Study to Evaluate QR-110 in Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Sponsor

ProQR Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT03140969

Collaborator

(none)

Enrollment

Locations

Arm

23.5

Actual Duration (Months)

3.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.

Condition or Disease	Intervention/Treatment	Phase
Leber's Congenital Amaurosis	Drug: QR-110	Phase 1/Phase 2

Detailed Description

The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Actual Study Start Date :

Oct 16, 2017

Actual Primary Completion Date :

Oct 2, 2019

Actual Study Completion Date :

Oct 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QR-110 Administered every 3 months	Drug: QR-110 RNA antisense oligonucleotide for intravitreal injection

Arm

Intervention/Treatment

Experimental: QR-110

Administered every 3 months

Drug: QR-110

RNA antisense oligonucleotide for intravitreal injection

Outcome Measures

Primary Outcome Measures

Frequency and severity of ocular adverse events in the treatment and contralateral eyes [1 year]

Secondary Outcome Measures

Frequency and severity of non-ocular adverse events [1 year]
Change in ophthalmic examination findings [1 year]
Change in best-corrected visual acuity (BCVA) [1 year]
Change in infrared imaging [1 year]
Change in optical coherence tomography (OCT) findings [1 year]
Changes in safety parameters, including vital sign measurements, physical examination findings, ECG and laboratory parameters [1 year]
Area under the curve 0 hour to infinity [AUC(0-∞)] of QR-110 in serum (if measurable) [1 year]
Area under the curve 0 hour to time of the last measurable concentration [AUC(0-t)] of QR-110 in serum [1 year]
Maximum concentration (Cmax ) of QR-110 in serum [1 year]
Minimum concentration (Cmin) of QR-110 in serum [1 year]
Time of maximum concentration (Tmax ) of QR-110 in serum [1 year]
Terminal half life (T1/2) of QR-110 in serum (if measurable) [1 year]
Clearance (CL) of QR-110 in serum (if measurable) [1 year]
Volume of distribution (Vd) of QR-110 in serum (if measurable) [1 year]
Change in full-field stimulus test (FST) [1 year]
Change in pupillary light reflex (PLR) [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, ≥ 6 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.
Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye.
Detectable outer nuclear layer (ONL) in the area of the macula.
An electroretinogram (ERG) result consistent with LCA.
Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.

Exclusion Criteria:

Syndromic disease.
Pregnant or breast-feeding female.
Any clinically significant cardiac disease or defect.
One or more coagulation parameters outside of the normal range.
Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety.
Prior receipt of intraocular surgery or intravitreal injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study.
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-110-001 study period.
Any prior receipt of genetic therapy for LCA

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242
2	Scheie Eye Institute, University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
3	Ghent University Hospital and Ghent University	Ghent		Belgium	B-9000