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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

Primary Purpose

Leber's Congenital Amaurosis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

QR-110

About this trial

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

Eligibility Criteria

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

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

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

QR-110

Arm Description

Administered every 3 months

Outcomes

Primary Outcome Measures

Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes

Secondary Outcome Measures

Frequency and Severity of Non-ocular Adverse Events

Change in Best-corrected Visual Acuity (BCVA)

Change in Full-field Stimulus Test (FST)

Average Red Light Score

Change in Full-field Stimulus Test (FST)

Average Blue Light Score

Full Information

NCT ID

NCT03140969

First Posted

May 1, 2017

Last Updated

December 12, 2022

Sponsor

ProQR Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT03140969

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

October 16, 2017 (Actual)

Primary Completion Date

October 2, 2019 (Actual)

Study Completion Date

October 2, 2019 (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

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.

6. Conditions and Keywords

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

Leber's Congenital Amaurosis

Keywords

CEP290, p.Cys998X, c.2991+1655A>G, RNA therapy, Antisense oligonucleotide, Leber's congenital amaurosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

QR-110

Arm Type

Experimental

Arm Description

Administered every 3 months

Intervention Type

Drug

Intervention Name(s)

QR-110

Other Intervention Name(s)

Sepofarsen

Intervention Description

RNA antisense oligonucleotide for intravitreal injection

Primary Outcome Measure Information:

Title

Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Frequency and Severity of Non-ocular Adverse Events

Time Frame

1 year

Title

Change in Best-corrected Visual Acuity (BCVA)

Time Frame

1 year

Title

Change in Full-field Stimulus Test (FST)

Description

Average Red Light Score

Time Frame

1 year

Title

Change in Full-field Stimulus Test (FST)

Description

Average Blue Light Score

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

ProQR Study Director

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

Citations:

PubMed Identifier

35379979

Citation

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.

Results Reference

derived

PubMed Identifier

33795869

Citation

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.

Results Reference

derived

PubMed Identifier

31215818

Citation

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.

Results Reference

derived

PubMed Identifier

30559420

Citation

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.

Results Reference

derived

Learn more about this trial

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

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