Gene Therapy for Leber Congenital Amaurosis

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

34 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment EDIT-101 for Leber Congenital Amaurosis?

Gene therapy for Leber's congenital amaurosis, particularly involving the RPE65 gene, has shown potential to improve vision and prevent further deterioration in patients with inherited retinal degeneration. Studies indicate that while initial improvements in vision can be achieved, the long-term effectiveness may vary, and further research is needed to optimize treatment strategies. ^{1 2 3 4 5}

Is gene therapy for Leber Congenital Amaurosis safe for humans?

Gene therapy for Leber Congenital Amaurosis has been shown to be generally safe in humans, with studies indicating no significant harmful immune responses and only minor adverse events like a transient rise in antibodies. Long-term safety data suggests that the treatment does not cause significant loss of treated cells and is well-tolerated. ^{2 3 5 6 7}

How is the treatment EDIT-101 for Leber Congenital Amaurosis different from other treatments?

EDIT-101 is a gene therapy that aims to correct the genetic cause of Leber Congenital Amaurosis by directly editing the DNA in the eye, which is different from other treatments like voretigene neparvovec (Luxturna) that use viral vectors to deliver a healthy copy of the gene. This approach is unique because it attempts to fix the underlying genetic mutation rather than just replacing the faulty gene. ^{1 2 4 8 9}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of EDIT-101 administered via subretinal injection in participants with LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991+1655A\>G in intron 26 of the CEP290 gene ("LCA10-IVS26").

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Treatment Potential for LCA5-Associated Leber Congenital Amaurosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. [2022]

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

Improvement and decline in vision with gene therapy in childhood blindness. [2022]

4. Hungary pubmed.ncbi.nlm.nih.gov

[Gene therapy treatment based on an ophthalmic indication in hereditary retinal dystrophy caused by RPE65 biallelic gene mutation.] [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Gene therapy for eye as regenerative medicine? Lessons from RPE65 gene therapy for Leber's Congenital Amaurosis. [2014]

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

Safety and efficacy of gene transfer for Leber's congenital amaurosis. [2022]

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

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. [2022]

8. 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]

9. China pubmed.ncbi.nlm.nih.gov

[Progress in gene therapy study of Leber congenital amaurosis]. [2012]