The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment. At study start subjects will be randomized to one of 3 treatment groups with either active study drug or sham treatment. Sepofarsen (QR-110) will be administered via intravitreal (IVT) injection into the subject's treatment eye (the subject's worse eye). Subjects in the sham-procedure group will undergo a procedure that will closely mimic the active injection. After each dosing subjects will be assessed for safety and tolerability at follow up visits. After the first eye has been treated for at least 12 months, treatment of the contralateral eye and cross-over of subjects assigned to sham procedure may be initiated in eligible eyes (in a masked manner) based on assessment of benefit/risk (including review of data from all clinical trials), and with concurrence of the Medical Monitor.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
RNA antisense oligonucleotide for intravitreal injection
Sham-Procedure (no experimental drug administered)
University of Iowa
Iowa City, Iowa, United States
Universitair Ziekenhuis Gent (UZ)
Ghent, Belgium
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, Brazil
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
São Paulo, São Paulo, Brazil
The Hospital for Sick Children - SickKids
Toronto, Ontario, Canada
McGill University Health Centre - Centre for Innovative Medicine
Montreal, Quebec, Canada
Centre de maladies rares CHNO des Quinze Vingt
Paris, France
Hospital Civil de Strasbourg
Strasbourg, France
Justus-Liebig Universität - Department of Ophthalmology
Giessen, Germany
University of Tuebingen - Inst. for Ophthalmic Research
Tübingen, Germany
...and 4 more locations
Change in BCVA
Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
Time frame: 12 months
Change from baseline in BCVA ≤ -0.3 LogMAR
Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline
Time frame: 12 and 24 months
Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR
Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.
Time frame: 12 and 24 months
Change in BCVA based on FrACT
Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)
Time frame: 12 and 24 months
Change in mobility course score
Change from baseline in mobility course score
Time frame: 12 and 24 months
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT
Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT
Time frame: 12 and 24 months
Change in oculomotor instability (OCI)
Change in oculomotor instability from baseline
Time frame: 12 and 24 months
Change in FST light sensitivity
Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)
Time frame: 12 and 24 months
Change in LLVA
Change from baseline in low luminance visual acuity (LLVA)
Time frame: 12 and 24 months
Change in patient reported visual function via VFQ-25 (adults)
Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline
Time frame: 12 and 24 months
Change in patient reported visual function via CVAQC (pediatrics)
Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline
Time frame: 12 and 24 months
Change in the Patient Global Impressions of Severity (PGI-S)
Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
Time frame: 12 and 24 months
Change in the Patient Global Impressions of Change (PGI-C)
Change in the PRO Patient Global Impressions of Change (PGI-C)
Time frame: 12 and 24 months
Change in FAF
Change from baseline as determined by fundus autofluorescence (FAF) imaging
Time frame: 12 and 24 months
Changes in microperimetry
Change from baseline as determined by microperimetry
Time frame: 12 and 24 months
Systemic exposure to QR-110
Systemic exposure to QR-110
Time frame: 12 and 24 months
Ocular and non-ocular AEs
Frequency and severity of ocular and non-ocular AEs
Time frame: 12 and 24 months
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