Ultevursen for Retinitis Pigmentosa

(LUNA Trial)

Recruiting at 5 trial locations

Overseen By Andrew Bolan

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Laboratoires Thea

Must not be taking: Carbonic anhydrase inhibitors

Disqualifiers: Non-exon 13 mutations, Other retinal diseases, Unstable CME, 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: 4

Duration: 24 months

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this Phase 2b study is to evaluate the safety and tolerability of Ultevursen administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. This is a multicenter Double-masked, Randomized, Sham-controlled study which will enroll 81 subjects.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have unstable cystoid macular edema and have started or changed the dose of certain medications in the last 3 months, you may not be eligible to participate.

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

Gene therapy has shown promise in treating retinitis pigmentosa, a condition that causes severe vision loss. In a study on a similar gene therapy for a related eye condition, patients experienced improvements in their vision, suggesting potential benefits for treatments like Ultevursen. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults and minors with Retinitis Pigmentosa due to USH2A gene mutations, specifically exon 13. Participants must have a certain level of vision in both eyes and similar disease severity between them. They should be able to consent or assent (for minors) to join the study.

Inclusion Criteria

I am over 18 and agree to participate, or I am 8-17 with parental consent.

Both of my eyes have a specific area measured as ≥2.5 mm by a special eye scan.

My vision is at least 20/80 in both eyes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ultevursen or undergo a sham procedure via intravitreal injection on Day 1 and at Months 6, 12, and 18

24 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Ultevursen

Trial Overview The trial tests Ultevursen's safety and effects when injected into the eye compared to no treatment in people with RP. It's a Phase 2b study where participants are randomly assigned to receive either Ultevursen or a sham procedure, without knowing which one they get.

Participant Groups

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

Subjects will receive an intravitreal injection (IVT) of Ultevursen with concentrations of 3.6 mg/mL for initial dose and 1.2 mg/mL for maintenance doses every 6 months thereafter through Month 18 (up to 4 doses).

Group II: Sham Procedure Placebo Group 1 Intervention

Sham-procedure (no experimental drug administered)

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+

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]