Gene Therapy for Leber Congenital Amaurosis

Not currently recruiting at 4 trial locations

Overseen By Editas Medicine's Clinical Trial Team

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Editas Medicine, Inc.

Must not be taking: Corticosteroids

Disqualifiers: Other mutations, Infections, Steroid response, 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 new gene therapy called EDIT-101 to determine its safety and effectiveness for individuals with Leber Congenital Amaurosis 10 (LCA10), a rare eye condition. Specific changes in the CEP290 gene cause this condition, leading to severe vision loss. Participants will receive a single dose of the treatment directly into the eye. The trial seeks individuals aged 3 and older with severe vision problems due to LCA10 and a specific genetic mutation. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must be willing to take oral prednisone, which might interact with other medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that EDIT-101, the treatment under study, was safe in earlier studies, with most patients not experiencing serious side effects. These studies also found some signs of potential vision improvement, which is promising. Although the treatment is still being tested, these early results suggest it is generally safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for LCA?

Unlike standard treatments for Leber Congenital Amaurosis, which often involve vision aids or vitamin supplements, EDIT-101 is a groundbreaking gene therapy targeting the root cause of the disease. This treatment works by using CRISPR technology to directly edit the genetic mutations responsible for the condition, offering the potential for a more permanent solution. Researchers are excited because this approach could restore vision by correcting the genetic defect itself, rather than just managing symptoms. Additionally, the delivery method via subretinal injection ensures precise targeting of the affected cells, which is a significant advancement in treatment precision.

What evidence suggests that EDIT-101 could be an effective treatment for LCA10?

Research has shown that EDIT-101 holds promise for treating Leber congenital amaurosis 10 (LCA10), a serious eye disorder. In early animal tests, EDIT-101 achieved the necessary level of gene editing to improve vision. Initial results from human trials suggest that patients treated with EDIT-101 experienced consistent improvements in eyesight clarity, as measured by best-corrected visual acuity (BCVA). Furthermore, the treatment has proven safe at different dose levels, which are being tested in this trial across various arms, including Adults High Dose and Pediatric Middle Dose. These findings support the potential effectiveness of EDIT-101 for individuals with LCA10. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for males and females aged 3 or older with a specific genetic form of retinal degeneration (LCA10) due to mutations in the CEP290 gene. Participants must have severe vision loss, but not other disease-causing mutations or conditions that could affect the study's outcome like recent vaccinations, unwillingness to take oral prednisone, or prior similar treatments.

Inclusion Criteria

I am 3 years or older with a specific genetic eye condition.

The participant has very poor vision in the study eye, with a measurement of 20/800 or worse.

Participants, other than those specifically being studied, must have a visual acuity between 1.0 and 3.0 logMAR in the eye being studied.

Exclusion Criteria

I have not had any vaccinations in the last 28 days.

I passed the hardest level of a mobility test.

I have never received gene therapy or oligonucleotide treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single ascending dose of EDIT-101 administered via subretinal injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• EDIT-101

Trial Overview The trial tests EDIT-101 delivered through an injection into the retina for safety and effectiveness. It targets patients with LCA10 caused by certain CEP290 gene mutations. The study involves giving participants one dose of EDIT-101 and observing its effects on their condition.

How Is the Trial Designed?

Group I: Pediatric Middle Dose Experimental Treatment 1 Intervention

Single dose of EDIT-101 administered by subretinal injection surgery

Group II: Pediatric High Dose Experimental Treatment 1 Intervention

Single dose of EDIT-101 administered by subretinal injection surgery

Group III: Adults Middle Dose Experimental Treatment 1 Intervention

Single dose of EDIT-101 administered by subretinal injection surgery

Group IV: Adults Low Dose Experimental Treatment 1 Intervention

Single dose of EDIT-101 administered by subretinal injection surgery

Group V: Adults High Dose Experimental Treatment 1 Intervention

Single dose of EDIT-101 administered by subretinal injection surgery

Who Is Running the Clinical Trial?

Editas Medicine, Inc.

Lead Sponsor

Trials

5

Recruited

170+

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]

Adeno-associated viral (AAV) vector-mediated gene therapy for Leber congenital amaurosis (LCA) has shown promising results, particularly with the successful Phase I clinical trials for RPE65 gene therapy, marking a significant advancement in retinal gene therapy.

The progress in gene therapy for LCA not only highlights its potential effectiveness in treating this specific condition but also opens up possibilities for curing other hereditary retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Progress in gene therapy study of Leber congenital amaurosis]. Pan, SS., Zheng, QX., Li, WS., et al.[2012]

Retinal gene therapy for Leber's congenital amaurosis has shown initial safety and efficacy, with vision improvements maintained for up to 6 years in some patients.

However, long-term follow-up revealed that while vision improvements were sustained, the rate of photoreceptor loss in treated retinas was similar to that in untreated retinas, indicating a potential limitation in the therapy's long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement and decline in vision with gene therapy in childhood blindness. Jacobson, SG., Cideciyan, AV., Roman, AJ., et al.[2022]

Gene therapy using AAV vectors to deliver the RPE65 gene has been shown to be safe and effective for treating Leber's congenital amaurosis (LCA), with positive effects on retinal and visual function lasting at least 1.5 years in patients.

The treatment did not trigger significant immune responses against the RPE65 protein, indicating that AAV-mediated gene transfer can maintain its therapeutic effects without causing harm to the retinal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Simonelli, F., Maguire, AM., Testa, F., et al.[2022]

Gene augmentation therapy using AAV8-hLCA5 can effectively rescue photoreceptor function and structure in a mouse model of Leber congenital amaurosis (LCA) if administered before postnatal day 30, highlighting a critical therapeutic window.

Patients with LCA5 mutations retain some photoreceptors in the central retina, suggesting that similar gene therapy could be beneficial for them, as their condition mirrors the severe degeneration seen in the mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Potential for LCA5-Associated Leber Congenital Amaurosis. Uyhazi, KE., Aravand, P., Bell, BA., et al.[2021]

Citations

1. ir.editasmedicine.com ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-positive-initial-clinical-data-ongoing

Editas Medicine Announces Positive Initial Clinical Data ... EDIT-101 is under development for the treatment of blindness due to Leber congenital amaurosis 10 (LCA10), a CEP290-related retinal degenerative disorder.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309915

Gene Editing for CEP290-Associated Retinal Degeneration In preclinical models, treatment with EDIT-101 resulted in sustained CEP290 gene editing at levels that met the therapeutic threshold. The ...

3. 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.

4. ir.editasmedicine.com ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-clinical-data-demonstrating-proof

Editas Medicine Announces Clinical Data Demonstrating ... EDIT-101 demonstrates a favorable safety profile across all dose cohorts. Preliminary efficacy signals of consistent improvement in BCVA ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03872479

Single Ascending Dose Study in Participants With LCA10 The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of EDIT-101 administered via subretinal ...

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

Safety and efficacy of ATSN-101 in patients with Leber ... Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, ...

7. 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 ...