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An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (HELIA)

Primary Purpose

Retinitis Pigmentosa, Usher Syndrome Type 2

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

RNA antisense oligonucleotide for intravitreal injection

About this trial

This is an interventional treatment trial for Retinitis Pigmentosa focused on measuring QR-421a, Retinitis Pigmentosa, Usher Syndrome, Exon 13 Mutation, USH2A gene, Night Blindness, Usherin protein, Deaf Blind, Retinal Disease, Eye Disease, Vision Disorders, Congenital, Familial and Genetic Disorders, PQ-421a-002

Eligibility Criteria

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

Principal Inclusion Criteria:

Subjects who have participated in a preceding QR-421a study and who may derive benefit from continued treatment with QR 421a, and/or continued follow up, as assessed by the Investigator, in consultation and agreement with the Medical Monitor
An adult (≥ 18 years) willing and able to provide informed consent for participation prior to performing any study related procedures, and suitable verbal, auditory, written and/or tactile sign language communication as to allow informed consent to be obtained, in the opinion of the Investigator.

OR A minor (12 to < 18 years) able to provide age-appropriate assent for study participation, and 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.

Principal Exclusion Criteria:

Presence of any significant ocular or non-ocular disease/disorder (or medication and/or laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study. This includes but is not limited to a subject who has uncontrolled cystoid macular edema (CME) in the treatment eye. CME is permissible if stable for 3 months (with or without treatment). Past CME is permissible if resolved for more than 1 month.
Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the study.
Safety issue during preceding QR-421a study that may compromise subject safety when continued dosing, as determined by the Investigator, and in consultation with the Medical Monitor.

Sites / Locations

Center for Clinical Research Operations, Massachusetts Eye and Ear
University of Michigan, Kellogg Eye Center
Casey Eye Institute, Oregon Health & Science University
Retina Foundation of the Southwest
Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre
Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique
Centre de maladies rares CHNO des Quinze Vingts

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

QR421a RNA antisense oligonucleotide for intravitreal injection

Arm Description

There is only one treatment arm in the PQ-421a-002 study; All participants that are eligible to be dosed will receive QR-421a in an open label fashion.

Outcomes

Primary Outcome Measures

Ocular Adverse Events (AEs)

Number of subjects with ocular treatment emergent adverse events (TEAEs) in the contralateral eye (CE) is presented. Frequency of individual TEAEs by system organ class and preferred term is presented in the safety section and clinical trial summary report. Time frame of reporting is the maximum followup period from first subject first visit to last end of study visit.

Non-ocular Adverse Events (AEs)

Number of subjects with non-ocular treatment emergent adverse events (TEAEs) is presented. Frequency of individual TEAEs by system organ class and preferred term is presented in the safety section and clinical trial summary report. Time frame of reporting is the maximum follow up period from first subject first visit to last end of study visit.

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA)

Change from baseline

Low Luminance Visual Acuity (LLVA)

Change from baseline

Ellipsoid Zone (EZ) Area/Width by Spectral Domain Optical Coherence Tomography (SD-OCT)

Change from baseline

Static Perimetry

Change from baseline

Microperimetry

Change from baseline

Exposure of QR-421a in Serum

Exposure of QR-421a in serum

Full Information

NCT ID

NCT05085964

First Posted

October 7, 2021

Last Updated

December 12, 2022

Sponsor

ProQR Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05085964

Brief Title

An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa

Acronym

HELIA

Official Title

An Open-Label Extension Study to Evaluate the Safety and Tolerability of QR 421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene (Helia)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Terminated

Why Stopped

The sponsor decided to terminate the study early

Study Start Date

September 16, 2021 (Actual)

Primary Completion Date

October 18, 2022 (Actual)

Study Completion Date

October 18, 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

5. Study Description

Brief Summary

PQ-421a-002 (Helia) is an open-label, extension study to evaluate the safety, tolerability and efficacy of QR 421a (ultevursen) administered via intravitreal (IVT) injection in one or both eyes, in subjects ≥ 12 years of age with RP due to mutations in exon 13 of the USH2A gene, for an anticipated period of 24 months, or until provision of continued treatment by other means is available, provided the subject's benefit-risk determination remains positive.

Detailed Description

PQ-421a-002 is an open-label, extension study to evaluate the safety, tolerability and efficacy of QR-421a (ultevursen) in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects that have participated in QR-421a clinical studies, i.e. PQ-421a-001 (Stellar), PQ-421a-003 (Sirius) and PQ-421a-004 (Celeste), will be given the opportunity to enroll into this extension study for continued dosing, provided the subject's benefit-risk assessment is positive, or for additional follow up. The Investigator, in consultation and agreement with the Medical Monitor, will decide on subject's enrollment upon assessment of subject's benefit-risk. QR-421a will be first administered to the Contralateral Eye (CE or fellow eye), as defined in the preceding study, and will be repeated every 6 months. Administration of QR-421a to the Treatment Eye (TE or study eye), as defined in the preceding study, can commence 3 months (9 months for subjects from study PQ-421a-001) after the treatment of the contralateral eye has been initiated and will be repeated every 6 months as well. The Investigator, in consultation and agreement with the Medical Monitor, will decide on dosing of both eyes. Continued subject treatment in this study will be pursued provided that the benefit-risk balance is positive for the individual subject, as discussed and agreed upon with the Medical Monitor. The same safety monitoring protocol and efficacy assessments will apply to both eyes. Baseline functional and structural measurements for the treatment eye will be those from the preceding QR-421a study. Baseline functional and structural measurements for the contralateral eye will be those from the Screening /Day 1 visit of the current study.

6. Conditions and Keywords

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

Retinitis Pigmentosa, Usher Syndrome Type 2

Keywords

QR-421a, Retinitis Pigmentosa, Usher Syndrome, Exon 13 Mutation, USH2A gene, Night Blindness, Usherin protein, Deaf Blind, Retinal Disease, Eye Disease, Vision Disorders, Congenital, Familial and Genetic Disorders, PQ-421a-002

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Eligible participants from previous QR-421a study can be enrolled into this extension study to receive continuous dosing of QR-421a for 24 months or until treatment becomes available (whichever is longer). Subject who receive follow up only, will be in this study for 12 months.

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

QR421a RNA antisense oligonucleotide for intravitreal injection

Arm Type

Other

Arm Description

There is only one treatment arm in the PQ-421a-002 study; All participants that are eligible to be dosed will receive QR-421a in an open label fashion.

Intervention Type

Drug

Intervention Name(s)

RNA antisense oligonucleotide for intravitreal injection

Intervention Description

QR-421a will be first administered to the fellow eye (as defined in the preceding study), and will be repeated every 6 months. Treatment of the study eye (as defined in the preceding study) can commence 3 months (9 months for subjects from study PQ-421a-001) after the treatment of the fellow eye has been initiated and will be repeated every 6 months as well. Continued subject treatment in this study will be pursued provided that the benefit-risk balance is positive for the individual subject.

Primary Outcome Measure Information:

Title

Ocular Adverse Events (AEs)

Description

Time Frame

1 year, 1 month

Title

Non-ocular Adverse Events (AEs)

Description

Time Frame

1 year, 1 month

Secondary Outcome Measure Information:

Title

Best Corrected Visual Acuity (BCVA)

Description

Change from baseline

Time Frame

24 months

Title

Low Luminance Visual Acuity (LLVA)

Description

Change from baseline

Time Frame

24 months

Title

Ellipsoid Zone (EZ) Area/Width by Spectral Domain Optical Coherence Tomography (SD-OCT)

Description

Change from baseline

Time Frame

24 months

Title

Static Perimetry

Description

Change from baseline

Time Frame

24 months

Title

Microperimetry

Description

Change from baseline

Time Frame

24 months

Title

Exposure of QR-421a in Serum

Description

Exposure of QR-421a in serum

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Principal Inclusion Criteria: Subjects who have participated in a preceding QR-421a study and who may derive benefit from continued treatment with QR 421a, and/or continued follow up, as assessed by the Investigator, in consultation and agreement with the Medical Monitor An adult (≥ 18 years) willing and able to provide informed consent for participation prior to performing any study related procedures, and suitable verbal, auditory, written and/or tactile sign language communication as to allow informed consent to be obtained, in the opinion of the Investigator. OR A minor (12 to < 18 years) able to provide age-appropriate assent for study participation, and 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. Principal Exclusion Criteria: Presence of any significant ocular or non-ocular disease/disorder (or medication and/or laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study. This includes but is not limited to a subject who has uncontrolled cystoid macular edema (CME) in the treatment eye. CME is permissible if stable for 3 months (with or without treatment). Past CME is permissible if resolved for more than 1 month. Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the study. Safety issue during preceding QR-421a study that may compromise subject safety when continued dosing, as determined by the Investigator, and in consultation with the Medical Monitor.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

ProQR Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

Center for Clinical Research Operations, Massachusetts Eye and Ear

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

University of Michigan, Kellogg Eye Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48105

Country

United States

Facility Name

Casey Eye Institute, Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Retina Foundation of the Southwest

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre

City

Montréal

ZIP/Postal Code

H4A 3J1

Country

Canada

Facility Name

Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

Centre de maladies rares CHNO des Quinze Vingts

City

Paris

ZIP/Postal Code

75012

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa

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