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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Retinitis Pigmentosa; Usher Syndrome Type 2
• Intervention / Treatment: Drug: RNA antisense oligonucleotide for intravitreal injection

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: QR421a RNA antisense oligonucleotide for intravitreal injection; 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year, 1 month
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.	1 year, 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (BCVA)	Change from baseline	24 months
Low Luminance Visual Acuity (LLVA)	Change from baseline	24 months
Ellipsoid Zone (EZ) Area/Width by Spectral Domain Optical Coherence Tomography (SD-OCT)	Change from baseline	24 months
Static Perimetry	Change from baseline	24 months
Microperimetry	Change from baseline	24 months
Exposure of QR-421a in Serum	Exposure of QR-421a in serum	12 months

Collaborators and Investigators

• Sponsor: Laboratoires Thea
• Collaborators: Sepul Bio
• Investigators: Study Director: Sepul Bio Medical Monitor, Sepul Bio

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): October 18, 2022
• Study Completion (Actual): October 18, 2022

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Retinal Disease; Retinitis Pigmentosa; Eye Disease; Usher Syndrome; Vision Disorders; QR-421a; Exon 13 Mutation; USH2A gene; Night Blindness; Usherin protein; Deaf Blind; Congenital, Familial and Genetic Disorders; PQ-421a-002
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Congenital Abnormalities; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Ear Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Sensation Disorders; Abnormalities, Multiple; Hearing Disorders; Vision Disorders; Deaf-Blind Disorders; Hearing Loss, Sensorineural; Blindness; Hearing Loss; Deafness; Retinitis; Retinitis Pigmentosa; Usher Syndromes
• Other Study ID Numbers: PQ-421a-002; 2021-002070-93 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No