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)

March 24, 2022 updated by: ProQR Therapeutics

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Anticipated)

15

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: ProQR Clinical Trials Manager
  • Phone Number: +31881667000
  • Email: info@proqr.com

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • Recruiting
        • Universitair Ziekenhuis Gent (UZ)
        • Contact:
        • Principal Investigator:
          • Bart Leroy
  • Brazil
      • Belo Horizonte, Brazil
        • Recruiting
        • INRET Clinica e Centro de Pesquisa / Santa Casa BH
        • Contact:
        • Principal Investigator:
          • Fernanda Porto, Dr.
      • São Paulo, Brazil
        • Recruiting
        • Federal University of Sao Paulo - Hospital Sao Paulo
        • Contact:
        • Principal Investigator:
          • Juliana Sallum, Dr.
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • Not yet recruiting
        • University of Alberta
        • Contact:
        • Principal Investigator:
          • Mark Seamone, Dr.
  • Germany
      • Gießen, Germany, 35392
        • Recruiting
        • Justus-Liebig Universität - Department of Ophthalmology
        • Contact:
        • Principal Investigator:
          • Lyubomyr Lytvynchuk
      • Tübingen, Germany, 72076
        • Not yet recruiting
        • University of Tübingen - Institute for Ophthalmic Research
        • Principal Investigator:
          • Katarina Stingl, MD
        • Contact:
  • Italy
      • Naples, Italy
        • Not yet recruiting
        • Eye Clinic University of Campania Liugi Vanvitelli
        • Contact:
        • Principal Investigator:
          • Francesca Simonelli, Prof.
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Recruiting
        • Amsterdam University Medica Center - Locatie AMC
        • Contact:
        • Principal Investigator:
          • Camiel Boon
  • United Kingdom
      • London, United Kingdom, EC1V 2PD
        • Not yet recruiting
        • Moorfields Eye Hospital - NHS Foundation Trust
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 5 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1 - open label
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Names:
  • QR-110
Experimental: Group 2 - open label
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Names:
  • QR-110
Experimental: Group 3: open label
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Names:
  • QR-110
Experimental: Group 4: double-masked, randomized to one of 2 dose cohorts
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Names:
  • QR-110

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of ocular adverse events (AEs)
Time Frame: 24 months
Incidence and severity of ocular adverse events (AEs)
24 months
Incidence and severity of non-ocular adverse events (AEs)
Time Frame: 24 months
Incidence and severity of non-ocular adverse events (AEs)
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
Time Frame: 12 months
Mean change in BCVA relative to baseline after 12 months of treatment
12 months
Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)
Time Frame: 12 months
Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ProQR Therapeutics

Investigators

  • Study Director: ProQR Medical Monitor, ProQR Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

April 13, 2021

First Submitted That Met QC Criteria

April 21, 2021

First Posted (Actual)

April 22, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2022

Last Update Submitted That Met QC Criteria

March 24, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PQ-110-005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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