Clinical trial NCT06435000: An Observational Study in Subjects to Follow the Progression of Stargardt Disease Type 1 (STGD1) Caused by Bi-Allelic Autosomal Recessive Mutations in the ABCA4 Gene
Official title: An Observational Study in Subjects to Follow the Progression of Stargardt Disease Type 1 (STGD1) Caused by Bi-Allelic Autosomal Recessive Mutations in the ATP Binding Cassette Subfamily A Member 4 (ABCA4) Gene
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Stargardt
Stargardt's Disease
Stargardt Disease
STGD1
Keywords: POLARIS
Splicebio
STGD1
ABCA4
Lead sponsor: Splice Bio
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 75
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be selected that have a genetic and clinical diagnosis of STGD1 and fulfil all other entry criteria.

Brief summary: This is an Observational Study to Follow the Progression of Stargardt Disease Type 1 (STGD1) Caused by Bi-Allelic Autosomal Recessive Mutations in the ABCA4 Gene

This is a multicenter study which will enroll approximately 75 subjects

Detailed description: Comprehensive knowledge of a disease is essential to the design and conduct of well-controlled, interventional clinical trials. Understanding of the disease state is important for identifying the patient population for a clinical trial, study duration, and selection of clinically meaningful endpoints.

Observational studies play an important role in the understanding of rare diseases and facilitating effective development of potential therapies. To support clinical research, observational studies can help define the clinical features of a rare disease, rate of progression, pathophysiology, and other important factors. Further, following the course of a disease over time allows investigators to identify demographic variables, genotypic and phenotypic features, and other characteristics that may correlate with disease and outcomes in the absence of treatment. Thus, observational studies are useful in guiding the design of therapeutic studies, including selection of the patient population, trial duration, and the types of outcome measures to evaluate efficacy and safety.

Results of a natural history study evaluating the progression of atrophy secondary to Stargardt Disease have been published using retrospective and prospective cohorts of patients (ProgStar, Strauss et al., 2016).

In summary, the current study is a prospective observational study of patients with STGD1, the aim of which is to further enhance understanding of disease progression and structural and functional markers that can be used to evaluate the efficacy and safety of therapeutic interventions, especially in light of advancements in imaging technology.

Eligibility criteria: Inclusion Criteria:

1. Provide written consent
2. Are male or female aged 12-65 years old
3. Have a diagnosis of STGD1 caused by bi-allelic likely pathogenic or pathogenic variants in the ABCA4 gene confirmed genotypically by an accredited genotyping laboratory
4. Have a history of STGD1 progression within the last 2 years, in the opinion of the investigator.
5. Eligible eye(s) must have:

   1. BCVA of between 24-88 ETDRS letters, inclusive (20/20 - 20/320 Snellen equivalent, 0.0-1.2 logMAR) at the Screening Visit.
   2. Clinical evidence of a macular lesion phenotypically consistent with Stargardt Disease.
   3. Fundus autofluorescence (FAF) measurement of definitely decreased autofluorescence (DDAF) as measured by the Central Reading Center (CRC).
   4. Total lesion must be imaged in its entirety.
   5. All total lesion borders must be ≥300 microns from all image edges.
6. Eligible eye(s) must have clear ocular media and adequate pupillary dilation, including no allergy to dilating eyedrops, to permit good quality retinal imaging.

Exclusion Criteria:

1. Are an immediate family member (e.g., child, sibling) of the Sponsor or study site personnel.
2. Have any concurrent ocular disease that would affect study procedures or outcomes (e.g., cataracts; subjects can be enrolled 90 days after successful cataract surgery) in eligible eyes.
3. Have two likely pathogenic or pathogenic variants (not STGD1) in autosomal recessive inherited retinal dystrophy (IRD) genes or a single likely pathogenic or pathogenic variant in autosomal dominant or X-linked IRD genes.
4. Have had any intraocular surgery or thermal laser within 90 days of study entry or any prior thermal laser in the macular region within the eligible eye(s).
5. Have any major surgical procedure within 30 days of the Screening Visit or planned or anticipated major surgery during the study period.
6. Are unwilling to stop taking the following products at Screening and throughout the study:

   1. Supplements containing vitamin A or beta-carotene, liver-based products.
   2. Prescription oral retinoids.
7. Have actively participated in an investigational therapy study or have received any investigational therapy within 90 days of the Screening Visit or 5 half-lives, whichever is longer. Note: any ophthalmic history of gene therapy, stem cell therapy, surgical implantation of prosthetic retinal chips, or intravitreal or sub-retinal injections exclude the subject from study participation.
8. Have known serious allergies to the fluorescein dye that might be used to measure intraocular pressure (IOP), ocular dilating drops, topical ocular anesthetic, or any history of anaphylaxis reaction.
9. Have a history of amblyopia in the eligible eye(s).
10. Have 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 affect the subject's ability to participate in the study.

Primary outcomes:
measure: Document disease progression based on change from baseline in lesion size as measured by DDAF on FAF imaging
timeFrame: 96 weeks
Secondary outcomes:
measure: Change from baseline in ellipsoid zone (EZ) area as measured by SD-OCT
timeFrame: 96 weeks
measure: Change from baseline in BCVA using ETDRS
timeFrame: 96 weeks
measure: Change from baseline in LLVA using ETDRS
timeFrame: 96 weeks
measure: Change from baseline in retinal sensitivity based on macular microperimetry
timeFrame: 96 weeks
measure: Change from baseline in contrast sensitivity scores
timeFrame: 96 weeks
measure: Change from baseline using Patient Reported Outcome Questionnaires
timeFrame: 96 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Shiley Eye Institute
state: California
city: Aurora
country: United States
facility: UCHealth Sue Anschutz-Rodgers Eye Center
state: Colorado
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Wilmer Eye Institute, Johns Hopkins University MD 21287
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Clinical Research Center
state: Michigan
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: Oxford
country: United Kingdom
facility: Oxford Eye Hospital
Study officials:
References: