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

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

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.

Study Overview

• Status: Completed
• Conditions: Leber's Congenital Amaurosis
• Intervention / Treatment: Drug: QR-110

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, B-9000
    • Ghent University Hospital and Ghent University
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Scheie Eye Institute, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QR-110; Administered every 3 months	Drug: QR-110; RNA antisense oligonucleotide for intravitreal injection; Other Names: Sepofarsen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Severity of Non-ocular Adverse Events		1 year
Change in Best-corrected Visual Acuity (BCVA)		1 year
Change in Full-field Stimulus Test (FST)	Average Red Light Score	1 year
Change in Full-field Stimulus Test (FST)	Average Blue Light Score	1 year

Collaborators and Investigators

• Sponsor: ProQR Therapeutics
• Investigators: Study Director: ProQR Study Director, ProQR Therapeutics

Publications and helpful links

General Publications

• Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.
• Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial. Nat Med. 2022 May;28(5):1014-1021. doi: 10.1038/s41591-022-01755-w. Epub 2022 Apr 4.
• Cideciyan AV, Jacobson SG, Ho AC, Garafalo AV, Roman AJ, Sumaroka A, Krishnan AK, Swider M, Schwartz MR, Girach A. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report. Nat Med. 2021 May;27(5):785-789. doi: 10.1038/s41591-021-01297-7. Epub 2021 Apr 1.
• Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, Roman AJ, Sumaroka A, Han IC, Hochstedler MD, Pfeifer WL, Sohn EH, Taiel M, Schwartz MR, Biasutto P, Wit W, Cheetham ME, Adamson P, Rodman DM, Platenburg G, Tome MD, Balikova I, Nerinckx F, Zaeytijd J, Van Cauwenbergh C, Leroy BP, Russell SR. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019 Feb;25(2):225-228. doi: 10.1038/s41591-018-0295-0. Epub 2018 Dec 17.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): October 2, 2019
• Study Completion (Actual): October 2, 2019

Study Registration Dates

• First Submitted: May 1, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): December 27, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Antisense oligonucleotide; CEP290; p.Cys998X; c.2991+1655A>G; RNA therapy; Leber's congenital amaurosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Diseases; Eye Diseases, Hereditary; Sensation Disorders; Vision Disorders; Blindness; Leber Congenital Amaurosis
• Other Study ID Numbers: PQ-110-001; 2017-000813-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No