Gene Therapy for Leber's Optic Atrophy

Recruiting at 2 trial locations

Overseen By Bin Li

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neurophth Therapeutics Inc

Must not be taking: Idebenone

Disqualifiers: Ocular surgery, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 80

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this clinical study is to evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to evaluate its safety and efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND4 mutation, with laboratory test showing G11778A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for \> 6 months and \< 10 years.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must stop using idebenone at least 7 days before participating. If you are taking idebenone and refuse to stop, you cannot join the trial.

What data supports the effectiveness of the treatment NR082 Injection for Leber's Optic Atrophy?

Research on a similar gene therapy using a virus to deliver a healthy gene into the eye showed that six out of nine patients had improved vision after nine months, with no serious side effects. This suggests that gene therapy could be a promising approach for treating Leber's Optic Atrophy. ^{1 2 3 4 5}

Is gene therapy for Leber's Optic Atrophy safe?

Gene therapy for Leber's Optic Atrophy, using treatments like rAAV2-ND4, has been tested in humans and found to be generally safe, with no serious safety problems observed in studies lasting up to three years. ^{1 3 4 5 6}

How does the NR082 Injection treatment differ from other treatments for Leber's Optic Atrophy?

The NR082 Injection is a gene therapy that uses a virus to deliver a healthy version of the ND4 gene directly into the eye, which is different from other treatments that do not target the genetic cause of the disease. This approach aims to improve vision by addressing the root cause of the condition, which is a mutation in the mitochondrial DNA. ^{1 3 4 5 7}

Eligibility Criteria

Adults aged 18-75 with Leber's Hereditary Optic Neuropathy (LHON) due to ND4 gene mutations, who have experienced vision loss for more than 6 months but less than 10 years. Participants must not be pregnant or breastfeeding and agree to use contraception for at least six months post-treatment. They should not have other eye diseases affecting vision or a history of certain treatments like ocular gene therapy.

Inclusion Criteria

I agree to use birth control for at least 6 months after treatment.

I am not pregnant or breastfeeding and either cannot become pregnant or agree to use contraception for 6 months after treatment.

Willingness to comply with the clinical study protocol and 5 years of long-term follow-up after administration

Exclusion Criteria

I have no other conditions or treatments known to cause vision loss, except LHON.

Any other exclusions determined by the investigator

I have had repeated eye inflammation or currently have it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding Treatment

Participants receive a single unilateral intravitreal injection of NR082 at varying doses to evaluate safety and efficacy

6 weeks

Weekly monitoring for dose-limiting toxicities

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Regular visits at Weeks 2, 6, 12, 26, 40, and 52

Long-term Follow-up

Extended monitoring of visual acuity and other parameters

Up to 260 weeks

Visits at Weeks 78, 104, 156, 208, and 260

Treatment Details

Interventions

• NR082 Injection

Trial Overview The trial is testing the safety and effectiveness of NR082, administered through a single intravitreal injection in one eye, for treating LHON caused by ND4 mutations. The goal is to see if this treatment can improve visual acuity in affected individuals.

Participant Groups

Group I: NR082 injection Experimental Treatment 2 Interventions

Potential doses at the dose-finding stage: * 0.5E9 vg, 0.05 mL/eye/dose (low dose) * 1.5E9 vg, 0.05 mL/eye/dose (starting dose) * 3.0E9 vg, 0.05 mL/eye/dose (intermediate dose) * 4.5E9 vg, 0.05 mL/eye/dose (high dose)

Who Is Running the Clinical Trial?

Neurophth Therapeutics Inc

Lead Sponsor

Trials

2

Recruited

20+

Findings from Research

The gene therapy for G11778A Leber hereditary optic neuropathy (LHON) demonstrated a favorable safety profile, with the only significant adverse event being uveitis, which occurred in 29% of participants but did not lead to lasting vision problems.

While some patients showed improvements in visual acuity, the overall efficacy of the treatment appears to be small and not related to the dose, indicating that further randomized studies are needed to confirm any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups. Lam, BL., Feuer, WJ., Davis, JL., et al.[2023]

References

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

Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Prognostic factors for visual acuity in patients with Leber's hereditary optic neuropathy after rAAV2-ND4 gene therapy. [2021]

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

Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups. [2023]

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

Gene Therapy for Leber Hereditary Optic Neuropathy: Low- and Medium-Dose Visual Results. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Factors associated with rapid improvement in visual acuity in patients with Leber's hereditary optic neuropathy after gene therapy. [2021]