Efficacy and Safety of BIIB111 for the Treatment of Choroideremia

Overview

The objective of the study is to evaluate the efficacy and safety of a single sub-retinal injection of BIIB111 in participants with choroideremia (CHM).

Full Title of Study: “A Randomised, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group, Phase 3 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 1, 2020

Detailed Description

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

Interventions

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

Arms, Groups and Cohorts

  • Experimental: BIIB111 High Dose
    • Participants will receive a single administration of high dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
  • Experimental: BIIB111 Low Dose
    • Participants will receive a single administration of low dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
  • No Intervention: Untreated Control Group
    • Participants will receive no sham surgery or study medication.

Clinical Trial Outcome Measures

Primary Measures

  • Percentage of Participants with a ≥15-Letter Improvement from Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart
    • Time Frame: Month 12
    • 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.

Secondary Measures

  • Change from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
    • Time Frame: Month 12
    • 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 a ≥10-Letter Improvement from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
    • Time Frame: Month 12
    • 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 at Month 12 Measured by the EDRS Chart
    • Time Frame: Month 12
    • 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.
  • Change from Baseline in BCVA at Months 4 and 8
    • Time Frame: Months 4 and 8
    • 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.
  • Change from Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12
    • Time Frame: Month 12
  • Change from Baseline in the Area of Preserved Ellipsoid Zone Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12
    • Time Frame: Months 12
  • Change from Baseline in Microperimetry at Month 12
    • Time Frame: Month 12
  • Change from Baseline in Contrast Sensitivity Score at Month 12
    • Time Frame: Month 12
    • Change from baseline in contrast sensitivity in the study eye is measured using a Pelli Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.
  • Change from Baseline in Colour Vision at Month 12
    • Time Frame: Month 12
  • Change from Baseline in Reading Speed Test at Month 12
    • Time Frame: Month 12
  • Change from Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) at Month 12
    • Time Frame: Month 12
    • 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.

Participating in This Clinical Trial

Key Inclusion Criteria:

  • Are willing and able to give informed consent for participation in the study. – Have a documented genetically-confirmed diagnosis of CHM. – Have active disease clinically visible within the macular region in the study eye. – Have a BCVA of 34-73 ETDRS letters (equivalent to worse than or equal to 6/12 or 20/40 Snellen acuity, but better than or equal to 6/60 or 20/200 Snellen acuity) in the study eye. Key Exclusion Criteria:

  • Have a history of amblyopia in the eligible eye. – Have had previous intraocular surgery performed in the study eye within 3 months of Visit 1. – 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. – 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. – Are unwilling to use barrier contraception methods, or abstain from sexual intercourse, for a period of 3 months, if treated with AAV2-REP1. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • NightstaRx Ltd, a Biogen Company
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Biogen

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