An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
- Conditions
- Leber Congenital AmaurosisEye Disorders CongenitalRetinal DegenerationRetinal DystrophiesBlindnessSensation DisordersEye DiseasesRetinal DiseaseLeber Congenital Amaurosis 10Vision Disorders
- Interventions
- Registration Number
- NCT04855045
- Lead Sponsor
- ProQR Therapeutics
- Brief Summary
PQ-110-005 (BRIGHTEN) is an open-label, dose escalation and double-masked, randomized, controlled study evaluating safety and tolerability of sepofarsen administered via intravitreal (IVT) injection in pediatric subjects (\<8 years of age) with LCA10 due to the c.2991+1655A\>G mutation over 24 months of treatment.
- Detailed Description
This is an open-label, dose escalation and double-masked, randomized, controlled study evaluating safety and tolerability of sepofarsen administered via intravitreal (IVT) injection in pediatric subjects (\<8 years of age) with LCA10 due to the c.2991+1655A\>G mutation. The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
In the open label part; subjects will be assigned to one of 3 planned dose groups using a staggered dose escalation design. After at least 1 patient is dosed in each group; the Data Monitoring Committee (DMC) will review at least 4 weeks of safety data post dosing; and may recommend initiation of the next dose group. The DMC may recommend initiation of the double-masked randomized part of the study after completion of the last dose group in the dose escalation part of the study.
In the double-masked, randomized, controlled part of the study; subjects will be randomized to one of 2 planned dose groups .
Subjects will receive a unilateral IVT injection of sepofarsen on Day 1. Thereafter a 6-monthly dosing schedule is planned.
After each dosing subjects will be assessed for safety and tolerability at follow up visits.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 15
- Male or female child, <8 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. A historic genotyping report from a certified laboratory are acceptable with Sponsor approval.
- BCVA equal to or better than Logarithm of the Minimum Angle of Resolution (logMAR) + 4.0 (Light Perception), and equal to or worse than logMAR + 0.4 in the treatment eye.
- Detectable outer nuclear layer (ONL) in the area of the macula.
- Presence of any significant ocular or non-ocular disease/disorder which may put the subject at risk because of participation in the trial' may influence the results of the trial, or the subject's ability to participate in the trial.
- Receipt within 1 month prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the trial.
- Current treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to cytostatics, interferons, TNF-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system).
- Current treatment or treatment within the past 3 months or planned treatment with drugs known to be toxic to the lens, retina, or the optic nerve.
- Use of any investigational drug or device within 3 months or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the trial period.
- Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Group 2 - open label sepofarsen - Group 1 - open label sepofarsen - Group 4: double-masked, randomized to one of 2 dose cohorts sepofarsen - Group 3: open label sepofarsen -
- Primary Outcome Measures
Name Time Method Incidence and severity of ocular adverse events (AEs) 24 months Incidence and severity of ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs) 24 months Incidence and severity of non-ocular adverse events (AEs)
- Secondary Outcome Measures
Name Time Method Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST) 12 months Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA) 12 months Mean change in BCVA relative to baseline after 12 months of treatment
Trial Locations
- Locations (9)
Amsterdam University Medica Center - Locatie AMC
🇳🇱Amsterdam, Netherlands
University of Tübingen - Institute for Ophthalmic Research
🇩🇪Tübingen, Germany
Eye Clinic University of Campania Liugi Vanvitelli
🇮🇹Naples, Italy
Universitair Ziekenhuis Gent (UZ)
🇧🇪Ghent, Belgium
Federal University of Sao Paulo - Hospital Sao Paulo
🇧🇷São Paulo, Brazil
Justus-Liebig Universität - Department of Ophthalmology
🇩🇪Gießen, Germany
INRET Clinica e Centro de Pesquisa / Santa Casa BH
🇧🇷Belo Horizonte, Brazil
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Moorfields Eye Hospital - NHS Foundation Trust
🇬🇧London, United Kingdom