Sepofarsen for Leber Congenital Amaurosis

(HYPERION Trial)

Recruiting at 14 trial locations

Overseen By Sepul Bio Patient Advocacy Director

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Laboratoires Thea

Must not be taking: Carbonic anhydrase inhibitors

Disqualifiers: Other IRD mutations, Ocular pathology, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 4

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Sepofarsen, a new treatment for Leber Congenital Amaurosis (LCA), a rare eye condition that can cause severe vision loss. The study evaluates the effectiveness and safety of Sepofarsen, especially for individuals with a specific genetic mutation in the CEP290 gene. Participants will receive treatment in one eye, while the other eye may receive a placebo (inactive substance) or different doses of Sepofarsen. This trial may suit individuals diagnosed with LCA due to the CEP290 mutation and experiencing vision difficulties in both eyes. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on carbonic anhydrase inhibitors, your dose should not have changed in the last 3 months.

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

Research has shown that sepofarsen, a type of medication, generally has a manageable safety profile for treating Leber Congenital Amaurosis (LCA). While some side effects may occur, they are usually not severe. Previous studies confirmed that sepofarsen remains safe and effective for up to 1.5 years after administration.

Participants in earlier trials demonstrated that sepofarsen is well-tolerated, with no serious side effects directly linked to the treatment. Common side effects reported include mild eye discomfort or redness, typical with eye treatments. Overall, the evidence suggests that sepofarsen has a promising safety record, making it a potential option for those considering joining a clinical trial for this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Leber Congenital Amaurosis?

Sepofarsen is unique because it directly targets the underlying genetic cause of Leber Congenital Amaurosis (LCA), a rare inherited eye disorder. Unlike current treatments, which mainly focus on managing symptoms, Sepofarsen works by correcting the specific mutation in the CEP290 gene that causes LCA. This gene-specific approach offers the potential for more effective and longer-lasting improvements in vision. Researchers are excited because Sepofarsen's targeted action could significantly enhance treatment outcomes for patients, providing hope for better vision restoration compared to existing options.

What evidence suggests that Sepofarsen might be an effective treatment for Leber Congenital Amaurosis?

Research has shown that sepofarsen may improve vision for people with Leber Congenital Amaurosis (LCA). In earlier studies, patients who took sepofarsen experienced noticeable vision improvement, with many able to read at least 15 more letters on a standard eye chart. Sepofarsen is a type of RNA therapy, which works by fixing specific genetic issues to help the eyes function better. Early trials found that this treatment generally had manageable side effects. In this trial, participants will receive sepofarsen in varying dosages and combinations across different treatment arms. These findings suggest that sepofarsen could effectively improve vision for those with LCA caused by certain genetic mutations. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Leber Congenital Amaurosis (LCA) Type 10, specifically those with a certain mutation in the CEP290 gene. Participants must have similar vision impairment in both eyes and some detectable retinal structure. They should also have very limited vision, ranging from roughly 20/50 to light perception only.

Inclusion Criteria

My vision is between 20/50 and nearly complete blindness, but I had better vision before.

My vision in both eyes is nearly the same.

My eye exam shows detectable outer nuclear layer in the macula.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Year 1

One eye receives Sepofarsen and the other eye receives placebo. Injections are administered every 6 months.

12 months

2 visits (in-person)

Treatment Year 2

Continuation of treatment with Sepofarsen in both eyes for some subjects, while others continue with placebo in one eye.

12 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sepofarsen

Trial Overview The study tests Sepofarsen's effectiveness and safety against a placebo in treating LCA type 10. It's a double-masked trial, meaning neither participants nor researchers know who receives the real treatment or placebo. Each eye of a participant gets different treatments for comparison.

How Is the Trial Designed?

Group I: Sepofarsen - Treatment Eye - up to Month 12 Active Control 1 Intervention

Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.

Group II: Mixed - Treatment Eye - up to Month 24 Active Control 1 Intervention

Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.

Group III: Continued - Treatment Eye - up to Month 24 Active Control 1 Intervention

Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

Group IV: Mixed - Fellow Eye - Month 12 to Month 24 Active Control 1 Intervention

Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.

Group V: Mixed - Fellow Eye - up to Month 12 Placebo Group 1 Intervention

Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18 Note: up to Month 12 these subjects receive placebo in the Fellow Eye, as all subjects do.

Group VI: Continued - Fellow Eye - up to Month 24 Placebo Group 1 Intervention

Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

Group VII: Placebo - Fellow Eye - up to Month 12 Placebo Group 1 Intervention

Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.

Who Is Running the Clinical Trial?

Laboratoires Thea

Lead Sponsor

Trials

64

Recruited

6,900+

Sepul Bio

Industry Sponsor

Trials

7

Recruited

170+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9117145/

Intravitreal antisense oligonucleotide sepofarsen in Leber ... Intravitreal administration of the antisense oligonucleotide sepofarsen in patients with Leber congenital amaurosis type 10 showed a manageable safety profile, ...

2. proqr.com proqr.com/press-releases/proqr-announces-positive-top-line-results-from-the-phase-12-study-of-sepofarsen-in-lca10-patients

ProQR Announces Positive Top-Line Results from the ... “We reported today that patients receiving sepofarsen had a clinically meaningful improvement in vision, and in some cases the patient's vision improved to a ...

3. nature.com nature.com/articles/s41591-022-01755-w

Intravitreal antisense oligonucleotide sepofarsen in Leber ... In this trial, sepofarsen resulted in a clinically meaningful gain of at least 15 letters in visual acuity (BCVA) on the ETDRS chart, in almost ...

4. euretina.org euretina.org/resource/abstract_2021_safety-and-efficacy-of-sepofarsen-in-the-second-treated-eye-in-the-phase-1b-2-extension-trial-in-leber-congenital-amaurosis-due-to-mutations-in-the-cep290-gene-insight-trial/

Safety and efficacy of sepofarsen in the second treated eye ... Sepofarsen is an intravitreal RNA therapy that showed clinically meaningful improvements following unilateral injection in a Phase 1b/2 trial ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06891443?term=AREA%5BConditionSearch%5D(Long%20qt%20syndrome%2011%20OR%20%22AKAP9%20long%20QT%20syndrome%22%20OR%20%22%20long%20QT%20syndrome%20caused%20by%20mutation%20in%20AKAP9%22%20OR%20%22%20long%20QT%20syndrome%20type%2011%22%20OR%20%22%20LQT11%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=1

NCT06891443 | Study to Evaluate Sepofarsen in Subjects ... The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is to evaluate the efficacy, safety and tolerability of Sepofarsen in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03913143

NCT03913143 | A Study to Evaluate Efficacy, Safety ... The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of ...

7. proqr.com proqr.com/files/2021-05/Russell%202021%20ARVO%20Safety%20and%20efficacy%20of%20sepofarsen%20in%20the%20second%20treated%20eye%20in%20a%20Ph1b-2%20extension%20trial%20in%20LCA10.pdf

Safety and efficacy of sepofarsen in the second treated eye ... LCA, Leber congenital amaurosis. Page 6. -0,8. -0,7. -0,6. -0,5. -0,4. -0,3. -0,2. -0 ... • Available data confirm the manageable safety profile of IVT sepofarsen.

8. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-sepofarsen-for-patients-with-leber-congenital-amaurosis-due-to-a-specific-genetic-mutation/

Study on the Effectiveness and Safety of Sepofarsen ... This clinical trial examines the safety and effectiveness of Sepofarsen, an antisense oligonucleotide, in treating the rare eye condition Leber Congenital ...