Cone Rod Dystrophy, Juvenile Macular Degeneration, Stargardt Disease, Stargardt Disease 1
Conditions
Keywords
ABCA4, ABCA4-related retinopathy, Stargardt Disease, Stargardt macular dystrophy, Cone rod dystrophy, Gene editing, RNA, Gene Therapy, Exon editing, IRD, Inherited retinal disease, Inherited retinal dystrophy, Inherited retinal degeneration
Brief summary
This study is an open-label, single ascending dose clinical trial in participants who have ABCA4-related retinopathies. This is the first-in-human clinical trial in which ACDN-01 will be evaluated for safety, tolerability, and preliminary efficacy following a single subretinal injection of ACDN-01.
Detailed description
This is an open-label, single ascending dose study of ACDN-01 in adult participants with ABCA4-related retinopathy. The study is designed to evaluate the safety, tolerability, and evidence of biological effect of SAD levels (low, medium, and high) of ACDN-01 when delivered subretinally. Participants will be followed on study for 2 years for the primary safety and preliminary efficacy endpoints, after which they will continue in the study in a 3-year long-term follow-up period, for a total study duration of 5 years.
Interventions
DRUGACDN-01
ACDN-01 is an AAV-based vector carrying a DNA construct encoding for an ABCA4 RNA exon editor. One time administration is via subretinal injection.
Sponsors
Ascidian Therapeutics, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Presence of mutations in the ABCA4 gene * ABCA4 retinopathy phenotype (Stargardt disease type 1 or cone-rod dystrophy) * Area of atrophy located in the macula of the study eye * BCVA of 20/50 (0.4 logMAR) or worse Key
Exclusion criteria
* The presence of pathogenic or likely pathogenic mutations in other genes known to cause cone-rod dystrophy or Stargardt maculopathy * Retinal disease other than ABCA4-related retinopathy * Presence of a medical condition (systemic or ophthalmic), psychiatric condition, including substance abuse disorder, or physical examination or laboratory finding that may in the opinion of the principal investigator and sponsor preclude adherence to the scheduled study visits, safe participation in the study, or affect the results of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of ACDN-01 as measured by the number and severity of adverse events and serious adverse events. | 12 months | To evaluate the safety and tolerability of a single dose of ACDN-01 when administered to participants with ABCA4-related retinopathy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose for subsequent clinical evaluation will be determined by review of all available safety and tolerability data. | 12 months | To determine maximum tolerated dose (MTD) for subsequent clinical evaluation. |
| To evaluate for evidence of preliminary efficacy based on fundus autofluorescence (FAF). | 24 months | To evaluate for evidence of preliminary efficacy based on change from baseline in the study eye in the area of macular atrophy in mm2 as measured on FAF over 24 months. |
| To evaluate for evidence of preliminary efficacy based on optical coherence tomography (OCT). | 24 months | To evaluate for evidence of preliminary efficacy based on change from baseline in the study eye in change in thickness in retinal layers as measured on OCT, over 24 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess for evidence of preliminary efficacy of ACDN-01 based on best corrected visual acuity. | 24 months | Best Corrected Visual Acuity is measured by number of ETDRS letters read in each eye compared to baseline. |
| To assess for evidence of preliminary efficacy of ACDN-01 based on patient reported outcome measures. | 24 months | Patient-reported outcome measures will be measured by overall and subscale scores on the Michigan Retinal -Degeneration Questionnaire (MRDQ). |
| To assess for evidence of preliminary efficacy of ACDN-01 based on contrast sensitivity. | 24 months | Contrast sensitivity is measured using qCSF tests and will measure number of letters read and change in AUC (area under curve). |
| To assess for evidence of preliminary efficacy of ACDN-01 based on microperimetry. | 24 months | Retinal sensitivity will be measured by change in the location of detectable points. |
Countries
United States
Contacts
Primary ContactAssociate Director, Clinical Operations
Outcome results
None listed