Clinical trial NCT05085964: An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
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
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Laboratoires Thea
Sponsor class: INDUSTRY
Collaborators: name: Sepul Bio
First posted: 2021-10-20
Enrollment: 21
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ocular Adverse Events (AEs)
timeFrame: 1 year, 1 month
measure: Non-ocular Adverse Events (AEs)
timeFrame: 1 year, 1 month
Secondary outcomes:
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 24 months
measure: Low Luminance Visual Acuity (LLVA)
timeFrame: 24 months
measure: Ellipsoid Zone (EZ) Area/Width by Spectral Domain Optical Coherence Tomography (SD-OCT)
timeFrame: 24 months
measure: Static Perimetry
timeFrame: 24 months
measure: Microperimetry
timeFrame: 24 months
measure: Exposure of QR-421a in Serum
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Center for Clinical Research Operations, Massachusetts Eye and Ear
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Kellogg Eye Center
state: Michigan
city: Portland
country: United States
facility: Casey Eye Institute, Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Montréal
country: Canada
facility: Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique
city: Paris
country: France
facility: Centre de maladies rares CHNO des Quinze Vingts
Study officials:
affiliation: Sepul Bio
name: Sepul Bio Medical Monitor
role: STUDY_DIRECTOR
References: