Subretinal Injection for Leber Congenital Amaurosis

Not currently recruiting at 1 trial location

Overseen By Michael DeSordi, BS, MBA

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Atsena Therapeutics Inc.

Must not be taking: Anticoagulants, Immunosuppressants, Antivirals, others

Disqualifiers: HIV, Glaucoma, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called ATSN-101 (also known as SAR439483) for individuals with Leber Congenital Amaurosis (LCA), an eye disorder causing severe vision loss. Researchers aim to determine if this treatment is safe and improves vision in patients with a specific genetic type of LCA. The treatment involves a subretinal injection, meaning it is injected into the back part of the eye. Suitable candidates for this trial have been diagnosed with LCA due to specific genetic mutations and have significant vision issues in one eye. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial requires that you stop using anticoagulation therapy at least two weeks before surgery and avoid immunosuppressive medications. If you are on any investigational or anti-viral therapies, you may need to stop them depending on their elimination half-life. Please discuss your specific medications with the trial team.

Is there any evidence suggesting that ATSN-101 is likely to be safe for humans?

Initial findings suggest that ATSN-101 has been well-tolerated in previous studies. Research has shown that 12 months after treatment, patients experienced noticeable improvements in vision without any serious side effects. This experimental gene therapy uses a method called subretinal injection, placing the treatment directly behind the retina to target Leber Congenital Amaurosis (LCA). In studies conducted so far, no major safety concerns have emerged, making ATSN-101 promising for those considering joining the trial. ^{1 2 3 4 5}

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

Most treatments for Leber Congenital Amaurosis, a rare genetic eye disorder, focus on gene therapy targeting specific mutations or supportive therapies like visual aids. But the treatment SAR439483 is unique because it involves a subretinal injection, which delivers the therapy directly to the retina where it can have the most impact. Researchers are particularly excited about this method because it allows for precise targeting of the affected area, potentially leading to better outcomes. Additionally, SAR439483 may address a broader range of genetic mutations compared to existing treatments, offering hope to more patients with this condition.

What evidence suggests that ATSN-101 might be an effective treatment for Leber Congenital Amaurosis?

Research has shown that ATSN-101, which participants in this trial may receive, may help treat Leber Congenital Amaurosis (LCA) caused by GUCY2D mutations. In earlier studies, patients who received ATSN-101 experienced significant improvements in their vision after 12 months, especially with higher doses. This gene therapy is administered directly to the eye to correct the faulty genes that cause vision loss. Early results suggest that ATSN-101 is safe and effective in improving eyesight for people with this rare genetic condition. No serious side effects have been reported so far, making it a hopeful option for those affected by LCA. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults and children with Leber Congenital Amaurosis (LCA) due to specific GUCY2D gene mutations. Adults must have very limited vision, while kids can have slightly better sight. Participants need some retinal structure visible on scans and agree to contraception and not donating biological materials post-treatment.

Inclusion Criteria

I have Leber congenital amaurosis due to GUCY2D gene mutations.

My tests show mutations in the GUCY2D gene from a certified lab.

I agree to follow the trial's birth control requirements.

Exclusion Criteria

I am not using, nor plan to use, any anti-viral therapy that could affect the trial treatment.

My eyes are healthy enough for surgery and won't affect the study's outcome.

I haven't had any eye procedures in the last 6 months that would affect my surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive a single subretinal injection of ATSN-101 during the dose escalation or expansion phase

1 day

1 visit (in-person)

Observation

Participants are observed for safety and efficacy of the treatment

52 weeks

Safety Follow-up

Participants are monitored for safety after the observation period

52 weeks

Long-term Follow-up (optional)

Participants may opt into a separate long-term follow-up study

208 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SAR439483

Trial Overview The study tests different doses of SAR439483, injected under the retina, for safety and effectiveness in LCA patients with GUCY2D mutations. It includes a single injection followed by monitoring. Other medications like steroids may be used to manage side effects or prepare the eye.

How Is the Trial Designed?

Group I: ATSN-101 Experimental Treatment 6 Interventions

ATSN-101 single dose according to an ascending dose design (dose escalation phase) or ATSN-101 single dose (dose expansion phase)

Who Is Running the Clinical Trial?

Atsena Therapeutics Inc.

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

Subretinal gene therapy using the AAV2-CB(SB)-hRPE65 vector in RPE65-deficient rd12 mice showed improved retinal function, with significant increases in b-wave amplitudes and faster photoresponse kinetics at certain doses, indicating therapeutic efficacy.

The study established a full-field electroretinogram (ERG) assay to measure the biological activity of the gene therapy vector, which could be useful for evaluating future clinical trials in humans with RPE65-related retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroretinographic analyses of Rpe65-mutant rd12 mice: developing an in vivo bioassay for human gene therapy trials of Leber congenital amaurosis. Roman, AJ., Boye, SL., Aleman, TS., et al.[2021]

In a study using large animal models, sequential bilateral injections of rAAV2-hRPE65v2 were found to be safe and effective for treating Leber's congenital amaurosis (LCA), even when the second eye was treated after the first injection.

Despite the development of neutralizing antibodies against the AAV2 capsid, the treatment did not trigger significant immune responses, and it resulted in improved visual function with minimal inflammation in affected animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. Amado, D., Mingozzi, F., Hui, D., et al.[2022]

Subretinal gene therapy using rAAV2 carrying the RPE65 gene was found to be safe, with no systemic toxicity and only minor ocular adverse events related to the surgical procedure in a study of 15 patients aged 11 to 30.

Visual function improved in all treated patients, particularly in those with the lowest initial acuities, indicating that gene therapy can be effective for restoring vision in specific areas of the retina, although treatment of the fovea may carry risks without benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Jacobson, SG., Cideciyan, AV., Ratnakaram, R., et al.[2022]

Citations

1. atsenatx.com atsenatx.com/press-release/atsena-therapeutics-announces-12-month-safety-and-efficacy-data-from-phase-i-ii-clinical-trial-of-atsn-101-in-lca1-published-in-the-lancet/

Atsena Therapeutics Announces 12-Month Safety and ... Atsena Therapeutics Announces 12-Month Safety and Efficacy Data from Phase I/II Clinical Trial of ATSN-101 in LCA1 Published in The Lancet.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39244273/

Safety and efficacy of ATSN-101 in patients with Leber ... The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

3. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01447-8/fulltext

Safety and efficacy of ATSN-101 in patients with Leber ... The current study is a first-in-human phase 1/2 trial of a gene therapy for Leber congenital amaurosis caused by biallelic mutations in GUCY2D, ...

4. atsenatx.com atsenatx.com/press-release/atsena-therapeutics-announces-positive-12-month-safety-and-efficacy-data-from-ongoing-phase-i-ii-clinical-trial-of-atsn-101-in-patients-with-leber-congenital-amaurosis-caused-by-biallelic-mutations-in/

Atsena Therapeutics Announces Positive 12-month Safety ... At 12 months post-treatment, ATSN-101 has conferred clinically meaningful improvements in vision at the highest dose with no serious treatment-emergent adverse ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03920007

NCT03920007 | Study of Subretinally Injected ATSN-101 ... To evaluate the safety and tolerability of ascending doses of ATSN-101 administered as a unilateral subretinal injection in patients with Leber Congenital ...

6. aao.org aao.org/eyenet/article/leber-congenital-amaurosis-therapy

Small Trial Tests Drug Safety in People With LCA ... Eye Institute report that a small clinical trial involving an investigational gene therapy for Leber congenital amaurosis demonstrated safe.