BRIGHTEN: 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.

Sponsor
ProQR Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04855045
Collaborator
(none)
15
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4
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Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
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.The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Mar 23, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence and severity of ocular adverse events (AEs) [24 months]

      Incidence and severity of ocular adverse events (AEs)

    2. Incidence and severity of non-ocular adverse events (AEs) [24 months]

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

    Secondary Outcome Measures

    1. Change from baseline to Month 12 in Best-corrected visual acuity (BCVA) [12 months]

      Mean change in BCVA relative to baseline after 12 months of treatment

    2. Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST) [12 months]

      Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    0 Years to 7 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Universitair Ziekenhuis Gent (UZ) Ghent Belgium 9000
    2 INRET Clinica e Centro de Pesquisa / Santa Casa BH Belo Horizonte Brazil
    3 Federal University of Sao Paulo - Hospital Sao Paulo São Paulo Brazil
    4 University of Alberta Edmonton Alberta Canada
    5 Justus-Liebig Universität - Department of Ophthalmology Gießen Germany 35392
    6 University of Tübingen - Institute for Ophthalmic Research Tübingen Germany 72076
    7 Eye Clinic University of Campania Liugi Vanvitelli Naples Italy
    8 Amsterdam University Medica Center - Locatie AMC Amsterdam Netherlands 1105 AZ
    9 Moorfields Eye Hospital - NHS Foundation Trust London United Kingdom EC1V 2PD

    Sponsors and Collaborators

    • ProQR Therapeutics

    Investigators

    • Study Director: ProQR Medical Monitor, ProQR Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    ProQR Therapeutics
    ClinicalTrials.gov Identifier:
    NCT04855045
    Other Study ID Numbers:
    • PQ-110-005
    First Posted:
    Apr 22, 2021
    Last Update Posted:
    Mar 25, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by ProQR Therapeutics
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 25, 2022