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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nL-FLVC-001 (an antisense oligonucleotide) for retinitis pigmentosa, a rare eye condition that can cause vision loss. Researchers aim to determine the safety and tolerability of this treatment in a single participant. Ideal candidates have a genetic diagnosis of FLVCR1-related disease and can travel for regular follow-up visits. As an Early Phase 1 trial, participants will be among the first to receive this treatment, contributing to understanding its effects in humans.

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.

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

Research shows that antisense oligonucleotides, such as nL-FLVC-001, offer a new approach to treating retinitis pigmentosa, a condition with limited treatment options. Specific safety information for nL-FLVC-001 is not yet available. This trial is in its early stages, with researchers beginning to assess its safety for humans and potential side effects.

Although direct data for nL-FLVC-001 is unavailable, similar treatments have been studied for related conditions and are generally designed to be safe with minimal severe side effects. As with any new treatment, doctors and researchers will closely monitor participants to ensure their safety during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for retinitis pigmentosa, which often focus on managing symptoms or slowing progression, nL-FLVC-001 is an antisense oligonucleotide that targets the genetic root of the disease. This treatment is injected directly into the vitreous of the eye, allowing it to interfere with and modify the faulty genetic instructions that cause the condition. Researchers are excited because this approach could potentially halt or even reverse the deterioration of vision, offering hope for more effective long-term outcomes.

What evidence suggests that this treatment might be an effective treatment for retinitis pigmentosa?

Research has shown that treatments like nL-FLVC-001, which participants in this trial will receive, use antisense oligonucleotides and may help with conditions like retinitis pigmentosa. Other studies have found that similar treatments can greatly slow the loss of photoreceptors, which are crucial for vision. For example, one study reported more than a 50% decrease in photoreceptor loss over two years. This type of treatment has also been linked to better vision, such as improved mobility and increased light sensitivity. Although nL-FLVC-001 remains in the early stages of testing, these findings suggest it could potentially help with vision problems related to retinitis pigmentosa. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. nacuity.com nacuity.com/?page_id=624

Nacuity Pharmaceuticals Announces Positive Data from ... NPI-001 shows more than 50% reduction in photoreceptor loss caused by RP associated with USH over two years. NPI-001 was well tolerated, ...

2. withpower.com withpower.com/trial/early-phase-1-retinitis-7-2023-d5c68

Antisense Oligonucleotide Treatment for Retinitis Pigmentosa Improvements in functional vision, including ambulatory navigation and light sensitivity, were maintained for 3 to 4 years after voretigene neparvovec (VN) ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0098299725000809

Antisense oligonucleotides for inherited retinal diseases Chen et al. A phase 1 first in human study of VP-001; a peptide conjugate of oligonucleotide designed to treat retinitis pigmentosa type 11 patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04864496?term=AREA%5BConditionSearch%5D(%22Retinitis%20Pigmentosa%22)%20AND%20AREA%5BInterventionSearch%5D(%22Acetylcysteine%22)&rank=2

Effects of Treatment With N- Acetylcysteine on Visual ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12022754/

The N=1 Collaborative: advancing customized nucleic acid ... The N=1 Collaborative (N1C) was established to unite academia, industry, patients, and regulators, building an open, shared ecosystem for personalized ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05537220

Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack) NAC Attack is a phase III, multicenter, randomized, placebo controlled trial that will determine if oral NAC provides benefit and is safe in patients with RP.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11387776/

Interim safety and efficacy of gene therapy for RLBP1 ... Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene ...