAAV2-REP1
Experimental: BIIB112; Participants 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.	Genetic: BIIB112; Administered as specified in the treatment arm.; Other Names: AAV8-RPGR
No Intervention: Untreated; Untreated participants who served as controls in the antecedent study 273CH301 (NCT03496012), investigating treatment with BIIB111, will be enrolled. This is a follow-up study, participants will not be administered study medication nor receive a sham surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Examination	Up to 5 years
Ophthalmic Examination Assessment: Lens Opacity Grading	Up to 5 years
Ophthalmic Examination Assessment: Anterior Chamber and Vitreous Inflammation	Up to 5 years
Ophthalmic Examination Assessment: Indirect Ophthalmoscopy	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Best-Corrected Visual Acuity (BCVA)	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.	Up to 5 years
Percentage of Participants with no Decrease from Baseline in BCVA or a Decrease from Baseline in BCVA of <5 ETDRS Letters in Choroideremia (CHM) Participants	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.	Up to 5 years
Percentage of Participants with an Increase from Baseline in BCVA of ≥10 ETDRS Letters in CHM Participants	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.	Up to 5 years
Percentage of Participants with an Increase from Baseline in BCVA of ≥15 ETDRS Letters in CHM Participants	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.	Up to 5 years
Change from Baseline in 25-Item Visual Function Questionnaire (VFQ-25)	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.	Up to 5 years
Change from Baseline in Visual Field	The outcome measure will be assessed in BIIB112-treated participants.	Up to 5 years
Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥10 ETDRS Letters in BIIB112-treated Participants	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.	18 Months to 60 Months, Post-Day 0 Visits
Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥15 ETDRS Letters in BIIB112-treated Participants	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.	18 Months to 60 Months, Post-Day 0 Visits
Assessment of Fundus Autofluorescence (AF) at Each Visit	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).	Up to 5 years
Assessment of Fundus Photography at Each Visit	Fundus photography will be performed on both eyes following the dilation of the participant's pupils.	Up to 5 years
Assessment of Spectral Domain Optical Coherence Tomography (SD-OCT) at Each Visit	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).	Up to 5 years
Assessment of Microperimetry at Each Visit	Microperimetry will be performed on both eyes to assess changes in retinal sensitivity within the macula. It will be reported in decibels (dB).	Up to 5 years

Collaborators and Investigators

• Sponsor: NightstaRx Ltd, a Biogen Company

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2018
• Primary Completion (Anticipated): June 4, 2026
• Study Completion (Anticipated): June 4, 2026

Study Registration Dates

• First Submitted: June 29, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; AAV; AAV8; CHM; RPGR; NightstaRx; NSR-REP1; REP1; Biogen
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Uveal Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Choroid Diseases; Retinitis; Retinitis Pigmentosa; Choroideremia
• Other Study ID Numbers: 273CH201; 2017-003104-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No