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. (BRIGHTEN)

ProQR Therapeutics

Status and phase: Unknown; Phase 3; Phase 2

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

Treatments: Drug: sepofarsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT04855045

PQ-110-005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: Under 7 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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15 participants in 4 patient groups

Group 1 - open label

Experimental group

Treatment:

Drug: sepofarsen

Group 2 - open label

Experimental group

Treatment:

Drug: sepofarsen

Group 3: open label

Experimental group

Treatment:

Drug: sepofarsen

Group 4: double-masked, randomized to one of 2 dose cohorts

Experimental group

Treatment:

Drug: sepofarsen