Subretinal Injection for Leber Congenital Amaurosis

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

15 Participants Needed

Trial Summary

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 subretinal injection for Leber Congenital Amaurosis generally safe in humans?

Studies show that subretinal injections for Leber Congenital Amaurosis, using vectors like AAV2-RPE65, are generally safe in humans and animals. Some mild inflammation and immune responses were observed, but they were not severe, and patients tolerated the treatment well. ^{1 2 3 4 5}

How is the treatment SAR439483 for Leber Congenital Amaurosis different from other treatments?

SAR439483 is administered through subretinal injection, which allows for more direct delivery to the target cells in the eye compared to other methods. This approach is particularly beneficial for gene therapies, as it can provide more precise and efficient treatment for conditions like Leber Congenital Amaurosis. ^{1 2 3 6 7}

What is the purpose of this trial?

Primary Objective: To evaluate the safety and tolerability of ascending doses of ATSN-101 administered as a unilateral subretinal injection in patients with Leber Congenital Amaurosis (LCA) caused by autosomal recessive guanylate cyclase 2D (GUCY2D) mutations (GUCY2D-LCA). Secondary Objective: To evaluate the efficacy of ascending doses of ATSN-101 administered as a unilateral subretinal injection in patients with GUCY2D-LCA.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. [2012]

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

Perifoveal Chorioretinal Atrophy after Subretinal Voretigene Neparvovec-rzyl for RPE65-Mediated Leber Congenital Amaurosis. [2023]

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

Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. [2022]

4. United States 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. [2022]

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

Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases. [2017]

7. United States 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. [2021]