Blindness, Eye Diseases, Eye Disorders Congenital, Leber Congenital Amaurosis, Leber Congenital Amaurosis 10, Neurologic Manifestations, Retinal Degeneration, Retinal Disease, Retinal Dystrophies, Sensation Disorders, Vision Disorders
Conditions
Keywords
LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen, pediatric, children
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.
Interventions
DRUGsepofarsen
RNA antisense oligonucleotide for intravitreal injection
Sponsors
ProQR Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
Eligibility
Sex/Gender
ALL
Age
0 Years to 7 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
Belgium, Brazil, Canada, Germany, Italy, Netherlands, United Kingdom
Contacts
Primary ContactProQR Clinical Trials Manager
Outcome results
None listed