Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy

NCT07177196 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 812793
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Retinal Dystrophy due to PRPH2 mutation

Conditions

Retinal Dystrophy

Outcome Measures

Primary Outcomes (8)

• Safety and Tolerability

  Incidence and severity of treatment emergent ocular adverse events (TEAEs) and serious ocular adverse events

  Baseline to 24 months

• Safety and Tolerability

  Incidence and severity of non-ocular TEAEs and Serious non-ocular adverse events

  Baseline to 24 months

• Safety and Tolerability

  Change from baseline to Best Corrected Visual Acuity (BCVA) and Low Luminance Visual Acuity (LLVA) as measured at every visit

  Baseline to 24 months

• Safety and Tolerability

  Change in Slit-lamp biomicroscopy including intraocular pressure (IOP), and dilated indirect ophthalmoscopy

  Baseline to 24 months

• Safety and Tolerability

  Change in full field electroretinograophy (ffERG) results as measured by electrical activity in the retina

  Baseline to 24 months

• Safety and Tolerability

  Incidence of treatment emergent abnormalities in safety labs

  Baseline to 24 months

• Safety and Tolerability

  Incidence of treatment emergent abnormalities in physical exams

  Baseline to 24 months

• Safety and Tolerability

  Incidence of treatment emergent abnormalities in vital signs

  Baseline to 24 months

Secondary Outcomes (6)

• Structure and Function

  Baseline to 24 months

• Structure and Function

  Baseline to 24 months

• Structure and Function

  Baseline to 24 months

• Structure and Function

  Baseline to 24 months

• Structure and Function

  Baseline to 24 months

Study Arms (1)

Open Label

EXPERIMENTAL

Drug: nL-PRPH2-001

Interventions

nL-PRPH2-001 DRUG

Personalized antisense oligonucleotide

Open Label

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a clinical diagnosis of retinal dystrophy as a result of the PRPH2 variant
• Have written informed consent (signed and dated), and able to comply with all study requirements, and any authorization required by local law
• Be able to travel to the study site and adhere to study related follow-up examinations and/or procedures
• Have a molecular diagnosis of a heterozygous PRPH2 variant: c.623G\>A (p.Gl208Asp) based on genetic testing at Screening (a historic genetic testing report from a certified laboratory is acceptable with Sponsor/Investigator approval)
• Have a BCVA in the worse eye of at least Count Fingers (CF) or better
• Have clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as determined by the Investigator
• Be a non-pregnant and non-lactating female, and either surgically sterile (e.g., ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or without hysterectomy, tubal ligation) or post-menopausal (12 months of spontaneous amenorrhea in females \>55 years of age or, in females \< 55 years, have had 12 months of spontaneous amenorrhea without alternative medical cause); male participants and their female partners of childbearing potential must use appropriate contraception methods, or refrain from sexual activity for the duration of the study and for 3 months after the last study treatment; for women of childbearing potential for whom the Investigator considers that the potential benefit outweighs any risk to the unborn fetus, a highly effective method of contraception must be used

You may not qualify if:

• There is any condition that in the opinion of the Investigator, would ultimately prevent the participant from completion of the study procedures
• There is a present (current) active ocular infection (including herpes simplex virus, varicella zoster or cytomegalovirus) in either eye
• There is current cystoid macular edema (CME) in the treatment eye(s); CME is permissible if stable for 3 months in the opinion of the Investigator (with or without treatment); past CME is permissible if resolved for more than 1 month
• There are lens opacities in the eye(s) to be treated that are clinically significant in the opinion of the Investigator or that would prevent clinical and photographic evaluation of the retina
• Receipt within 1 month prior to informed consent of any intraocular or periocular surgery, or IVT injection, or planned/anticipated intraocular surgery or procedure during the course of the study
• Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease
• There is any secondary or alternate genetic cause of retinal disease other than the heterozygous PRPH2 c.623G\>A (p.Gly208Asp) variant
• There has been use of any investigational drug or device within 3 months or 5 half-lives of the first treatment day (Day 1), whichever is longer, or plans to participate in another study of a drug or device during the trial period and for 3 months after the end of the trial period
• There is presence of any significant ocular/non-ocular disease/disorder (including laboratory abnormalities) which, in the opinion of the Investigator, may put the participant at risk, or may influence the results of the trial, or impact the ability of the participant to participate in the trial
• The intraocular pressure in the eye(s) to be treated is greater than 25 mmHg (even in the presence of glaucoma or ocular hypertension which is stabilized on therapy)
• Prior pars plana vitrectomy in the eye(s) to be treated that may affect treatment in the opinion of the Investigator
• Presence of any intravitreal device (e.g., steroid implant)

Sponsors & Collaborators

• n-Lorem Foundation: lead
• University of California, San Diego: collaborator

Study Sites (1)

University of California San Diego

San Diego, California, 92093, United States

Location

MeSH Terms

Conditions

Retinal Dystrophies

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 16, 2025
• Study Start: August 28, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (1)