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.

NCT04855045 | Unknown Phase 2 DMC

• 1 other identifier: PQ-110-005
• Study Type: interventional
• Target: 15
• Locations: 7 countries
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of ocular adverse events (AEs)

  Incidence and severity of ocular adverse events (AEs)

  24 months

• Incidence and severity of non-ocular adverse events (AEs)

  Incidence and severity of non-ocular adverse events (AEs)

  24 months

Secondary Outcomes (2)

• 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

Study Arms (4)

Group 1 - open label

EXPERIMENTAL

Drug: sepofarsen

Group 2 - open label

EXPERIMENTAL

Drug: sepofarsen

Group 3: open label

EXPERIMENTAL

Drug: sepofarsen

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

EXPERIMENTAL

Drug: sepofarsen

Interventions

sepofarsen DRUG

RNA antisense oligonucleotide for intravitreal injection

Also known as: QR-110

Group 1 - open label; Group 2 - open label; Group 3: open label; Group 4: double-masked, randomized to one of 2 dose cohorts

Eligibility Criteria

• Age: 0 Years - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ProQR Therapeutics: lead

Study Sites (9)

Universitair Ziekenhuis Gent (UZ)

Ghent, 9000, Belgium

RECRUITING

INRET Clinica e Centro de Pesquisa / Santa Casa BH

Belo Horizonte, Brazil

RECRUITING

Federal University of Sao Paulo - Hospital Sao Paulo

São Paulo, Brazil

RECRUITING

University of Alberta

Edmonton, Alberta, Canada

NOT YET RECRUITING

Justus-Liebig Universität - Department of Ophthalmology

Giessen, 35392, Germany

RECRUITING

University of Tübingen - Institute for Ophthalmic Research

Tübingen, 72076, Germany

NOT YET RECRUITING

Eye Clinic University of Campania Liugi Vanvitelli

Naples, Italy

NOT YET RECRUITING

Amsterdam University Medica Center - Locatie AMC

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Moorfields Eye Hospital - NHS Foundation Trust

London, EC1V 2PD, United Kingdom

NOT YET RECRUITING

Related Links

• Sponsor website

MeSH Terms

Conditions

Leber Congenital Amaurosis 10; Blindness; Leber Congenital Amaurosis; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Eye Abnormalities; Retinal Diseases; Retinal Degeneration; Retinal Dystrophies; Meckel Syndrome, Type 4

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Eye Diseases, Hereditary; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• ProQR Medical Monitor

  ProQR Therapeutics

  STUDY DIRECTOR

Central Study Contacts

ProQR Clinical Trials Manager

CONTACT

+31881667000; info@proqr.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 22, 2021
• Study Start: March 23, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); BE (1); BR (2); NL (1); DE (2); GB (1); CA (1)