Ultevursen for Vision Impairments

Recruiting at 13 trial locations

Overseen By Kimberly Stepien, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Laboratoires Thea

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Non-exon 13 mutations, Ocular infections, Glaucoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 18 months

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a drug called ultevursen, which is injected into the eye, for patients with a specific genetic form of Retinitis Pigmentosa. The drug targets and modifies the genetic mutation causing their vision loss.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on treatments that affect the immune system or have used investigational drugs recently, you may need to discuss this with the trial team.

What data supports the effectiveness of the treatment Ultevursen for Retinitis Pigmentosa?

Gene therapy has shown promise in treating retinitis pigmentosa, with improvements in vision observed in some patients. Similar treatments, like voretigene neparvovec, have been effective in improving vision in patients with certain genetic mutations, suggesting potential for Ultevursen. ^{1 2 3 4 5}

Research Team

Sepul Bio Medical Monitor

Principal Investigator

Sepul Bio

Sepul Bio Clinical Operations Director

Principal Investigator

Sepul Bio

Eligibility Criteria

This trial is for adults and minors with parental consent who have Retinitis Pigmentosa due to USH2A gene mutations. Participants must have a certain level of vision in both eyes, no treatment history with genetic or stem-cell therapy, and not be allergic to the study medication components.

Inclusion Criteria

I am willing and able to follow the study's requirements and attend all visits.

I have been diagnosed with RP, either with Usher syndrome type 2 or the nonsyndromic form.

I have a genetic condition linked to specific mutations in the USH2A gene.

Exclusion Criteria

I haven't used any experimental drugs or devices recently and don't plan to during the study.

I have never had genetic or stem-cell therapy for any condition.

You are allergic to the injection or any of its ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a loading dose of ultevursen on Day 1, followed by maintenance doses at Month 3 and every 6 months thereafter

18 months

Visits on Day 1, Month 3, and every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Treatment Details

Interventions

• Ultevursen

Trial Overview The trial tests Ultevursen's effectiveness, safety, and tolerability when injected into the eye compared to a sham procedure. It targets patients with specific genetic mutations affecting their vision.

Participant Groups

Group I: Ultevursen 60/60 µg Experimental Treatment 1 Intervention

60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter

Group II: Ultevursen 180/60 µg Experimental Treatment 1 Intervention

180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter

Group III: Sham-procedure Placebo Group 1 Intervention

Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter

Ultevursen is already approved in European Union, United States for the following indications:

Approved in European Union as Ultevursen for:

• Orphan designation for Usher syndromes

Approved in United States as Ultevursen for:

• Currently in Phase 2b clinical trial for Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene

Who Is Running the Clinical Trial?

Laboratoires Thea

Lead Sponsor

Trials

64

Recruited

6,900+

ProQR Therapeutics

Lead Sponsor

Trials

12

Recruited

220+

Sepul Bio

Collaborator

Trials

6

Recruited

130+

Sepul Bio

Industry Sponsor

Trials

7

Recruited

170+

Findings from Research

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

Voretigene neparvovec (Luxturna®) is a gene therapy that delivers a functioning RPE65 gene to retinal cells, showing significant improvements in vision-related mobility tests in patients with RPE65 mutation-associated inherited retinal dystrophy after a single subretinal injection, with effects lasting up to 4 years.

The treatment is generally safe, with most side effects being transient and non-serious, although there was one reported case of retinal detachment; ongoing studies are needed to further assess long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voretigene Neparvovec: A Review in RPE65 Mutation-Associated Inherited Retinal Dystrophy. Kang, C., Scott, LJ.[2021]

In a study of 8 patients treated with the gene therapy voretigene neparvovec (VN), retinal atrophy was observed in all eyes, both within and outside the treated area, over a follow-up period of 6-24 months.

Despite the development of retinal atrophy, the functional vision outcomes remained stable, indicating that VN may provide lasting benefits even in the presence of atrophic changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec. Reichel, FF., Seitz, I., Wozar, F., et al.[2023]

A survey of 55 centers in Europe revealed that by June 2021, 8 out of 26 centers had treated 57 patients with RPE65 biallelic mutation-associated inherited retinal degeneration using voretigene neparvovec (VN), indicating its growing adoption since its approval in 2018.

The main reasons for patients not qualifying for treatment included having too advanced or mild disease, with 50% of centers reporting high patient satisfaction with the treatment outcomes, particularly in quality of life improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Management of Patients with RPE65 Mutation Associated Inherited Retinal Degenerations in Europe: Results of a 2-Year Follow-Up Multinational Survey. Lorenz, B., Tavares, J., van den Born, LI., et al.[2023]

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>G (p.His527Arg) - a case report. Bjeloš, M., Bušić, M., Ćurić, A., et al.[2023]

References

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

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. [2023]

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

Voretigene Neparvovec: A Review in RPE65 Mutation-Associated Inherited Retinal Dystrophy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Current Management of Patients with RPE65 Mutation Associated Inherited Retinal Degenerations in Europe: Results of a 2-Year Follow-Up Multinational Survey. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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