Leber Congenital Amaurosis 10Phase 2/3BRIGHTENNCT04855045
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.
A Phase 2/3 study testing sepofarsen in people with Leber Congenital Amaurosis 10 and Blindness, run by ProQR Therapeutics at 9 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 7 years
- Conditions the study is for
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis
- What is being tested?
- sepofarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 9 sitesin 7 countries
- Study dates
- 23 Mar 2021to Dec 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
Brazil2 sites, 2 recruiting
- Recruiting
INRET Clinica e Centro de Pesquisa / Santa Casa BH
Belo Horizonte
Fernanda Porto, Dr., 00553132264882, pesquisa@inret.com.br
Fernanda Porto, Dr.
- Recruiting
Federal University of Sao Paulo - Hospital Sao Paulo
São Paulo
Juliana Sallum, 00551155764848 ext. 2265, juliana@pobox.com
Juliana Sallum, Dr.
Germany2 sites, 2 recruiting
- Recruiting
Justus-Liebig Universität - Department of Ophthalmology
Giessen, 35392
Lyubomyr Lytvynchuk, +49-641-985-43803, lyubomyr.Lytvynchuk@augen.med.uni-giessen.de
Lyubomyr Lytvynchuk
- Not yet recruiting
University of Tübingen - Institute for Ophthalmic Research
Tübingen, 72076
Andrea Rindtorff, +49 7071 29 87747, andrea.rindtorff@stz-eyetrial.de
Katarina Stingl, MD
Belgium1 site, 1 recruiting
- Recruiting
Universitair Ziekenhuis Gent (UZ)
Ghent, 9000
Bart Leroy, bart.leroy@ugent.be
Bart Leroy
Canada1 site, 1 recruiting
- Not yet recruiting
University of Alberta
Edmonton, Alberta
Rita Whitford, 0017804928869, ovstrial@ualberta.ca
Mark Seamone, Dr.
Italy1 site, 1 recruiting
- Not yet recruiting
Eye Clinic University of Campania Liugi Vanvitelli
Naples
Francesca Simonelli, Prof., 00393387630132, francesca.simonelli@unicampania.it
Francesca Simonelli, Prof.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam University Medica Center - Locatie AMC
Amsterdam, 1105 AZ
Monique Wezel, +31 205668618, m.wezel@amsterdamumc.nl
Camiel Boon
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Moorfields Eye Hospital - NHS Foundation Trust
London, EC1V 2PD
Flora Kakanou, +44 0207 253 3411 ext. 2109, flora.kakanou@nhs.net
Michel Michaelides
About this study
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.
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.
Read the 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.
- Conditions
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations
- Being tested
- sepofarsen
- Keywords
- LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen, pediatric, children
- Medical subject headings
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations, Eye Diseases, Eye Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sepofarsenDrug
Also called QR-110
RNA antisense oligonucleotide for intravitreal injection
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - open label | Experimental | Not described Receives: Drug: sepofarsen |
| Group 2 - open label | Experimental | Not described Receives: Drug: sepofarsen |
| Group 3: open label | Experimental | Not described Receives: Drug: sepofarsen |
| Group 4: double-masked, randomized to one of 2 dose cohorts | Experimental | Not described Receives: Drug: sepofarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of ocular adverse events (AEs)
Incidence and severity of ocular adverse events (AEs)
Measured: 24 months
Incidence and severity of non-ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs)
Measured: 24 months
Secondary outcomes (2)
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
Mean change in BCVA relative to baseline after 12 months of treatment
Measured: 12 months
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start23 Mar 2021
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leber Congenital Amaurosis 10Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ProQR Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ProQR Medical Monitor, Study director, ProQR Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04855045
- Sponsor's protocol ID
- PQ-110-005
- Acronym
- BRIGHTEN
- Status last verified
- Mar 2022
- First submitted
- 13 Apr 2021
- Last updated
- 25 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04855045
- Acronym / sponsor ID
- BRIGHTEN / PQ-110-005
- Conditions
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations
- Keywords
- LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- ProQR TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 22 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- The study consists of two parts: an open-label dose escalation part, followed by a double-masked randomized part.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 0 to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sepofarsenAlso: QR-110RNA antisense oligonucleotide for intravitreal injection | Drug | Group 1 - open label, Group 2 - open label, Group 3: open label, Group 4: double-masked, randomized to one of 2 dose cohorts |
Primary outcome
Incidence and severity of ocular adverse events (AEs)
Time frame: 24 months
Incidence and severity of ocular adverse events (AEs)
Incidence and severity of non-ocular adverse events (AEs)
Time frame: 24 months
Incidence and severity of non-ocular adverse events (AEs)
2 secondary outcomes
Change from baseline to Month 12 in Best-corrected visual acuity (BCVA)
Time frame: 12 months
Change from baseline to Month 12 in retinal sensitivity measured by Full-field stimulus testing (FST)
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2022.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Leber Congenital Amaurosis 10
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Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 2/3
A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ProQR Medical Monitor study director
ProQR Therapeutics
9 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing sepofarsen in people with Leber Congenital Amaurosis 10 and Blindness, run by ProQR Therapeutics at 9 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Brazil, Germany, Belgium, Canada, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact ProQR Clinical Trials Manager (+31881667000, info@proqr.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of ocular adverse events (AEs) (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2022.