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

• ClinicalTrials.gov Identifier: NCT03913130
• Recruitment Status: Active, not recruiting
• First Posted: April 12, 2019
• Last Update Posted: February 21, 2021
• Sponsor: ProQR Therapeutics
• Information provided by (Responsible Party): ProQR Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Leber Congenital Amaurosis 10; Blindness; Leber Congenital Amaurosis; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Eye Diseases, Hereditary; Eye Disorders Congenital; Retinal Disease	Drug: QR-110	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 13, 2019
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: March 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Frequency of ocular AEs [ Time Frame: 24 months ]
   Frequency of ocular adverse events (AEs)
2. Frequency of non-ocular AEs [ Time Frame: 24 months ]
   Frequency of non-ocular AEs

Secondary Outcome Measures :

1. Change in BCVA [ Time Frame: 24 months ]
   Change in Best Corrected Visual Acuity (BCVA)
2. Change in Mobility course score [ Time Frame: 24 months ]
   Change in Mobility course score
3. Change in photoreceptor outer segment layer thickness [ Time Frame: 24 months ]
   Change in photoreceptor outer segment layer thickness by Optical Coherence Tomography (OCT)
4. Change in OCI [ Time Frame: 24 months ]
   Change in Oculomotor Instability (OCI)
5. Change in FST blue [ Time Frame: 24 months ]
   Change in Full-Field Stimulus Testing (FST) - blue stimuli
6. Change in FST red [ Time Frame: 24 months ]
   Change in Full-Field Stimulus Testing (FST) - red stimuli
7. Change in VFQ-25 [ Time Frame: 24 months ]
   Change in Visual Function Questionnaire-25 (VFQ-25) score (adult subjects)
8. Change in CVAQ [ Time Frame: 24 months ]
   Change in Cardiff Visual Ability Questionnaire for Children (CVAQC) score (pediatric subjects)
9. Change in PLR [ Time Frame: 24 months ]
   Change in Pupillary Light Reflex (PLR) (latency and amplitude)
10. Change in NIRAF [ Time Frame: 24 months ]
    Change in Near Infrared AutoFluorescence (NIRAF)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Pennsylvania

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Belgium

Ghent University Hospital and Ghent University

Ghent, Belgium, B-9000

Sponsors and Collaborators

ProQR Therapeutics

Investigators

• Study Director: ProQR Medical Monitor; ProQR Therapeutics

More Information

Additional Information:

Sponsor website 

• Responsible Party: ProQR Therapeutics
• ClinicalTrials.gov Identifier: NCT03913130
• Other Study ID Numbers: PQ-110-002
• First Posted: April 12, 2019
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by ProQR Therapeutics:

LCA10; CEP290; p.Cys998X; c.2991+1655A>G; Leber's Congenital Amaurosis; Antisense oligonucleotide; RNA therapy

Additional relevant MeSH terms:

Blindness; Neurologic Manifestations; Vision Disorders; Sensation Disorders; Eye Diseases; Retinal Diseases; Leber Congenital Amaurosis; Eye Diseases, Hereditary; Eye Abnormalities; Genetic Diseases, Inborn; Disease; Pathologic Processes; Nervous System Diseases; Congenital Abnormalities