Back to resultsAn 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)
Primary Purpose
Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
sepofarsen
Sponsored by
About this trial
This is an interventional treatment trial for Leber Congenital Amaurosis 10 focused on measuring LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen, pediatric, children
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.
Sites / Locations
- Universitair Ziekenhuis Gent (UZ)Recruiting
- INRET Clinica e Centro de Pesquisa / Santa Casa BHRecruiting
- Federal University of Sao Paulo - Hospital Sao PauloRecruiting
- University of Alberta
- Justus-Liebig Universität - Department of OphthalmologyRecruiting
- University of Tübingen - Institute for Ophthalmic Research
- Eye Clinic University of Campania Liugi Vanvitelli
- Amsterdam University Medica Center - Locatie AMCRecruiting
- Moorfields Eye Hospital - NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1 - open label
Group 2 - open label
Group 3: open label
Group 4: double-masked, randomized to one of 2 dose cohorts
Arm Description
Outcomes
Primary Outcome Measures
Incidence and severity of ocular adverse events (AEs)
Incidence and severity of ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs)
Secondary Outcome Measures
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
Mean change in BCVA relative to baseline after 12 months of treatment
Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)
Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04855045
Brief Title
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.
Acronym
BRIGHTEN
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ProQR Therapeutics
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Model Description
The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1 - open label
Arm Type
Experimental
Arm Title
Group 2 - open label
Arm Type
Experimental
Arm Title
Group 3: open label
Arm Type
Experimental
Arm Title
Group 4: double-masked, randomized to one of 2 dose cohorts
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
sepofarsen
Other Intervention Name(s)
QR-110
Intervention Description
RNA antisense oligonucleotide for intravitreal injection
Primary Outcome Measure Information:
Title
Incidence and severity of ocular adverse events (AEs)
Description
Incidence and severity of ocular adverse events (AEs)
Time Frame
24 months
Title
Incidence and severity of non-ocular adverse events (AEs)
Description
Incidence and severity of non-ocular adverse events (AEs)
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
Description
Mean change in BCVA relative to baseline after 12 months of treatment
Time Frame
12 months
Title
Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)
Description
Mean change in retinal sensitivity measured by FST relative to baseline after 12 months of treatment
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ProQR Clinical Trials Manager
Phone
+31881667000
Email
info@proqr.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ProQR Medical Monitor
Organizational Affiliation
ProQR Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Universitair Ziekenhuis Gent (UZ)
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bart Leroy
Email
bart.leroy@ugent.be
First Name & Middle Initial & Last Name & Degree
Bart Leroy
Facility Name
INRET Clinica e Centro de Pesquisa / Santa Casa BH
City
Belo Horizonte
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernanda Porto, Dr.
Phone
00553132264882
Email
pesquisa@inret.com.br
First Name & Middle Initial & Last Name & Degree
Fernanda Porto, Dr.
Facility Name
Federal University of Sao Paulo - Hospital Sao Paulo
City
São Paulo
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juliana Sallum
Phone
00551155764848
Ext
2265
Email
juliana@pobox.com
First Name & Middle Initial & Last Name & Degree
Juliana Sallum, Dr.
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rita Whitford
Phone
0017804928869
Email
ovstrial@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Mark Seamone, Dr.
Facility Name
Justus-Liebig Universität - Department of Ophthalmology
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lyubomyr Lytvynchuk
Phone
+49-641-985-43803
Email
lyubomyr.Lytvynchuk@augen.med.uni-giessen.de
First Name & Middle Initial & Last Name & Degree
Lyubomyr Lytvynchuk
Facility Name
University of Tübingen - Institute for Ophthalmic Research
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Rindtorff
Phone
+49 7071 29 87747
Email
andrea.rindtorff@stz-eyetrial.de
First Name & Middle Initial & Last Name & Degree
Katarina Stingl, MD
Facility Name
Eye Clinic University of Campania Liugi Vanvitelli
City
Naples
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesca Simonelli, Prof.
Phone
00393387630132
Email
francesca.simonelli@unicampania.it
First Name & Middle Initial & Last Name & Degree
Francesca Simonelli, Prof.
Facility Name
Amsterdam University Medica Center - Locatie AMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monique Wezel
Phone
+31 205668618
Email
m.wezel@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Camiel Boon
Facility Name
Moorfields Eye Hospital - NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Flora Kakanou
Phone
+44 0207 253 3411
Ext
2109
Email
flora.kakanou@nhs.net
First Name & Middle Initial & Last Name & Degree
Michel Michaelides
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.proqr.com
Description
Sponsor website
Learn more about this trial
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.
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