Clinical trial NCT04855045: 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.
Official title: An Open-Label, Dose Escalation and Double-Masked, Randomized, Controlled Study to Evaluate the Safety and Tolerability of Sepofarsen in Pediatric Subjects <8 Years of Age With Leber Congenital Amaurosis Type 10 (LCA10) Due to the c.2991 +1655A>G (p.Cys998X) Mutation.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
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
Keywords: LCA10
CEP290
p.Cys998X
c.2991+1655A>G
Leber Congenital Amaurosis
Antisense oligonucleotide
RNA therapy
QR-110
sepofarsen
pediatric
children
Lead sponsor: ProQR Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-04-22
Enrollment: 15
Sex: ALL
Minimum age (years): 0
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence and severity of ocular adverse events (AEs)
timeFrame: 24 months
measure: Incidence and severity of non-ocular adverse events (AEs)
timeFrame: 24 months
Secondary outcomes:
measure: Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
timeFrame: 12 months
measure: Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)
timeFrame: 12 months
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent (UZ)
city: Belo Horizonte
country: Brazil
facility: INRET Clinica e Centro de Pesquisa / Santa Casa BH
city: São Paulo
country: Brazil
facility: Federal University of Sao Paulo - Hospital Sao Paulo
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Gießen
country: Germany
facility: Justus-Liebig Universität - Department of Ophthalmology
city: Tübingen
country: Germany
facility: University of Tübingen - Institute for Ophthalmic Research
city: Naples
country: Italy
facility: Eye Clinic University of Campania Liugi Vanvitelli
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medica Center - Locatie AMC
city: London
country: United Kingdom
facility: Moorfields Eye Hospital - NHS Foundation Trust
Study officials:
affiliation: ProQR Therapeutics
name: ProQR Medical Monitor
role: STUDY_DIRECTOR
References: