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 Amaurosis 10; Blindness; Leber Congenital Amaurosis; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Eye Disorders Congenital; Retinal Disease; Retinal Degeneration; Retinal Dystrophies

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 (\ g mutation over 24 months of treatment.

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 (\ 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.

Eligibility criteria:
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.

Keywords: lca10 cep290 p.cys998x c.2991+1655a>g leber congenital amaurosis antisense oligonucleotide rna therapy qr-110 sepofarsen pediatric children