This is a Dose-finding Study Followed by 2-year Extension Study to Evaluate Safety and Tolerability of Tinlarebant in Adolescent Subjects With Stargardt Disease

Study Overview
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Brief Summary
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Stargardt disease 1 (STGD1) is the most prevalent form of juvenile macular degeneration. It is caused by a rare, inherited autosomal recessive trait, leading to severe and irreversible blindness by the first or second decade of life. Earlier onset of the disease is related to a rapid vision loss, while patients with a later onset tend to have a better prognosis. This study will enrol subjects aged 12-18 years old with a confirmed clinical diagnosis of Stargardt disease type 1 (STGD1). This study will include 2 phases, the phase 1b portion is to determine the optimal dose for phase 2 based on the extent of retinol binding protein 4 (RBP4) reduction after 2 cycles of tinlarebant treatment. The phase 2 portion will evaluate the safety and efficacy of a single daily dose of tinlarebant over a 24-month treatment period.

Official Title
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Phase 1/2, Open-Label, Dose-Finding Followed by 2-Year Extension Study to Evaluate Safety and Tolerability of Tinlarebant in Adolescent Subjects With Stargardt Disease

Conditions
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Stargardt Disease

Intervention / Treatment
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* Drug: tinlarebant


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Subject must have clinically diagnosed Stargardt disease with at least one mutation identified in the ABCA4 gene. Major Exclusion Criteria: Any ocular disease other than Stargardt disease at baseline that, in the opinion of the PI, would complicate assessment of a treatment effect.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tinlarebant<br>Daily, oral administration of one tinlarebant. | Drug: tinlarebant<br>* Phase 1b Portion: tinlarebant will be self-administered orally once daily for 2 cycles, 14 days per cycle. Phase 2 portion: tinlarebant will be self-administered orally once daily for 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate systemic and ocular safety and tolerability of tinlarebant. | To evaluate safety and tolerability of daily dosing of tinlarebant assessed by incidence and/or severity of ocular and non-ocular adverse events. | From baseline to 24 months | 
| The optimal dose for Phase 2. | To determine optimal dose of tinlarebant administered orally in adolescent patients with Stargardt Disease. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in atrophic lesion size. |  | From baseline to 24 months. | 
| Maximum Plasma Concentration (Cmax) of tinlarebant in plasma. |  | Up to 24 months | 
| Time to Maximum Plasma Concentration (Tmax) of tinlarebant in plasma. |  | Up to 24 months | 
| Half-life (t1/2) of tinlarebant in plasma. |  | Up to 24 months | 
| Time to minimal plasma RBP4 level (Tmin) |  | Up to 24 months | 
| Minimum concentration of RBP4 (Cmin) |  | Up to 24 months |