Ultevursen for Retinitis Pigmentosa

(LUNA Trial)

Recruiting at 20 trial locations

Overseen By Sepul Bio Advocacy Director

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Laboratoires Thea

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ultevursen to determine its safety and tolerability for people with Retinitis Pigmentosa (RP), a genetic eye condition affecting vision. Participants will receive either the treatment through an eye injection or a sham procedure (a procedure with no active treatment) for comparison. Suitable candidates have RP linked to specific genetic mutations in the USH2A gene, experience vision loss, and show noticeable vision issues on certain eye tests. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Studies have shown that ultevursen is generally safe and well-tolerated. Research on ultevursen, also known as QR-421a, indicates that a single injection can maintain retinal health and function without major safety issues. In these studies, patients did not experience significant side effects from the treatment. This suggests that ultevursen could be a promising option for those with retinitis pigmentosa caused by changes in the USH2A gene. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ultevursen is unique because it targets retinitis pigmentosa directly with an intravitreal injection. Current treatments, like vitamin A supplements and vision aids, mainly focus on managing symptoms rather than addressing the disease at its source. Ultevursen introduces a new active ingredient delivered directly to the eye, potentially slowing disease progression. Researchers are excited about its potential to offer a more targeted and effective approach than existing options, which could significantly improve patients' quality of life.

What evidence suggests that ultevursen might be an effective treatment for Retinitis Pigmentosa?

Research has shown that ultevursen, which participants in this trial may receive, may help treat Retinitis Pigmentosa (RP) caused by changes in a specific part of the USH2A gene. Earlier studies found that ultevursen can help maintain the eye's structure and function, which is crucial for preserving vision. Data from clinical trials showed positive effects on various aspects of vision, such as sharpness. Importantly, ultevursen was safe and well-tolerated by patients. These findings suggest that ultevursen could be a promising option for people with this specific genetic type of RP. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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

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.

I have been diagnosed with RP, either with Usher syndrome type 2 or without hearing loss.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06627179

Study to Evaluate Ultevursen in Subjects With Retinitis ... The purpose of this Phase 2b study is to evaluate the safety and tolerability of ultevursen administered via intravitreal injection (IVT) in subjects with ...

2. proqr.com proqr.com/press-releases/proqr-announces-positive-results-from-clinical-trial-of-qr-421a-in-usher-syndrome-and-plans-to-start-pivotal-trials

ProQR Announces Positive Results from Clinical Trial of ... QR-421a demonstrated a concordant benefit in multiple measures of vision, including best corrected visual activity (BCVA), static perimetry, ...

3. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2808868

Safety and efficacy of ultevursen for the treatment of USH2A ... Conclusions : Ultevursen was safe and well tolerated. A single injection of ultevursen showed trends toward stabilization of retinal structure and function, ...

4. usher-syndrome.org usher-syndrome.org/file_download/8379d685-ba1f-40b9-a5d6-e7cbaefb6b3a

Positive results of QR-421a Phase 1/2 Clinical Trial for ... “The safety profile and efficacy findings for QR-421a are very encouraging. Usher syndrome and non-syndromic retinitis pigmentosa due to USH2A exon 13.

5. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-phase-23-to-evaluate-safety-and-efficacy-of-421a-in-rp-patients/

A phase 2/3 to evaluate safety and efficacy of 421a in RP ... The study investigated whether the study drug, ultevursen (QR-421a), could slow or stop the worsening of vision loss and whether the study drug is safe. The ...