Extension Study to Study PQ-110-001 (NCT03140969) (INSIGHT)

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

Subjects completing participation in study PQ-110-001 (EudraCT 2017-000813-22 / NCT03140969) will be given the opportunity to enroll into the extension study for continued dosing if available data support current and/or future benefits for the subject. Study PQ-110-002 will provide long-term safety, tolerability, pharmacokinetic (PK), and efficacy data of QR-110.

Study Overview

• Status: Terminated
• Conditions: Eye Diseases; Neurologic Manifestations; Eye Diseases, Hereditary; Sensation Disorders; Vision Disorders; Blindness; Leber Congenital Amaurosis; Leber Congenital Amaurosis 10; Retinal Disease; Eye Disorders Congenital
• Intervention / Treatment: Drug: QR-110

Detailed Description

Subjects completing participation in study PQ-110-001 (EudraCT 2017-000813-22 / NCT03140969) will be given the opportunity to enroll into the extension study for continued dosing if available data support current and/or future benefits for the subject.

Subjects will be given the opportunity to enroll into this extension study for continued dosing if available data support current and/or future benefits for the subject. The Investigator, in consultation and agreement with the Medical Monitor, will decide on enrollment of each individual subject, as well as on dosing of the first treated eye and treatment initiation of the contralateral eye. Continued subject treatment in this study is desirable, but cannot be guaranteed, since it will depend on the risks and benefit of further treatment on a case-by-case basis, as discussed and agreed upon with the Medical Monitor.

The contralateral eye and the first treated eye will be injected 3 months apart. The injection interval of 3 months between both eyes will limit burden for the subjects, with a 3 month-visit frequency during the course of the study. This between-eye interval could be adapted if safety data are supportive, and for logistic reasons, and in agreement with the Medical Monitor.

The same safety monitoring protocol and efficacy assessments will apply to both eyes.

QR-110 will be administered via intravitreal (IVT) injection.

• Study Type: Interventional
• Enrollment (Actual): 9
• 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:

• Subjects who completed participation in the study PQ-110-001 and who may derive benefit from continued treatment with QR 110, as assessed by the Investigator, in consultation with the Medical Monitor
• Persistence of detectable outer nuclear layer (ONL) in the area of the macula in the opinion of the Investigator, as determined by OCT.
• Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.
• An adult (≥ 18 years) willing and able to provide informed consent for participation OR a minor (6 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.
• Female subjects who have reached menarche and male subjects must either practice true abstinence in accordance with their preferred and usual lifestyle, or agree to use acceptable, highly effective methods of contraception for up to 3 months following their last dose QR-110. Acceptable methods of contraception are defined in the protocol. Women of non-childbearing potential may be included without the use of adequate birth control, provided they meet the criteria in the protocol.

Exclusion Criteria:

• Any contraindication to IVT injection according to the Investigator's clinical judgment and international guidelines (Avery 2014).
• Safety issue during study PQ-110-001 that may compromise subject safety when continued dosing, as determined by the Investigator, and in consultation with the Medical Monitor.
• Any ocular or systemic disease or condition (including medications and laboratory test abnormalities) that could compromise subject safety or interfere with assessment of efficacy and safety, as determined by the Investigator and in consultation with the Medical Monitor.
• Pregnant or breast-feeding female.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug QR-110; First treated eye: maintenance dose every 6 months, intravitreal administration Contralateral eye: loading dose followed by maintenance dose, every 6 months, intravitreal administration	Drug: QR-110; First treated eye: maintenance dose every 6 months, intravitreal administration Contralateral eye: loading dose followed by maintenance dose, every 6 months, intravitreal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Ocular AEs	Frequency of ocular adverse events (AEs)	24 months
Frequency of Non-ocular AEs	Frequency of non-ocular AEs	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BCVA in First Treated Eye	Change in Best Corrected Visual Acuity (BCVA) in First Treated Eye	24 months
Change in Mobility Course Score	Change in Mobility course score	24 months
Change in Photoreceptor Outer Segment Layer Thickness	Change in photoreceptor outer segment layer thickness by Optical Coherence Tomography (OCT)	24 months
Change in OCI	Change in Oculomotor Instability (OCI)	24 months
Change in FST Blue	Change in Full-Field Stimulus Testing (FST) - blue stimuli	24 months
Change in FST Red	Change in Full-Field Stimulus Testing (FST) - red stimuli	24 months
Change in VFQ-25	Change in Visual Function Questionnaire-25 (VFQ-25) score (adult subjects)	24 months
Change in CVAQ	Change in Cardiff Visual Ability Questionnaire for Children (CVAQC) score (pediatric subjects)	24 months
Change in PLR	Change in Pupillary Light Reflex (PLR) (latency and amplitude)	24 months
Change in NIRAF	Change in Near Infrared AutoFluorescence (NIRAF)	24 months
Change in BCVA in Treated Contralateral Eye	Change in Best Corrected Visual Acuity (BCVA) in Treated Contralateral Eye	24 months
Change in BCVA in Non-Treated Contralateral Eye	Change in Best Corrected Visual Acuity (BCVA) in Non-Treated Contralateral Eye	24 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): October 3, 2022
• Study Completion (Actual): October 3, 2022

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 12, 2019

Study Record Updates

• Last Update Posted (Estimate): January 4, 2023
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Antisense oligonucleotide; CEP290; LCA10; p.Cys998X; c.2991+1655A>G; Leber's Congenital Amaurosis; RNA therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Congenital Abnormalities; Disease; Retinal Diseases; Eye Diseases; Sensation Disorders; Genetic Diseases, Inborn; Blindness; Vision Disorders; Neurologic Manifestations; Leber Congenital Amaurosis; Eye Diseases, Hereditary; Eye Abnormalities
• Other Study ID Numbers: PQ-110-002; 2018-003500-40 (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