Antisense Oligonucleotide Treatment for Retinitis Pigmentosa

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Disqualifiers: Allergy to ASO components, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate a specific antisense oligonucleotide medication in one patient with posterior column ataxia with retinitis pigmentosa. The main question it aims to answer is: what is the safety and tolerability of this medication in a single participant.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug nL-FLVC-001 for treating retinitis pigmentosa?

Antisense oligonucleotides (ASOs), like the drug nL-FLVC-001, have shown promise in treating inherited retinal diseases by targeting and modifying specific genetic material to slow disease progression. Similar treatments, such as QR-110, have been effective in restoring normal function in other retinal conditions, suggesting potential effectiveness for nL-FLVC-001 in retinitis pigmentosa. ^{1 2 3 4 5}

Is antisense oligonucleotide treatment generally safe for humans?

Antisense oligonucleotide treatments, like QR-110, have shown promising safety results in studies for other eye conditions, such as Leber congenital amaurosis, where they were well tolerated in animal models and showed no off-target effects. ^{5 6 7 8 9}

How is the drug nL-FLVC-001 unique for treating retinitis pigmentosa?

The drug nL-FLVC-001 is an antisense oligonucleotide treatment, which is a novel approach for retinitis pigmentosa, a condition with limited treatment options. Unlike existing therapies that mainly focus on managing symptoms, this treatment targets the genetic cause of the disease, potentially altering its progression. ^{4 10 11 12 13}

Eligibility Criteria

This trial is for a single patient with posterior column ataxia and retinitis pigmentosa due to FLVCR1 mutation. Specific eligibility criteria are not provided, indicating that the participant has likely been pre-selected.

Inclusion Criteria

I can travel to the study location and follow the study's schedule.

My condition is genetically confirmed to be FLVCR1-related.

Informed consent/assent provided by the participant (when appropriate), and/or participant's parent(s) or legally authorized representative(s)

Exclusion Criteria

Allergy to any of the ASO components

Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

The participant receives an injection of the antisense oligonucleotide nL-FLVC-001 into the vitreous

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• nL-FLVC-001

Trial Overview The trial is testing nL-FLVC-001, an antisense oligonucleotide treatment, on one patient. It focuses on assessing the safety and how well the patient can tolerate this medication.

Participant Groups

Group I: nL-FLVC-001 Arm Experimental Treatment 1 Intervention

nL-FLVC-001 is an antisense oligonucleotide that will be injected into the vitreous

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

Both patients with PRPF31-related retinitis pigmentosa experienced similar clinical courses, with early onset of night blindness and relatively preserved visual acuity into their 30s, but significant deterioration of their visual fields starting in their teens.

Genetic analysis confirmed that mutations in the PRPF31 gene were responsible for their autosomal dominant retinitis pigmentosa, highlighting the importance of genetic testing in understanding the progression of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. Kurata, K., Hosono, K., Hotta, Y.[2018]

A 10-year-old boy with progressive vision loss was diagnosed with RPE65 retinal dystrophy, and genetic testing identified a likely pathogenic mutation (RPE65 c.499G>T) and a variant of uncertain significance (RPE65 c.1580A>G).

The study concludes that the RPE65 c.1580A>G variant should be reclassified as pathogenic, suggesting that patients with this variant could benefit from targeted gene therapy using voretigene neparvovec, which aims to replace the defective RPE65 gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathogenicity reclassification of the RPE65 c.1580A&gt;G (p.His527Arg) - a case report. Bjeloš, M., Bušić, M., Ćurić, A., et al.[2023]

Improvements in functional vision, including ambulatory navigation and light sensitivity, were maintained for 3 to 4 years after voretigene neparvovec (VN) treatment in patients with biallelic RPE65 mutation-associated inherited retinal disease, indicating long-term efficacy.

The safety profile of VN was favorable, with no serious adverse events related to the treatment reported, although one patient experienced retinal detachment, which is consistent with risks associated with the injection procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years. Maguire, AM., Russell, S., Chung, DC., et al.[2021]

References

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

Antisense oligonucleotide therapeutics in clinical trials for the treatment of inherited retinal diseases. [2022]

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

Natural course of retinitis pigmentosa over a three-year interval. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Pathogenicity reclassification of the RPE65 c.1580A&gt;G (p.His527Arg) - a case report. [2023]

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

Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models. [2021]

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

Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years. [2021]

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

Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. [2023]

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

Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290. [2022]

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

Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Assessment of functional vision score and vision-specific quality of life in individuals with retinitis pigmentosa. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosa. [2022]

13. Romania pubmed.ncbi.nlm.nih.gov

[Retinitis pigmentosa--clinical and genetic aspects with low vision]. [2010]