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

NCT05085964 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: PQ-421a-0022021-002070-93
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Best Corrected Visual Acuity (BCVA)

  24 months

• Low Luminance Visual Acuity (LLVA)

  24 months

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

  24 months

• Static Perimetry

  24 months

• Microperimetry

  24 months

Study Arms (1)

QR421a RNA antisense oligonucleotide for intravitreal injection

OTHER

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

Interventions

RNA antisense oligonucleotide for intravitreal injection DRUG

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.

QR421a RNA antisense oligonucleotide for intravitreal injection

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laboratoires Thea: lead
• Sepul Bio: collaborator

Study Sites (7)

Center for Clinical Research Operations, Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

University of Michigan, Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

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

Montreal, H4A 3J1, Canada

Location

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

Montpellier, 34295, France

Location

Centre de maladies rares CHNO des Quinze Vingts

Paris, 75012, France

Location

MeSH Terms

Conditions

Retinitis Pigmentosa; Usher Syndromes; Night Blindness; Retinal Diseases; Eye Diseases; Vision Disorders; Genetic Diseases, Inborn

Interventions

Intravitreal Injections

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Hearing Loss, Sensorineural; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Blindness; Abnormalities, Multiple; Congenital Abnormalities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Injections, Intraocular; Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Study prematurely terminated due to sponsor decision for reasons unrelated to safety.

Results Point of Contact

• Title: Zuhal Butuner - Chief Medical Officer
• Organization: Sepul Bio

contact@sepulbio.com

(905) 599-7887

Study Officials

• Sepul Bio Medical Monitor

  Sepul Bio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: October 20, 2021
• Study Start: September 16, 2021
• Primary Completion: October 18, 2022
• Study Completion: October 18, 2022
• Last Updated: August 7, 2024
• Results First Posted: December 27, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (1); FR (2)