Back to resultsA Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE) (ILLUMINATE)
Primary Purpose
Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
sepofarsen
Sham
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's Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen
Eligibility Criteria
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.
Sites / Locations
- University of Iowa
- Universitair Ziekenhuis Gent (UZ)
- INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
- Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
- The Hospital for Sick Children - SickKids
- McGill University Health Centre - Centre for Innovative Medicine
- Centre de maladies rares CHNO des Quinze Vingt
- Hospital Civil de Strasbourg
- Justus-Liebig Universität - Department of Ophthalmology
- University of Tuebingen - Inst. for Ophthalmic Research
- Eye Clinic University of Campania Luigi Vanvitelli
- Amsterdam University Medica Center - Locatie AMC
- Het Oogziekenhuis Rotterdam
- Moorfields Eye Hospital - NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Sham Comparator
Arm Label
Group 1: Dose 1 sepofarsen (QR-110)
Group 2: Dose 2 sepofarsen (QR-110)
Group 3: Sham
Arm Description
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
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
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
Outcomes
Primary Outcome Measures
Change in BCVA
Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
Secondary Outcome Measures
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
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.
Change in BCVA based on FrACT
Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)
Change in mobility course score
Change from baseline in mobility course score
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT
Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT
Change in oculomotor instability (OCI)
Change in oculomotor instability from baseline
Change in FST light sensitivity
Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)
Change in LLVA
Change from baseline in low luminance visual acuity (LLVA)
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
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
Change in the Patient Global Impressions of Severity (PGI-S)
Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
Change in the Patient Global Impressions of Change (PGI-C)
Change in the PRO Patient Global Impressions of Change (PGI-C)
Change in FAF
Change from baseline as determined by fundus autofluorescence (FAF) imaging
Changes in microperimetry
Change from baseline as determined by microperimetry
Systemic exposure to QR-110
Systemic exposure to QR-110
Ocular and non-ocular AEs
Frequency and severity of ocular and non-ocular AEs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03913143
Brief Title
A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
Acronym
ILLUMINATE
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 4, 2019 (Actual)
Primary Completion Date
January 31, 2022 (Actual)
Study Completion Date
March 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
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
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 Diseases, Hereditary, Eye Disorders Congenital, Retinal Disease
Keywords
LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber's Congenital Amaurosis, Antisense oligonucleotide, RNA therapy, QR-110, sepofarsen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: Dose 1 sepofarsen (QR-110)
Arm Type
Experimental
Arm Description
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
Arm Title
Group 2: Dose 2 sepofarsen (QR-110)
Arm Type
Active Comparator
Arm Description
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
Arm Title
Group 3: Sham
Arm Type
Sham Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
sepofarsen
Other Intervention Name(s)
QR-110
Intervention Description
RNA antisense oligonucleotide for intravitreal injection
Intervention Type
Other
Intervention Name(s)
Sham
Intervention Description
Sham-Procedure (no experimental drug administered)
Primary Outcome Measure Information:
Title
Change in BCVA
Description
Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change from baseline in BCVA ≤ -0.3 LogMAR
Description
Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline
Time Frame
12 and 24 months
Title
Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR
Description
Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.
Time Frame
12 and 24 months
Title
Change in BCVA based on FrACT
Description
Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)
Time Frame
12 and 24 months
Title
Change in mobility course score
Description
Change from baseline in mobility course score
Time Frame
12 and 24 months
Title
Change in ellipsoid zone (EZ) width/area assessed by SD-OCT
Description
Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT
Time Frame
12 and 24 months
Title
Change in oculomotor instability (OCI)
Description
Change in oculomotor instability from baseline
Time Frame
12 and 24 months
Title
Change in FST light sensitivity
Description
Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)
Time Frame
12 and 24 months
Title
Change in LLVA
Description
Change from baseline in low luminance visual acuity (LLVA)
Time Frame
12 and 24 months
Title
Change in patient reported visual function via VFQ-25 (adults)
Description
Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline
Time Frame
12 and 24 months
Title
Change in patient reported visual function via CVAQC (pediatrics)
Description
Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline
Time Frame
12 and 24 months
Title
Change in the Patient Global Impressions of Severity (PGI-S)
Description
Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
Time Frame
12 and 24 months
Title
Change in the Patient Global Impressions of Change (PGI-C)
Description
Change in the PRO Patient Global Impressions of Change (PGI-C)
Time Frame
12 and 24 months
Title
Change in FAF
Description
Change from baseline as determined by fundus autofluorescence (FAF) imaging
Time Frame
12 and 24 months
Title
Changes in microperimetry
Description
Change from baseline as determined by microperimetry
Time Frame
12 and 24 months
Title
Systemic exposure to QR-110
Description
Systemic exposure to QR-110
Time Frame
12 and 24 months
Title
Ocular and non-ocular AEs
Description
Frequency and severity of ocular and non-ocular AEs
Time Frame
12 and 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Universitair Ziekenhuis Gent (UZ)
City
Ghent
Country
Belgium
Facility Name
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
City
Belo Horizonte
State/Province
MG
ZIP/Postal Code
30150270
Country
Brazil
Facility Name
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
City
São Paulo
State/Province
SP
ZIP/Postal Code
04023-062
Country
Brazil
Facility Name
The Hospital for Sick Children - SickKids
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2L3
Country
Canada
Facility Name
McGill University Health Centre - Centre for Innovative Medicine
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Centre de maladies rares CHNO des Quinze Vingt
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hospital Civil de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Justus-Liebig Universität - Department of Ophthalmology
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Facility Name
University of Tuebingen - Inst. for Ophthalmic Research
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Eye Clinic University of Campania Luigi Vanvitelli
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Amsterdam University Medica Center - Locatie AMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Het Oogziekenhuis Rotterdam
City
Rotterdam
ZIP/Postal Code
3011 BH
Country
Netherlands
Facility Name
Moorfields Eye Hospital - NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.proqr.com
Description
Sponsor website
Learn more about this trial
A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
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