Leber Congenital Amaurosis 10Phase 2/3ILLUMINATENCT03913143
A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
A Phase 2/3 study testing sepofarsen in people with Leber Congenital Amaurosis 10 and Blindness, run by ProQR Therapeutics at 14 sites in 9 countries.
Trial summary
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months… Read more about this study
- Who is it for?
- Ages 8 years and older
- 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?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 14 sitesin 9 countries
- Study dates
- 4 Apr 2019to Mar 2023
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Main Inclusion Criteria Relating to Study Initiation:
- Male or female, ≥ 8 years of age at Screening with a clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation, based on genotyping analysis at Screening. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval.
- BCVA better or equal to Logarithm of the Minimum Angle of Resolution (LogMAR) +3.0 (Hand Motion), and equal to or worse than LogMAR +0.4 in the treatment eye.
- Detectable outer nuclear layer (ONL) in the area of the macula.
- An electroretinogram (ERG) result consistent with LCA. A historic ERG result may be acceptable for eligibility.
Main Exclusion Criteria Relating to Study Initiation:
- Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities).
- Prior receipt of intraocular surgery, periocular surgery, or IVT injection within 1 month prior to study start or planned intraocular surgery or procedure during the course of the study.Subjects who received an intraocular or periocular surgery between 1 to 3 months prior Screening, may only be considered for inclusion if there are no clinically significant complications of surgery present, and following approval by the Medical Monitor.
- History or presence of ocular herpetic diseases.
- Presence of any active ocular infection in the either eye.
- Presence of lens opacities/cataracts in the treatment eye.
- Current treatment or treatment within the past 12 months with therapies known to influence the immune system.
- History of glaucoma, or an IOP greater than 24 mmHg, at is not controlled with medication.
- History of amblyopia
- Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the PQ-110-003 study period.
- Any prior receipt of genetic or stem-cell therapy.
- Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
- Pregnant and breastfeeding subjects.
Main Inclusion Criteria Relating to Treatment Initiation Contralateral Eye:
- BCVA equal to or better than LP (logMAR +4), using the best BCVA reading at Month 12 and based on ETDRS or BRVT.
- Detectable outer nuclear layer (ONL) in the area of the macula.
- Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.
Main Exclusion Criteria Relating to Treatment Initiation Contralateral Eye:
- Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities).
- History or presence of ocular herpetic diseases.
- Presence of any active ocular infection in either eye.
- Presence of any lens opacities which are clinically significant, would adequately prevent clinical and photographic evaluation of the retina.
- A planned IVT injection or intraocular or periocular surgery/procedure (including refractive surgery) during the course of the study.
- A history of glaucoma or an IOP greater than 24 mmHg that is not controlled with medication.
- History of amblyopia.
- Plans to participate in another study of a drug or device during the study period.
- Pregnant and breastfeeding subjects.
Trial locations and contacts
14 sites in 9 countries.
14 sites in 9 countries
Brazil2 sites
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150270
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
São Paulo, São Paulo, 04023-062
Canada2 sites
McGill University Health Centre - Centre for Innovative Medicine
Montreal, Quebec, H4A 3J1
The Hospital for Sick Children - SickKids
Toronto, Ontario, M5G 2L3
France2 sites
Centre de maladies rares CHNO des Quinze Vingt
Paris, 75012
Hospital Civil de Strasbourg
Strasbourg, 67091
Germany2 sites
Justus-Liebig Universität - Department of Ophthalmology
Giessen, 35392
University of Tuebingen - Inst. for Ophthalmic Research
Tübingen, 72076
Netherlands2 sites
Amsterdam University Medica Center - Locatie AMC
Amsterdam, 1105 AZ
Het Oogziekenhuis Rotterdam
Rotterdam, 3011 BH
United Kingdom1 site
Moorfields Eye Hospital - NHS Foundation Trust
London, EC1V 2PD
About this study
Official title: Double-masked, Randomized, Controlled, Multiple-dose Study to Evaluate Efficacy, Safety, Tolerability and Syst. Exposure of QR-110 in Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment
Read the detailed description
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment.
At study start subjects will be randomized to one of 3 treatment groups with either active study drug or sham treatment.
Sepofarsen (QR-110) will be administered via intravitreal (IVT) injection into the subject's treatment eye (the subject's worse eye).
Subjects in the sham-procedure group will undergo a procedure that will closely mimic the active injection.
After each dosing subjects will be assessed for safety and tolerability at follow up visits.
After the first eye has been treated for at least 12 months, treatment of the contralateral eye and cross-over of subjects assigned to sham procedure may be initiated in eligible eyes (in a masked manner) based on assessment of benefit/risk (including review of data from all clinical trials), and with concurrence of the Medical Monitor.
- Conditions
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations
- Being tested
- sepofarsen, Sham
- Keywords
- LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber's Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen
- Medical subject headings
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations, Eye Diseases, Eye Diseases, Hereditary
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
ShamOther
Sham-Procedure (no experimental drug administered)
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Dose 1 sepofarsen (QR-110) | Experimental | Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated Receives: Drug: sepofarsen |
| Group 2: Dose 2 sepofarsen (QR-110) | Active comparator | Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated Receives: Drug: sepofarsen |
| Group 3: Sham | Sham comparator | Sham procedure (no experimental drug administered), Day 1, month 3 and every six months there after. After 12 months cross over to active study drug may be initiated Receives: Other: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in BCVA
Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
Measured: 12 months
Secondary outcomes (16)
Change from baseline in BCVA ≤ -0.3 LogMAR
Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline
Measured: 12 and 24 months
Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR
Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.
Measured: 12 and 24 months
Change in BCVA based on FrACT
Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)
Measured: 12 and 24 months
Change in mobility course score
Change from baseline in mobility course score
Measured: 12 and 24 months
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT
Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT
Measured: 12 and 24 months
Change in oculomotor instability (OCI)
Change in oculomotor instability from baseline
Measured: 12 and 24 months
Change in FST light sensitivity
Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)
Measured: 12 and 24 months
Change in LLVA
Change from baseline in low luminance visual acuity (LLVA)
Measured: 12 and 24 months
Change in patient reported visual function via VFQ-25 (adults)
Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline
Measured: 12 and 24 months
Change in patient reported visual function via CVAQC (pediatrics)
Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline
Measured: 12 and 24 months
Change in the Patient Global Impressions of Severity (PGI-S)
Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
Measured: 12 and 24 months
Change in the Patient Global Impressions of Change (PGI-C)
Change in the PRO Patient Global Impressions of Change (PGI-C)
Measured: 12 and 24 months
Change in FAF
Change from baseline as determined by fundus autofluorescence (FAF) imaging
Measured: 12 and 24 months
Changes in microperimetry
Change from baseline as determined by microperimetry
Measured: 12 and 24 months
Systemic exposure to QR-110
Systemic exposure to QR-110
Measured: 12 and 24 months
Ocular and non-ocular AEs
Frequency and severity of ocular and non-ocular AEs
Measured: 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2019
- Study start4 Apr 2019
- Primary completion31 Jan 2022
- Study completionMar 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
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
- NCT03913143
- Sponsor's protocol ID
- PQ-110-003
- Other IDs
- 2018-003501-25, 2018
- Acronym
- ILLUMINATE
- Status last verified
- Feb 2022
- First submitted
- 21 Feb 2019
- Last updated
- 17 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-masked, Randomized, Controlled, Multiple-dose Study to Evaluate Efficacy, Safety, Tolerability and Syst. Exposure of QR-110 in Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
- ClinicalTrials.gov ID
- NCT03913143
- Acronym / sponsor ID
- ILLUMINATE / PQ-110-003
- 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's Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (actual)
- Lead sponsor
- ProQR TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- Mar 2023 (estimated)
- First posted
- 12 Apr 2019 (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.
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment
Detailed description
The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment.
At study start subjects will be randomized to one of 3 treatment groups with either active study drug or sham treatment.
Sepofarsen (QR-110) will be administered via intravitreal (IVT) injection into the subject's treatment eye (the subject's worse eye).
Subjects in the sham-procedure group will undergo a procedure that will closely mimic the active injection.
After each dosing subjects will be assessed for safety and tolerability at follow up visits.
After the first eye has been treated for at least 12 months, treatment of the contralateral eye and cross-over of subjects assigned to sham procedure may be initiated in eligible eyes (in a masked manner) based on assessment of benefit/risk (including review of data from all clinical trials), and with concurrence of the Medical Monitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Dose 1 sepofarsen (QR-110) | Experimental | Drug: sepofarsenInitial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated |
| Group 2: Dose 2 sepofarsen (QR-110) | Active comparator | Drug: sepofarsenInitial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated |
| Group 3: Sham | Sham comparator | Other: ShamSham procedure (no experimental drug administered), Day 1, month 3 and every six months there after. After 12 months cross over to active study drug may be initiated |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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: Dose 1 sepofarsen (QR-110), Group 2: Dose 2 sepofarsen (QR-110) |
| ShamSham-Procedure (no experimental drug administered) | Other | Group 3: Sham |
Primary outcome
Change in BCVA
Time frame: 12 months
Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
16 secondary outcomes
Change from baseline in BCVA ≤ -0.3 LogMAR
Time frame: 12 and 24 months
Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR
Time frame: 12 and 24 months
Change in BCVA based on FrACT
Time frame: 12 and 24 months
Change in mobility course score
Time frame: 12 and 24 months
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT
Time frame: 12 and 24 months
Change in oculomotor instability (OCI)
Time frame: 12 and 24 months
Change in FST light sensitivity
Time frame: 12 and 24 months
Change in LLVA
Time frame: 12 and 24 months
Change in patient reported visual function via VFQ-25 (adults)
Time frame: 12 and 24 months
Change in patient reported visual function via CVAQC (pediatrics)
Time frame: 12 and 24 months
Change in the Patient Global Impressions of Severity (PGI-S)
Time frame: 12 and 24 months
Change in the Patient Global Impressions of Change (PGI-C)
Time frame: 12 and 24 months
Change in FAF
Time frame: 12 and 24 months
Changes in microperimetry
Time frame: 12 and 24 months
Systemic exposure to QR-110
Time frame: 12 and 24 months
Ocular and non-ocular AEs
Time frame: 12 and 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
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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
14 sites in 9 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 14 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: under way, not looking for participants, as of the sponsor's last update on 17 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 14 sites in Brazil, Canada, France, Germany, Netherlands and 4 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in BCVA (time frame: 12 months). 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 17 Mar 2022.