Antisense Oligonucleotide Therapy for Retinal Dystrophy

Age: Any Age

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: n-Lorem Foundation

Must not be taking: Steroids, Amiodarone, Plaquenil, others

Disqualifiers: Ocular infection, Macular edema, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nL-PRPH2-001, an antisense oligonucleotide therapy, for individuals with retinal dystrophy caused by a specific genetic mutation in the PRPH2 gene. The research aims to determine if this treatment can improve eyesight or slow vision loss. Suitable candidates have been diagnosed with retinal dystrophy due to the PRPH2 c.623G>A (p.Gly208Asp) mutation and can travel for regular check-ups. As a Phase 1, Phase 2 trial, the research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in vision care.

Do I need to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial excludes participants who are currently using or have recently used drugs known to be toxic to the eye, such as steroids and some other specific medications. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that certain new treatments, called antisense oligonucleotide (ASO) therapies, are being tested for safety and effectiveness in treating genetic eye conditions like retinal dystrophy. In studies of similar ASO treatments, most participants tolerated the treatment well. Some experienced mild side effects, such as eye irritation or discomfort, but these were not serious.

Since this trial is in the early stages, the main goal is to determine the treatment's safety for people. While the treatment undergoes careful testing, some unknown side effects may still occur. However, ASO therapies are already used for other conditions, suggesting they can be safe when used properly. Participants can feel reassured by the careful monitoring in place during these trials to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for retinal dystrophy, which typically focus on managing symptoms or slowing progression, nL-PRPH2-001 offers a new approach by using antisense oligonucleotide technology. This treatment targets the genetic root of the condition, aiming to correct the faulty gene expression responsible for retinal degeneration. Researchers are excited because this mechanism has the potential to not only halt disease progression but also restore some degree of vision by directly addressing the underlying cause. Such a targeted genetic approach is a promising leap forward compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for Retinal Dystrophy?

Research has shown that antisense oligonucleotide (ASO) therapy could help with genetic conditions like retinal dystrophy, which affects vision. ASOs target and modify the gene mutations causing these conditions. In this trial, participants will receive nL-PRPH2-001, an ASO treatment specifically for individuals with PRPH2-related retinal dystrophy, aiming to correct the faulty genes responsible for vision problems. Early studies suggest that ASO therapy can improve vision by addressing these genetic issues. However, because this treatment is tailored to each person, its effectiveness can vary based on an individual's unique genetic makeup. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Retinal Dystrophy due to a specific PRPH2 mutation. Participants must have certain vision capabilities, agree to contraception if applicable, and be able to travel for study visits. Excluded are those with conditions that may interfere with the study or pose risks, such as high eye pressure, recent eye treatments, or other genetic causes of retinal disease.

Inclusion Criteria

Have a BCVA in the worse eye of at least Count Fingers (CF) or better

Have written informed consent and able to comply with all study requirements

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

Exclusion Criteria

Any condition that in the opinion of the Investigator would ultimately prevent the participant from completion of the study procedures

Intraocular pressure in the eye(s) to be treated is greater than 25 mmHg

Presence of any intravitreal device

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized antisense oligonucleotide (ASO) treatment for Retinal Dystrophy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• nL-PRPH2-001

Trial Overview

The trial involves a personalized antisense oligonucleotide (ASO) drug called nL-PRPH2-001 designed specifically for one participant with Retinal Dystrophy caused by the PRPH2 mutation. The focus is on assessing the safety and effectiveness of this tailored treatment approach.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

n-Lorem Foundation

Lead Sponsor

Trials

5

Recruited

5+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07177196

Study Details | NCT07177196 | Personalized Antisense ...

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

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12470102/

Genotype–Phenotype Correlations in PRPH2 Retinopathies

The autosomal dominant retinitis pigmentosa (adRP) phenotype has been reported to account for 9.6–40% of PRPH2 retinopathy cases [34,35,37,40,48] ...

3.

withpower.com

withpower.com/trial/phase-2-retinal-dystrophies-7-2025-7f00e

Antisense Oligonucleotide Therapy for Retinal Dystrophy

This trial is for individuals with Retinal Dystrophy due to a specific PRPH2 mutation. Participants must have certain vision capabilities, agree to ...

4.

iovs.arvojournals.org

iovs.arvojournals.org/article.aspx?articleid=2793659

Retinal Dystrophies Associated With Peripherin-2 - IOVS

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11469193/

Current and Future Directions in Developing Effective ...

PRPH2 is one of the most commonly mutated inherited retinal disease (IRD) genes, accounting for 3% to 5% of pathogenic variants in several large ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9290825/

PRPH2 mutation update: In silico assessment of 245 reported ...

Mutations in PRPH2, encoding peripherin‐2, are associated with the development of a wide variety of inherited retinal diseases (IRDs).

7.

mdpi.com

mdpi.com/1422-0067/25/5/2913

PRPH2-Related Retinal Dystrophies: Mutational Spectrum ...

We collected genetic data on 220 patients carrying disease-causing variants of PRPH2 from 103 unrelated families with IRD. In addition, we ...

8.

tvst.arvojournals.org

tvst.arvojournals.org/article.aspx?articleid=2802113

A Workshop Report | TVST - ARVO Journals

PRPH2 is one of the most commonly mutated inherited retinal disease (IRD) genes, accounting for 3% to 5% of pathogenic variants in several large-scale IRD ...