Study to Evaluate the Safety and Efficacy of Tinlarebant in the Treatment of Stargardt Disease in Adolescent Subjects Lesion(s) in Adolescent Subjects With STGD1

Study Overview
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Brief Summary
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The primary objective of this trial is to assesses the efficacy of tinlarebant in slowing the rate of growth of atrophic lesion(s) in adolescent subjects with STGD1

Detailed Description
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Approximately 90 subjects will be enrolled in this study. Subjects will be assigned to study drug (tinlarebant 5 mg/placebo) with treatment period of upto 24 months with 28 days of follow-up.

Official Title
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Phase 3, Multicenter, Randomized, Double-Masked, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Tinlarebant in the Treatment of Stargardt Disease in Adolescent Subjects

Conditions
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Stargardt Disease 1

Intervention / Treatment
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* Drug: Tinlarebant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 12 to 20 years old, inclusive. Subject must have clinically diagnosed STGD1 (Stargardt disease 1) with at least 1 mutation identified in the ABCA4 gene. Subject must have a defined aggregate atrophic lesion size within 3 disc areas (7.62 mm2), as imaged by FAF in the study eye Subjects must have a BCVA of 20/200 or better for the study eye based on ETDRS letter score Subject and their parent(s) or legal guardian are willing to provide their consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Human Research Ethics Committee (HREC)-approved informed consent form (ICF) prior to participating in any study-related procedures. Subject agrees to comply with all protocol requirements. Exclusion Criteria: Any ocular disease other than Stargardt (STGD1) at baseline that, in the opinion of the investigator, would complicate assessment of a treatment effect. History of ocular surgery in the study eye in the last 3 months. Investigational drug use of any kind in the last 3 months or within 5 half-lives of the investigational drug, whichever is shorter. Any prior gene therapy. Vitamin A (retinol) deficiency as defined as a retinol serum level less than 20 mcg/dL (=0.7 μmol/L).

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 3 randomized, double-masked, parallel group, multicenter study to evaluate the efficacy and safety of Tinlarebant 5 mg in the treatment of adolescent subjects with STGD1.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tinlarebant<br>5 mg tablet taken orally once a day | Drug: Tinlarebant<br>* Tinlarebant drug substance is a white to off-white substance and is dispensed as a tablet for oral administration.<br>|
| Placebo Comparator: Placebo<br>Placebo tablets for tinlarebant 5 mg are prepared similarly but use microcrystalline cellulose, NF, in place of the active drug substance and will be identical in size and appearance. | Drug: Placebo<br>* Not active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure change in atrophic lesion size (definitely decreased autofluorescence, DDAF) by fundus autofluorescence (FAF) photography from baseline |  | Baseline thru month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the change in retinal thickness assessed by spectral-domain optical coherence tomography (SD-OCT) from baseline |  | Baseline thru month 24 | 
| To measure the change in retinal morphology assessed by spectral-domain optical coherence tomography (SD-OCT) from baseline |  | Baseline thru month 24 | 
| To measure change in BCVA (Best Corrected Visual Acuity) score measured by the EDTRS method from baseline |  | Baseline thru month 24 | 
| To measure change in plasma concentration of RBP4 levels (μM) from baseline |  | Baseline thru month 24 | 
| The correlation between change in plasma RBP4 level and the rate of lesion size growth (definitely decreased autofluorescence, DDAF) by fundus autofluorescence (FAF) photography from baseline |  | Baseline thru month 24 | 
| To assess the systemic and ocular safety and tolerability of tinlarebant | Frequency, duration, and severity of AEs | Baseline thru month 24 |