A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
- Conditions
- Neurologic ManifestationsBlindnessLeber Congenital AmaurosisEye DiseasesEye Disorders CongenitalVision DisordersLeber Congenital Amaurosis 10Sensation DisordersRetinal DiseaseEye Diseases, Hereditary
- Interventions
- Other: Sham
- Registration Number
- NCT03913143
- Lead Sponsor
- ProQR Therapeutics
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3: Sham Sham Sham procedure (no experimental drug administered), Day 1, month 3 and every six months there after. After 12 months cross over to active study drug may be initiated Group 1: Dose 1 sepofarsen (QR-110) sepofarsen Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated Group 2: Dose 2 sepofarsen (QR-110) sepofarsen Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated
- Primary Outcome Measures
Name Time Method Change in BCVA 12 months Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
- Secondary Outcome Measures
Name Time Method Change in FST light sensitivity 12 and 24 months Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)
Change from baseline in BCVA ≤ -0.3 LogMAR 12 and 24 months Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline
Change in oculomotor instability (OCI) 12 and 24 months Change in oculomotor instability from baseline
Change in LLVA 12 and 24 months Change from baseline in low luminance visual acuity (LLVA)
Change in FAF 12 and 24 months Change from baseline as determined by fundus autofluorescence (FAF) imaging
Change in mobility course score 12 and 24 months Change from baseline in mobility course score
Change in BCVA based on FrACT 12 and 24 months Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)
Ocular and non-ocular AEs 12 and 24 months Frequency and severity of ocular and non-ocular AEs
Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR 12 and 24 months Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.
Change in patient reported visual function via VFQ-25 (adults) 12 and 24 months Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline
Systemic exposure to QR-110 12 and 24 months Systemic exposure to QR-110
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT 12 and 24 months Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT
Changes in microperimetry 12 and 24 months Change from baseline as determined by microperimetry
Change in patient reported visual function via CVAQC (pediatrics) 12 and 24 months Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline
Change in the Patient Global Impressions of Severity (PGI-S) 12 and 24 months Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
Change in the Patient Global Impressions of Change (PGI-C) 12 and 24 months Change in the PRO Patient Global Impressions of Change (PGI-C)
Trial Locations
- Locations (14)
University of Iowa
🇺🇸Iowa City, Iowa, United States
Universitair Ziekenhuis Gent (UZ)
🇧🇪Ghent, Belgium
Moorfields Eye Hospital - NHS Foundation Trust
🇬🇧London, United Kingdom
McGill University Health Centre - Centre for Innovative Medicine
🇨🇦Montréal, Quebec, Canada
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
🇧🇷São Paulo, SP, Brazil
Hospital Civil de Strasbourg
🇫🇷Strasbourg, France
Justus-Liebig Universität - Department of Ophthalmology
🇩🇪Gießen, Germany
University of Tuebingen - Inst. for Ophthalmic Research
🇩🇪Tuebingen, Germany
Eye Clinic University of Campania Luigi Vanvitelli
🇮🇹Naples, Italy
Amsterdam University Medica Center - Locatie AMC
🇳🇱Amsterdam, Netherlands
Het Oogziekenhuis Rotterdam
🇳🇱Rotterdam, Netherlands
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
The Hospital for Sick Children - SickKids
🇨🇦Toronto, Ontario, Canada
Centre de maladies rares CHNO des Quinze Vingt
🇫🇷Paris, France