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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Retinal Disorder
• Intervention / Treatment: Drug: Placebos; Drug: ZA Low dose; Drug: ZA high dose

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10001
      • NY NY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have read, understood and signed the informed consent form (ICF).
2. Be aged 6 years or older.
3. 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.
4. Be naïve to gene therapy, surgical implantation of prosthetic retinal chips, or subretinal injections.
5. If previously administered ZA , have at least > 3 years since last administration of ZA.
6. Pregnancy testing and contraception before study treatment: Women of childbearing potential must not be pregnant or lactating.

Exclusion Criteria:

1. 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.
2. Have had ocular surgery within 3 months of Screening, including cataract or laser procedures.
3. 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.
4. Have taken any supplements containing ≥ 10,000 IU vitamin A within 60 days of Screening.
5. Have taken any medication that affects bone metabolism within 6 months of Screening.
6. Have circulating 25-hydroxy vitamin D < 20 ng/mL.
7. Use of medications that may interact with a retinoid, including tetracycline, ketoconazole and methotrexate within 60 days of Screening.
8. 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.
9. Have a known and documented allergy to soy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ZA placebo	Drug: Placebos; Placebo
Active Comparator: ZA low dose	Drug: ZA Low dose; ZA low dose
Active Comparator: ZA high dose	Drug: ZA high dose; ZA high dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Retinagenix Holdings

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases
• Other Study ID Numbers: RG201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No