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

• ClinicalTrials.gov Identifier: NCT03140969
• Recruitment Status: Completed
• First Posted: May 4, 2017
• Last Update Posted: October 19, 2020
• Sponsor: ProQR Therapeutics
• Information provided by (Responsible Party): ProQR Therapeutics

Tracking Information

• First Submitted Date: May 1, 2017
• First Posted Date: May 4, 2017
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: October 16, 2017
• Actual Primary Completion Date: October 2, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 3, 2017): Frequency and severity of ocular adverse events in the treatment and contralateral eyes [ Time Frame: 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 29, 2017)

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

Original Secondary Outcome Measures (submitted: May 3, 2017)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Leber's Congenital Amaurosis

Intervention

Drug: QR-110

RNA antisense oligonucleotide for intravitreal injection

Study Arms

Experimental: QR-110

Administered every 3 months

Intervention: Drug: QR-110

Publications *

• 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 Apr 1. doi: 10.1038/s41591-021-01297-7. [Epub ahead of print]
• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 9, 2020): 11
• Original Estimated Enrollment (submitted: May 3, 2017): 12
• Actual Study Completion Date: October 2, 2019
• Actual Primary Completion Date: October 2, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, United States

Administrative Information

• NCT Number: NCT03140969
• Other Study ID Numbers: PQ-110-001; 2017-000813-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: ProQR Therapeutics
• Study Sponsor: ProQR Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: ProQR Study Director; ProQR Therapeutics

• PRS Account: ProQR Therapeutics
• Verification Date: October 2020