Study to test the safety and tolerability of different doses (amounts) of sepofarsen (an RNA therapy) in children less than 8 years that have CEP290 mediated Leber Congenital Amaurosis 10 (LCA10) due to the c.2991+1655A>G mutatio

Phase 1

• Conditions: eber Congenital Amaurosis 10 (LCA10) due to c.2991+1655A>G mutation (p.Cys998X) in the CEP290 Gene; MedDRA version: 20.0Level: PTClassification code 10070667Term: Leber's congenital amaurosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2020-000535-45-BE
• Lead Sponsor: ProQR Therapeutics IV B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-11
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Male or female child, <8 years of age at Screening
2. A clinical diagnosis of LCA and a molecular diagnosis of homozygosity
or compound heterozygosity for the c.2991+1655A>G mutation in the
CEP290 gene, based on genotyping analysis at Screening. Historic
genotyping results from a certified laboratory are acceptable with
Sponsor approval.
3. Best corrected visual acuity (BCVA) equal to or better than Light
Perception, and equal to or worse than approximate Snellen equivalent
20/50 in the treatment eye.
4. Clear ocular media and adequate pupillary dilation to permit good
quality retinal imaging, as determined by the Investigator.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Presence of additional homozygous or compound heterozygous pathogenic mutations (other than the c.2991+1655A>G mutation in the CEP290 gene) in genes associated with other recessive inherited retinal degenerative diseases or syndromes (eg, Usher syndrome) based on genetic analysis.
2.Presence of (likely) pathogenic mutations in genes associated with dominant or X-linked inherited retinal degenerative diseases or syndromes (eg. autosomal dominant retinitis pigmentosa, X-linked Retinoschisis) based on genetic analysis.
3.Presence of any significant ocular or non-ocular disease/disorder (including lab/medication abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either 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. This includes but is not limited a subject who: 1) is not an appropriate candidate for antisense oligonucleotide treatment, 2) has concurrent cystoid macular edema (CME) in the treatment eye.
4.History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in the treatment eye.
5.Presence of any active ocular infection in either eye.
6.Presence of any of the following lens opacities in the treatment eye: cortical opacity = +2, posterior subcapsular opacity = +2, or a nuclear sclerosis = +2, and which: 1) is clinically significant in the opinion of the Investigator, or 2) would adequately prevent clinical and photographic evaluation of the retina.
7.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. Subjects who received an intraocular or periocular surgery between 1 to 3 months prior Screening, may only be considered for inclusion (at the discretion of the Investigator) if there are no clinically significant complications of surgery present.
8.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). Subjects that have been treated with systemic steroids within the past 12 months or that require intermittent use of topical steroids may be considered for inclusion based on Investigator judgement, dependent on the status of the underlying disease.
9.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 including, but not limited to, systemic/intraocular steroids, amiodarone, desferrioxamine/desferoxamine, chloroquine/hydroxychloroquine sulfate (Plaquenil), tamoxifen, ethambutol, phenothiazine derivatives including chlorpromazine, fluphenazine (decanoate), levomepromazine, and thioridazine.
10.A history of glaucoma in the treatment eye or raised intraocular pressure in the treatment eye that is not controlled with medication at the time of Screening.
11.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.
12.Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified