Retinitis Pigmentosa, Usher Syndrome Type 2
Conditions
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
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.
Interventions
DRUGRNA 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.
Sponsors
Sepul Bio
Laboratoires Thea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Adverse Events (AEs) | 1 year, 1 month | 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) | 1 year, 1 month | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Best Corrected Visual Acuity (BCVA) | 24 months | Change from baseline |
| Exposure of QR-421a in Serum | 12 months | Exposure of QR-421a in serum |
| Microperimetry | 24 months | Change from baseline |
| Low Luminance Visual Acuity (LLVA) | 24 months | Change from baseline |
Countries
Canada, France, United States
Participant flow
Recruitment details
In total 21 participants were enrolled: 19 participants were enrolled after they completed the previous PQ-421a-001 (Stellar) study and 2 participants were enrolled after premature termination of the PQ-421a-004 (Celeste) study.
Participants by arm
| Arm | Count |
|---|---|
| Ultevursen 180ug/60ug 180ug loading dose of QR-421a will be first administered to the contralateral (fellow) eye (as defined in the preceding study), and 60ug will be repeated every 6 months. | 21 |
| Ultevursen 60ug/60ug 60ug loading dose of QR-421a will be first administered to the contralateral (fellow) eye (as defined in the preceding study), and 60ug will be repeated every 6 months. | 0 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Premature termination of study | 21 | 0 |
Baseline characteristics
| Characteristic | Total | Ultevursen 180ug/60ug | Ultevursen 60ug/60ug |
|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 13.5 | 47.7 years STANDARD_DEVIATION 13.5 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 16 Participants | 0 Participants |
| Region of Enrollment Canada | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment France | 8 Participants | 8 Participants | 0 Participants |
| Region of Enrollment United States | 11 Participants | 11 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | — |
| Sex: Female, Male Male | 11 Participants | 11 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 0 |
| other Total, other adverse events | 11 / 21 | 0 / 0 |
| serious Total, serious adverse events | 0 / 21 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 1 year, 1 month
Population: All participants who were enrolled and received at least 1 dose of ultevursen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ultevursen 180ug/60ug | Non-ocular Adverse Events (AEs) | 11 Participants |
| Ultevursen 60ug/60ug | Non-ocular Adverse Events (AEs) | 0 Participants |
Primary
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.
Time frame: 1 year, 1 month
Population: All participants who were enrolled and received at least 1 dose of ultevursen.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ultevursen 180ug/60ug | Ocular Adverse Events (AEs) | Contralateral Eye (CE) - TEAEs | 11 Participants |
| Ultevursen 180ug/60ug | Ocular Adverse Events (AEs) | No TEAEs reported | 10 Participants |
| Ultevursen 60ug/60ug | Ocular Adverse Events (AEs) | Contralateral Eye (CE) - TEAEs | 0 Participants |
Secondary
Best Corrected Visual Acuity (BCVA)
Change from baseline
Time frame: 24 months
Secondary
Ellipsoid Zone (EZ) Area/Width by Spectral Domain Optical Coherence Tomography (SD-OCT)
Change from baseline
Time frame: 24 months
Secondary
Exposure of QR-421a in Serum
Exposure of QR-421a in serum
Time frame: 12 months
Secondary
Low Luminance Visual Acuity (LLVA)
Change from baseline
Time frame: 24 months
Secondary
Microperimetry
Change from baseline
Time frame: 24 months
Secondary
Static Perimetry
Change from baseline
Time frame: 24 months