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.

Eye Diseases Clinical Trial

— BRIGHTEN  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04855045
• Other study ID #: PQ-110-005
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 23, 2021
• Est. completion date: December 2023

Study information

• Verified date: March 2022
• Source: ProQR Therapeutics
• Contact: ProQR Clinical Trials Manager
• Phone: +31881667000
• Email: info[@]proqr.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• sepofarsen
RNA antisense oligonucleotide for intravitreal injection

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent (UZ)	Ghent
Brazil	INRET Clinica e Centro de Pesquisa / Santa Casa BH	Belo Horizonte
Brazil	Federal University of Sao Paulo - Hospital Sao Paulo	São Paulo
Canada	University of Alberta	Edmonton	Alberta
Germany	Justus-Liebig Universität - Department of Ophthalmology	Gießen
Germany	University of Tübingen - Institute for Ophthalmic Research	Tübingen
Italy	Eye Clinic University of Campania Liugi Vanvitelli	Naples
Netherlands	Amsterdam University Medica Center - Locatie AMC	Amsterdam
United Kingdom	Moorfields Eye Hospital - NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
ProQR Therapeutics

Countries where clinical trial is conducted

Belgium,  Brazil,  Canada,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of ocular adverse events (AEs)	Incidence and severity of ocular adverse events (AEs)	24 months
Primary	Incidence and severity of non-ocular adverse events (AEs)	Incidence and severity of non-ocular adverse events (AEs)	24 months
Secondary	Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)	Mean change in BCVA relative to baseline after 12 months of treatment	12 months
Secondary	Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)	Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment	12 months

External Links

•   Sponsor website