Safety and Efficacy of Zuretinol Acetate in Subjects With Inherited Retinal Disease

Study Overview
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Brief Summary
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To evaluate the efficacy of ZA oral solution in subjects with IRD caused by biallelic recessive RPE65 or LRAT gene mutations and phenotypically diagnosed as Leber's Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP).

Official Title
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Safety and Efficacy of Zuretinol Acetate Oral Solution in Subjects With Inherited Retinal Disease Caused by Mutations in Retinal Pigment Epithelium Protein 65 or Lecithin:Retinol Acyltransferase

Conditions
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Retinal Disorder

Intervention / Treatment
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* Drug: Placebos
* Drug: ZA Low dose
* Drug: ZA high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have read, understood and signed the informed consent form (ICF). Be aged 6 years or older. Have a diagnosis of IRD phenotypically diagnosed as LCA or RP by an ocular geneticist or ophthalmologist and caused by pathologic biallelic autosomal recessive mutation in RPE65 or LRAT as determined by a fully accredited certified central genotyping laboratory. Be naïve to gene therapy, surgical implantation of prosthetic retinal chips, or subretinal injections. If previously administered ZA , have at least > 3 years since last administration of ZA. Pregnancy testing and contraception before study treatment: Women of childbearing potential must not be pregnant or lactating. Exclusion Criteria: Have a presence of concurrent ocular disease that in the opinion of the Investigator would put the subject at greater risk during the study or significantly affect study results. Have had ocular surgery within 3 months of Screening, including cataract or laser procedures. Have taken any prescription or investigational oral retinoid medication (e.g., isotretinoin or acitretin) within 6 months of Screening; subjects who did not tolerate their previous oral retinoid medication will be excluded regardless of the time of last exposure. Have taken any supplements containing ≥ 10,000 IU vitamin A within 60 days of Screening. Have taken any medication that affects bone metabolism within 6 months of Screening. Have circulating 25-hydroxy vitamin D < 20 ng/mL. Use of medications that may interact with a retinoid, including tetracycline, ketoconazole and methotrexate within 60 days of Screening. Use of intraocular or periocular corticosteroids within 90 days of Screening; use of corticosteroid implants within 3 years of Screening; use of systemic corticosteroids unless these are at a steady low dose with low dose level in effect prior to or at Screening; or use of intraocular or periocular anti-vascular endothelial growth factor agents within 2 months of Screening. Have a known and documented allergy to soy.

Ages Eligible for Study
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Minimum Age: 6 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: ZA placebo<br> | Drug: Placebos<br>* Placebo<br>|
| Active Comparator: ZA low dose<br> | Drug: ZA Low dose<br>* ZA low dose<br>|
| Active Comparator: ZA high dose<br> | Drug: ZA high dose<br>* ZA high dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional vision at Week 12 using a visual navigation course at different ambient illumination levels | The primary efficacy endpoint (PEE) will be a measure of functional vision assessed at Week 12 employing mobility testing (Ora Inc, Andover, MA) via their Visual Navigation Challenge (VNC) course. The VNC measures functional vision by evaluating the subject's ability to navigate a maze accurately and successfully at different levels of ambient illumination. The PEE is a comparison between groups in their mean change from randomization to week 12, that is, the difference in VNC score from baseline performance to week 12 performance. Performance on the VNC is assessed using each eye individually and both eyes together at 1 or more levels of illumination that range from 0.35 lux to 500 lux. A subject's VNC score is the lowest level of luminance at which the subject can navigate and correctly pass through the maze. | week 12 |