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.

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.

Sponsors

Lead Sponsor: ProQR Therapeutics

Source ProQR Therapeutics
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.

Overall Status Recruiting
Start Date 2021-03-23
Completion Date 2023-12-01
Primary Completion Date 2023-12-01
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence and severity of ocular adverse events (AEs) 24 months
Incidence and severity of non-ocular adverse events (AEs) 24 months
Secondary Outcome
Measure Time Frame
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA) 12 months
Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST) 12 months
Enrollment 15
Condition
Intervention

Intervention Type: Drug

Intervention Name: sepofarsen

Description: RNA antisense oligonucleotide for intravitreal injection

Other Name: QR-110

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.

Gender:

All

Minimum Age:

N/A

Maximum Age:

7 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
ProQR Medical Monitor Study Director ProQR Therapeutics
Overall Contact

Last Name: ProQR Clinical Trials Manager

Phone: +31881667000

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Universitair Ziekenhuis Gent (UZ) | Ghent, 9000, Belgium Recruiting Bart Leroy [email protected] Bart Leroy Principal Investigator
Justus-Liebig Universität - Department of Ophthalmology | Gießen, 35392, Germany Not yet recruiting Lyubomyr Lytvynchuk +49-641-985-43803 [email protected] Lyubomyr Lytvynchuk Principal Investigator
University of Tübingen - Institute for Ophthalmic Research | Tübingen, 72076, Germany Not yet recruiting Andrea Rindtorff +49 7071 29 87747 [email protected] Katarina Stingl, MD Principal Investigator
Amsterdam University Medica Center - Locatie AMC | Amsterdam, 1105 AZ, Netherlands Recruiting Monique Wezel +31 205668618 [email protected] Camiel Boon Principal Investigator
Moorfields Eye Hospital - NHS Foundation Trust | London, EC1V 2PD, United Kingdom Not yet recruiting Flora Kakanou +44 0207 253 3411 2109 [email protected] Michel Michaelides Principal Investigator
Location Countries

Belgium

Germany

Netherlands

United Kingdom

Verification Date

2021-04-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Group 1 - open label

Type: Experimental

Label: Group 2 - open label

Type: Experimental

Label: Group 3: open label

Type: Experimental

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

Type: Experimental

Acronym BRIGHTEN
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Sequential Assignment

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

Masking: Triple (Participant, Care Provider, Investigator)

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