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 (POLARIS)

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

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

Study Overview

• Status: Recruiting
• Conditions: Stargardt Disease; Stargardt's Disease; STGD1; Stargardt

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.

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: SpliceBio; Phone Number: +34 934 02 04 56; Email: clinicaltrials@splice.bio

Study Locations

• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • Universitätsklinikum Bonn, Klinik für Augenheilkunde
    • Principal Investigator: Site 302
  • Tübingen, Germany, 72076
    • Recruiting
    • University Eye Hospital Tübingen
    • Principal Investigator: Site 301
• United Kingdom
  • Leeds, United Kingdom, LS9 7T
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust
    • Principal Investigator: Site 204
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • University of Manchester - The Old St Mary's Hospital
    • Principal Investigator: Site 203
  • Oxford, United Kingdom, OX3 9DU
    • Recruiting
    • Oxford Eye Hospital
    • Contact: OUH under the Eye Research Group Oxford
  • London
    • London, London, United Kingdom, EC1V 2PD
      • Recruiting
      • Moorfields Eye Hospital
      • Principal Investigator: Site 201
• United States
  • California
    • San Diego, California, United States, 92093
      • Recruiting
      • Shiley Eye Institute
      • Principal Investigator: Site 108
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • UCHealth Sue Anschutz-Rodgers Eye Center
      • Principal Investigator: Site 109
  • Florida
    • Gainesville, Florida, United States, 32607
      • Recruiting
      • Vitreo Retinal Associates
      • Principal Investigator: Site 114
    • Miami, Florida, United States, 33136
      • Recruiting
      • Bascom Palmer Eye Institute
      • Principal Investigator: Site 104
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Principal Investigator: Site 107
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Wilmer Eye Institute, Johns Hopkins University MD 21287
      • Principal Investigator: Site 111
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts Eye and Ear Infirmary
      • Contact: Center for Clinical Research
      • Principal Investigator: Site 105
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Recruiting
      • Kellogg Clinical Research Center
      • Principal Investigator: Site 106
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Site 113
    • New York, New York, United States, 10032
      • Recruiting
      • CUIMC/Edward S. Harkness Eye Institute
      • Principal Investigator: Site 112
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Eye Center
      • Principal Investigator: Site 110
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Site 103
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Retina Foundation of the Southwest
      • Principal Investigator: Site 102
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Recruiting
      • University of Wisconsin, Madison
      • Principal Investigator: Site 101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Document disease progression based on change from baseline in lesion size as measured by DDAF on FAF imaging	96 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in ellipsoid zone (EZ) area as measured by SD-OCT	96 weeks
Change from baseline in BCVA using ETDRS	96 weeks
Change from baseline in LLVA using ETDRS	96 weeks
Change from baseline in retinal sensitivity based on macular microperimetry	96 weeks
Change from baseline in contrast sensitivity scores	96 weeks
Change from baseline using Patient Reported Outcome Questionnaires	96 weeks

Collaborators and Investigators

• Sponsor: Splice Bio

Publications and helpful links

Helpful Links

• SpliceBio

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: ABCA4; STGD1; POLARIS; Splicebio
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Stargardt Disease
• Other Study ID Numbers: SB-CS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sponsor will wait until data fully analyzed and published before considering sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No