Back to results

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

Primary Purpose

Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

QR-110

About this trial

This is an interventional treatment trial for Leber Congenital Amaurosis 10 focused on measuring LCA10, CEP290, p.Cys998X, c.2991+1655A>G, Leber's Congenital Amaurosis, Antisense oligonucleotide, RNA therapy

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Iowa
Scheie Eye Institute, University of Pennsylvania
Ghent University Hospital and Ghent University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Drug QR-110

Arm Description

First treated eye: maintenance dose every 6 months, intravitreal administration Contralateral eye: loading dose followed by maintenance dose, every 6 months, intravitreal administration

Outcomes

Primary Outcome Measures

Frequency of Ocular AEs

Frequency of ocular adverse events (AEs)

Frequency of Non-ocular AEs

Frequency of non-ocular AEs

Secondary Outcome Measures

Change in BCVA in First Treated Eye

Change in Best Corrected Visual Acuity (BCVA) in First Treated Eye

Change in Mobility Course Score

Change in Mobility course score

Change in Photoreceptor Outer Segment Layer Thickness

Change in photoreceptor outer segment layer thickness by Optical Coherence Tomography (OCT)

Change in OCI

Change in Oculomotor Instability (OCI)

Change in FST Blue

Change in Full-Field Stimulus Testing (FST) - blue stimuli

Change in FST Red

Change in Full-Field Stimulus Testing (FST) - red stimuli

Change in VFQ-25

Change in Visual Function Questionnaire-25 (VFQ-25) score (adult subjects)

Change in CVAQ

Change in Cardiff Visual Ability Questionnaire for Children (CVAQC) score (pediatric subjects)

Change in PLR

Change in Pupillary Light Reflex (PLR) (latency and amplitude)

Change in NIRAF

Change in Near Infrared AutoFluorescence (NIRAF)

Change in BCVA in Treated Contralateral Eye

Change in Best Corrected Visual Acuity (BCVA) in Treated Contralateral Eye

Change in BCVA in Non-Treated Contralateral Eye

Change in Best Corrected Visual Acuity (BCVA) in Non-Treated Contralateral Eye

Full Information

NCT ID

NCT03913130

First Posted

February 21, 2019

Last Updated

December 9, 2022

Sponsor

ProQR Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT03913130

Brief Title

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

Acronym

INSIGHT

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Terminated

Why Stopped

Terminated [Study prematurely terminated due to sponsor decision for reasons unrelated to safety]

Study Start Date

May 13, 2019 (Actual)

Primary Completion Date

October 3, 2022 (Actual)

Study Completion Date

October 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ProQR Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Vision Disorders, Sensation Disorders, Neurologic Manifestations, Eye Diseases, Eye Diseases, Hereditary, Eye Disorders Congenital, Retinal Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Drug QR-110

Arm Type

Experimental

Arm Description

First treated eye: maintenance dose every 6 months, intravitreal administration Contralateral eye: loading dose followed by maintenance dose, every 6 months, intravitreal administration

Intervention Type

Drug

Intervention Name(s)

QR-110

Intervention Description

First treated eye: maintenance dose every 6 months, intravitreal administration Contralateral eye: loading dose followed by maintenance dose, every 6 months, intravitreal administration

Primary Outcome Measure Information:

Title

Frequency of Ocular AEs

Description

Frequency of ocular adverse events (AEs)

Time Frame

24 months

Title

Frequency of Non-ocular AEs

Description

Frequency of non-ocular AEs

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Change in BCVA in First Treated Eye

Description

Change in Best Corrected Visual Acuity (BCVA) in First Treated Eye

Time Frame

24 months

Title

Change in Mobility Course Score

Description

Change in Mobility course score

Time Frame

24 months

Title

Change in Photoreceptor Outer Segment Layer Thickness

Description

Change in photoreceptor outer segment layer thickness by Optical Coherence Tomography (OCT)

Time Frame

24 months

Title

Change in OCI

Description

Change in Oculomotor Instability (OCI)

Time Frame

24 months

Title

Change in FST Blue

Description

Change in Full-Field Stimulus Testing (FST) - blue stimuli

Time Frame

24 months

Title

Change in FST Red

Description

Change in Full-Field Stimulus Testing (FST) - red stimuli

Time Frame

24 months

Title

Change in VFQ-25

Description

Change in Visual Function Questionnaire-25 (VFQ-25) score (adult subjects)

Time Frame

24 months

Title

Change in CVAQ

Description

Change in Cardiff Visual Ability Questionnaire for Children (CVAQC) score (pediatric subjects)

Time Frame

24 months

Title

Change in PLR

Description

Change in Pupillary Light Reflex (PLR) (latency and amplitude)

Time Frame

24 months

Title

Change in NIRAF

Description

Change in Near Infrared AutoFluorescence (NIRAF)

Time Frame

24 months

Title

Change in BCVA in Treated Contralateral Eye

Description

Change in Best Corrected Visual Acuity (BCVA) in Treated Contralateral Eye

Time Frame

24 months

Title

Change in BCVA in Non-Treated Contralateral Eye

Description

Change in Best Corrected Visual Acuity (BCVA) in Non-Treated Contralateral Eye

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

ProQR Medical Monitor

Organizational Affiliation

ProQR Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Scheie Eye Institute, University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Ghent University Hospital and Ghent University

City

Ghent

ZIP/Postal Code

B-9000

Country

Belgium

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://www.proqr.com

Description

Sponsor website

Learn more about this trial

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

We'll reach out to this number within 24 hrs