Study to evaluate the efficacy, safety, tolerability and the extent to which the study drug is distributed in the body of multiple doses of QR-110 in subjects with LCA10 compared to a sham procedure. The study will be double-masked, randomized and controlled which means that both patients and study staff will not know and cannot influence who receives which treatment (study drug of sham).

Phase 1

Active, not recruiting

• Conditions: eber’s Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene; MedDRA version: 20.0Level: PTClassification code 10070667Term: Leber's congenital amaurosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2018-003501-25-GB
• Lead Sponsor: ProQR Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-24
• Last Update Posted: 2024-09-09

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Relating to Study Initiation: The subject is eligible for the study and thus eligible to receive QR-110 or sham-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 CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are 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 (see Section 8.1) 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 (see Section 8.1).
6. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.
7. An adult willing to comply with the protocol, follow study instructions, attend study visits as required and willing and able to complete all study assessments, in the opinion of the Investigator -OR- a minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions and attend study visits with the subject as required, in the opinion of the Investigator.

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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. 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 treatment eye.
2. History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in the treatment eye.
3. Presence of any active ocular infection in either eye.
4. Receipt within 3 months 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.
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,
5. Presence of any of the following lens opacities in the treatment eye: cortical opacity = +2, posterior subcapsular opacity = +2, or a nuclear sclerosis = +2, and which are: 1) clinically significant in the opinion of the Investigator, 2) would adequately prevent clinical and photographic evaluation of the retina.
6. Receipt within 3 months 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.
7. 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). Subjects that have been treated with systemic steroids within the past 12 months or that require intermittent use of topical steroids may be considered for inclusion following approval by the Medical Monitor.
8. A history of glaucoma or an IOP greater than 24 mmHg in the treatment eye that is not controlled with medication at the time of informed consent.
9. History of amblyopia in the treatment eye.
10. Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plan

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified