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

Sponsor

ProQR Therapeutics (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05085964

Collaborator

(none)

Enrollment

Locations

Arm

57.6

Anticipated Duration (Months)

2.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

PQ-421a-002 (Helia) is an open-label, extension study to evaluate the safety, tolerability and efficacy of QR 421a administered via intravitreal (IVT) injection in one or both eyes, in subjects ≥ 18 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.

Condition or Disease	Intervention/Treatment	Phase
Retinitis Pigmentosa Usher Syndrome Type 2	Drug: RNA antisense oligonucleotide for intravitreal injection	Phase 2

Detailed Description

PQ-421a-002 is an open-label, extension study to evaluate the safety, tolerability and efficacy of QR-421a in subjects with RP due to mutations in exon 13 of the USH2A gene.

Subjects that have participated in QR-421a clinical studies, including study PQ-421a-001, 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 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.

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 study eye will be those from the preceding QR-421a study. Baseline functional and structural measurements for the fellow eye will be those from the Screening /Day 1 visit of the current study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

The study consists of two parts: an open-label dosing and/or 1 year follow-upThe study consists of two parts: an open-label dosing and/or 1 year follow-up

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 13, 2021

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: RNA antisense oligonucleotide for intravitreal injection There is only one treatment arm in the PQ-421a-002 study: all subject that can be dosed will receive QR-421a in an open label fashion.	Drug: RNA antisense oligonucleotide for intravitreal injection 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.

Arm

Intervention/Treatment

Other: RNA antisense oligonucleotide for intravitreal injection

There is only one treatment arm in the PQ-421a-002 study: all subject that can be dosed will receive QR-421a in an open label fashion.

Drug: RNA antisense oligonucleotide for intravitreal injection

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.

Outcome Measures

Primary Outcome Measures

Ocular adverse events (AEs) [24 months]
Incidence and severity of ocular adverse events (AEs)
Adverse events (AEs) [24 months]
Incidence and severity of non-ocular adverse events (AEs)

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA) [24 months]
Change from baseline
Low Luminance Visual Acuity (LLVA) [24 months]
Change from baseline
Ellipsoid Zone (EZ) area/width by spectral domain optical coherence tomography (SD-OCT) [24 months]
Change from baseline
Static perimetry [24 months]
Change from baseline
Microperimetry [24 months]
Change from baseline
Exposure of QR-421a in serum [12 months]
Exposure of QR-421a in serum

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Clinical Research Operations, Massachusetts Eye and Ear	Boston	Massachusetts	United States	02114
2	University of Michigan, Kellogg Eye Center	Ann Arbor	Michigan	United States	48105
3	Casey Eye Institute, Oregon Health & Science University	Portland	Oregon	United States	97239
4	Retina Foundation of the Southwest	Dallas	Texas	United States	75231
5	Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre	Montréal		Canada	H4A 3J1
6	Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique	Montpellier		France	34295
7	Centre de maladies rares CHNO des Quinze Vingts	Paris		France	75012