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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
Sponsored by
ProQR Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  1. 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
  2. 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:

  1. 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.
  2. 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.
  3. 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

First Posted
October 7, 2021
Last Updated
December 12, 2022
Sponsor
ProQR Therapeutics
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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
No
Data Monitoring Committee
No

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
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.
Time Frame
1 year, 1 month
Title
Non-ocular Adverse Events (AEs)
Description
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.
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
No
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
No

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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