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)

• ClinicalTrials.gov Identifier: NCT03584165
• Recruitment Status: Enrolling by invitation
• First Posted: July 12, 2018
• Last Update Posted: May 8, 2023
• Sponsor: NightstaRx Ltd, a Biogen Company
• Information provided by (Responsible Party): Biogen ( NightstaRx Ltd, a Biogen Company )

Tracking Information

• First Submitted Date: June 29, 2018
• First Posted Date: July 12, 2018
• Last Update Posted Date: May 8, 2023
• Actual Study Start Date: June 4, 2018
• Estimated Primary Completion Date: June 4, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2023)

• Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 5 years ]
• Ophthalmic Examination Assessment: Intraocular Pressure (IOP) [ Time Frame: Up to 5 years ]
• Ophthalmic Examination Assessment: Abnormal Slit Lamp Examination [ Time Frame: Up to 5 years ]
• Ophthalmic Examination Assessment: Lens Opacity Grading [ Time Frame: Up to 5 years ]
• Ophthalmic Examination Assessment: Anterior Chamber and Vitreous Inflammation [ Time Frame: Up to 5 years ]
• Ophthalmic Examination Assessment: Indirect Ophthalmoscopy [ Time Frame: Up to 5 years ]

Original Primary Outcome Measures (submitted: June 29, 2018)

Safety Outcome Measures [ Time Frame: up to 5 years ]

Incidence of Adverse Events (AEs) and serious adverse events (SAEs) throughout the study period and at each study visit.

Current Secondary Outcome Measures (submitted: May 5, 2023)

• Change from Baseline in Best-Corrected Visual Acuity (BCVA) [ Time Frame: 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) Participants [ Time Frame: 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 an Increase from Baseline in BCVA of ≥10 ETDRS Letters in CHM Participants [ Time Frame: 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 an Increase from Baseline in BCVA of ≥15 ETDRS Letters in CHM Participants [ Time Frame: 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.
• Assessment of Fundus Autofluorescence (AF) at Each Visit [ Time Frame: Up 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).
• Assessment of Fundus Photography at Each Visit [ Time Frame: Up 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 Visit [ Time Frame: Up 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).
• Assessment of Microperimetry at Each Visit [ Time Frame: Up 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) [ Time Frame: 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.
• Change from Baseline in Visual Field [ Time Frame: Up 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 ≥10 ETDRS Letters in BIIB112-treated Participants [ Time Frame: 18 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 Luminance Visual Acuity (LLVA) of ≥15 ETDRS Letters in BIIB112-treated Participants [ Time Frame: 18 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.

Original Secondary Outcome Measures (submitted: June 29, 2018)

• Best Corrected Visual Acuity [ Time Frame: up to 5 years ]
  EDTRS Visual Acuity Chart
• Fundus Autofluorescence (AF) [ Time Frame: up to 5 years ]
  Change in AF (mm2)
• Optical Coherence Tomography [ Time Frame: up to 5 years ]
  Ellipsoid Zone
• Microperimetry [ Time Frame: up to 5 years ]
  Change in Sensitivity (dB)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa
• Official Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Other

Condition

• Choroideremia
• X-Linked Retinitis Pigmentosa

Intervention

• Genetic: BIIB111
  Administered as specified in the treatment arm.
  Other Names:

  • AAV2-REP1
  • rAAV2-REP1
• Genetic: BIIB112
  Administered as specified in the treatment arm.
  Other Name: AAV8-RPGR

Study Arms

• 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.
  Intervention: Genetic: BIIB111
• 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.
  Intervention: Genetic: BIIB112
• 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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: May 5, 2023): 330
• Original Estimated Enrollment (submitted: June 29, 2018): 100
• Estimated Study Completion Date: June 4, 2026
• Estimated Primary Completion Date: June 4, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Canada, Denmark, Finland, France, Germany, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT03584165
• Other Study ID Numbers: 273CH201; 2017-003104-42 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Biogen ( NightstaRx Ltd, a Biogen Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: NightstaRx Ltd, a Biogen Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: May 2023