Tinlarebant for Stargardt Disease

(DRAGON Trial)

Recruiting at 50 trial locations

Overseen By Belitebio - Clinical Trial

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Belite Bio, Inc

Disqualifiers: Ocular disease, Ocular surgery, Gene therapy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

104 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called tinlarebant to see if it can slow down eye damage in teenagers with a condition called STGD1. About 90 participants will take tinlarebant for an extended period. The goal is to see if tinlarebant can help prevent their vision from getting worse.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have used any investigational drugs in the last 3 months, you may not be eligible to participate.

How is the drug Tinlarebant unique for treating Stargardt disease?

Tinlarebant is unique because it aims to reduce the accumulation of vitamin A dimers and lipofuscin, which are substances that build up in the eyes of people with Stargardt disease, potentially slowing the progression of vision loss. Currently, there are no standard treatments that have fully passed clinical trials for this condition. ^{1 2 3 4 5}

Eligibility Criteria

Adolescents aged 12-20 with Stargardt Disease (STGD1) and a specific gene mutation. They must have certain eye health criteria, like a lesion size within limits and vision of 20/200 or better. Participants need to agree to follow the study rules and provide informed consent.

Inclusion Criteria

I have Stargardt disease with a confirmed ABCA4 gene mutation.

Subjects must have a BCVA of 20/200 or better for the study eye based on ETDRS letter score

My eye condition has been confirmed with a specific imaging test.

Exclusion Criteria

Vitamin A (retinol) deficiency as defined as a retinol serum level less than 20 mcg/dL (=0.7 μmol/L)

I have no eye conditions other than Stargardt disease that could affect treatment assessment.

I have received gene therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tinlarebant 5 mg or placebo orally once a day

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Tinlarebant

Trial Overview The trial is testing Tinlarebant's effectiveness in slowing down the growth of lesions in the eyes caused by STGD1 compared to a placebo. The main goal is to see if this drug can help preserve vision in affected adolescents.

Participant Groups

Group I: Tinlarebant Experimental Treatment 1 Intervention

5 mg tablet taken orally once a day

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Belite Bio, Inc

Lead Sponsor

Trials

7

Recruited

730+

Findings from Research

The incidence of Stargardt disease (STGD1) was found to be between 1.67 and 1.95 cases per million per year, with a point prevalence of approximately 1 in 22,000 people in 2018, indicating it is a relatively rare condition.

Late-onset STGD1 (diagnosed at age 45 or older) has increased in recent years, making up 33% of diagnoses from 2014-2018, likely due to improved awareness, but misdiagnosis as age-related macular degeneration was common in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry. Runhart, EH., Dhooge, P., Meester-Smoor, M., et al.[2022]

In a study of 42 patients with childhood-onset Stargardt disease (STGD), it was found that this condition leads to severe visual loss and early retinal changes, with 90% of patients carrying at least one disease-causing variant in the ABCA4 gene.

Patients with childhood-onset STGD were more likely to have two harmful variants in the ABCA4 gene compared to those with adult-onset STGD, suggesting that earlier onset may be linked to more severe genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and molecular characteristics of childhood-onset Stargardt disease. Fujinami, K., Zernant, J., Chana, RK., et al.[2022]

Stargardt disease, caused by mutations in the ABCA4 gene, currently lacks effective treatments that have successfully completed clinical trials.

Research is ongoing in various areas, including drugs to reduce harmful vitamin A dimers, stem cell therapies for retinal regeneration, and gene therapy aimed at delivering a functional ABCA4 gene directly into the eye.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New possibilities in the treatment of Stargardt disease]. Zhorzholadze, NV., Sheremet, NL., Tanas, AS., et al.[2020]

Stargardt disease (STGD) is caused by mutations in the ABCR gene, which is crucial for retinal function and is expressed primarily in rod photoreceptors.

The study identified 19 different mutations in the ABCR gene among STGD families, confirming its role as the causal gene for this autosomal recessive retinal disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Allikmets, R., Singh, N., Sun, H., et al.[2022]

Stargardt disease is a common macular dystrophy that typically begins in childhood or early adolescence, leading to progressive vision loss, with a prevalence of about 1 in 8000 to 10,000 individuals.

Characteristic features of Stargardt disease include a bull's eye pattern on the fundus and specific changes in autofluorescence imaging, with peripapillary sparing observed in most cases, suggesting a potential resilience in that area against the effects of the ABCA4 gene mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt Disease. Tsang, SH., Sharma, T.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical and molecular characteristics of childhood-onset Stargardt disease. [2022]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[New possibilities in the treatment of Stargardt disease]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Stargardt Disease. [2019]