Blindness, Eye Diseases, Eye Diseases, Hereditary, Eye Disorders Congenital, Leber Congenital Amaurosis, Leber Congenital Amaurosis 10, Neurological Manifestations, Retinal Disease, Sensation Disorders, Vision Disorder
Conditions
Keywords
LCA10, p.Cys998X, Antisense oligonucleotides, RNA therapy, QR-110, sepofarsen, CEP290, Leber's Congenital Amaurosis, c.2991+1655A>G
Brief summary
The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is to evaluate the efficacy, safety and tolerability of Sepofarsen in subjects with Leber Congenital Amaurosis (LCA) due to the c.2991+1655A\>G (p.Cys998X) mutation in the CEP290.
Detailed description
This is a double-masked, randomized, placebo-controlled, paired-eye study in which one eye of each subject will serve as a control. At the start of the study the two eyes of each subject will be randomized such that one eye receives sepofarsen and the other eye receives placebo for the first year. In the second year, for all subjects, the eye that was randomized to receive sepofarsen will continue to receive sepofarsen. For the eye that was randomized to placebo in the first year, treatment in the second year will be allocated, as follows: 50% of the eyes will continue to receive placebo, and 50% of the eyes will receive sepofarsen. Sepofarsen and placebo will be administered via intravitreal injection every 6 months.
Interventions
DRUGsepofarsen
RNA antisense oligonucleotide for intravitreal injection
OTHERPlacebo IVT
Placebo with identical appearance to sepofarsen
Sponsors
Laboratoires Thea
Sepul Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Paired-eye design.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A\>G mutation in CEP290. 2. Adults: \>=18 years / Minors: 6 to \<18 years. 3. BCVA (FrACT) equal to or worse than logMAR +0.4 (approximate Snellen equivalent 20/50) to +2.9 logMAR based on quantifiable, reliable FrACT. LP subjects with documented evidence of prior better vision eligible. 4. Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline. 5. Detectable ONL in the macular area as determined by the CRC at Screening.
Exclusion criteria
1. Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes. 2. Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible. 3. Presence of unstable concurrent CME, or subject started on (or changed dose of) topical or systemic carbonic anhydrase inhibitor treatment in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment). 4. Presence of any clinically significant lens opacities/cataracts based on the AREDS lens grading scale. 5. Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Best-Corrected Visual Acuity (BCVA) | 12 Months | Change from baseline in BCVA based on the Freiburg Acuity and Contrast Test (FrACT) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | PGI-C (PATIENT GLOBAL IMPRESSION OF CHANGE ) assesses a patient's perception of overall change in their vision in the respective eye over time. The minimum score (best outcome) is 1 ("Very Much Better") and the maximum score (worst outcome) is 7 ("Very Much Worse"). Higher scores indicate a worse health outcome (greater worsening). |
| Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | — |
| Change from baseline in retinal sensitivity as measured by dark-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | — |
| Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF | Month 12 | — |
| Change from baseline in retinal sensitivity as measured by light-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | — |
| Response in BCVA (FrACT), defined as an improvement of at least 0.2 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response in BCVA (FrACT), defined as an improvement of at least 0.3 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response in Low Luminance Visual Acuity (LLVA) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response in Full-Field Stimulus Test (FST) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response in Patient Global Impression of Change (PGI-C) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response in Contrast Sensitivity (CS) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. | Month 12 | — |
| Response defined as a clinically relevant improvement according to a multimodal assessment in TEs compared to the corresponding response in PCEs at 12 months | Month 12 | The multimodal assessment is based on a combination of visual acuity, retinal sensitivity, CS, functional vision, and/or PRO |
| Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age | Month 12 | — |
| Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age | Month 12 | — |
| Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age | Month 12 | — |
| Change from baseline in eye-specific Patient Global Impression of Severity (PGI-S) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | PGI-S (PATIENT GLOBAL IMPRESSION OF SEVERITY ) assesses a patient's perception of severity of their eye condition in the respective eye over the past week. The minimum score (best outcome) is 1 ("None") and the maximum score (worst outcome) is 5 ("Very Severe"). Higher scores indicate a worse health outcome (greater severity). |
| Change from baseline in Best-Corrected Visual Acuity (BCVA) based on the ETDRS and/or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | — |
| Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) | Month 12 | — |
Countries
Belgium, Brazil, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
CONTACTSepul Bio Patient Advocacy Director
CONTACTSepul Bio Chief Medical Officer
Outcome results
None listed