A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety, Tolerability and Systemic Exposure of QR-110 in Subjects with Leber*s Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
- Conditions
- Lebers Congenital Amaurosis. Leber's Disease1001592010010463
- Registration Number
- NL-OMON55773
- Lead Sponsor
- ProQR Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
Relating to Study Initiation : The subject is eligible for the study and thus
eligible to receive QR-110 or fake-procedure in the treatment eye (ie, the
first eye to be treated) if all the following inclusion criteria apply at
Screening/Day 1:
1. An adult (>= 18 years) willing and able to provide informed consent for
participation -OR- a minor (8 to < 18 years) with a parent or legal guardian
willing and able to provide written permission for the subject*s participation
prior to performing any study related procedures and pediatric subjects able to
provide age appropriate assent for study participation.
2. Male or female, >= 8 years of age at screening with a clinical diagnosis of
LCA and a molecular diagnosis of homozygosity or compound heterozygosity for
the c.2991+1655A>G mutation, based on genotyping analysis at Screening.
Historic genotyping report from a certified laboratory is acceptable with
Sponsor approval.
3. BCVA better or equal to Logarithm of the Minimum Angle of Resolution
(logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate
Snellen equivalent 20/50) in the treatment eye, using the best BCVA reading at
Screening and based on the Early Treatment Diabetic Retinopathy Study (ETDRS)
or the Berkeley rudimentary vision test (BRVT).
4. Detectable outer nuclear layer (ONL) in the area of the macula as determined
by the Investigator at Screening.
5. An electroretinogram (ERG) result consistent with LCA, as determined by the
Investigator. A historic ERG result may be acceptable for eligibility.
6. Clear ocular media and adequate pupillary dilation to permit good quality
retinal imaging, as assessed by the Investigator.
7. Non-pregnant and non-breastfeeding subjects.
Relating to Treatment Initiation Contralateral Eye:
1. BCVA better or equal to Logarithm of the Minimum Angle of Resolution
(logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate
Snellen equivalent 20/50) in the contralateral eye, using the best BCVA reading
at Month 12 (see Section 8.1) and based on the
Early Treatment Diabetic Retinopathy Study (ETDRS) or the Berkeley Rudimentary
Vision Test (BRVT).
2. Detectable outer nuclear layer (ONL) in the area of the macula of the
contralateral eye as determined by the Investigator.
3. Clear ocular media and adequate pupillary dilation to permit good quality
retinal imaging in the contralateral eye, as assessed by the Investigator.
4. Non-pregnant and non-breastfeeding subjects.
Relating to Study Initiation : The subject is ineligible for the study if any
of the following criteria apply at Screening/Day 1:
1. Presence of any significant ocular or non-ocular disease/disorder (including
medication and laboratory test abnormalities) which, in the opinion of the
Investigator and with concurrence of the Medical Monitor, may either put the
subject at risk because of participation in the study, may influence the
results of the study, or the subject*s ability to participate in the study.
2. 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 study period.
3. Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular
disease.
4. 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 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.
5. Known hypersensitivity to antisense oligonucleotides or any constituents of
the injection.
6. Pregnant and breastfeeding subjects.
Relating to Treatment Initiation Contralateral Eye:
1. Presence of any significant ocular or non-ocular disease/disorder (including
medication and laboratory test abnormalities) which, in the opinion of the
Investigator and with concurrence of the Medical Monitor, may either put the
subject at risk because of participation in the study, may influence the
results of the study, or the subject's ability to participate in the study.
This includes but is not limited a subject who: 1)
is not an appropriate candidate for antisense oligonucleotide treatment,
2) has concurrent cystoid macular edema (CME) in the contralateral eye.
2. A planned IVT injection or intraocular or periocular
surgery/procedure (including refractive surgery) in the contralateral eye
during the course of the study.
3. Plans to participate in another study of a drug or device during the
study period.
4. Pregnant and breastfeeding subjects.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The change from baseline in BCVA (based on ETDRS and/or BRVT) at 12 months of<br /><br>treatment versus sham-procedure</p><br>
- Secondary Outcome Measures
Name Time Method