Gene Therapy for Leber's Optic Atrophy

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy, NR082, for individuals with vision loss due to Leber's Hereditary Optic Neuropathy (LHON) from the ND4 gene mutation. The aim is to assess the safety and effectiveness of this treatment in improving eyesight. The trial seeks participants who have experienced vision loss for more than 6 months but less than 10 years and have been diagnosed with the ND4 mutation in a certified lab. Participants will receive a single injection in one eye and must be willing to follow the study's requirements for several years. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking advancements in vision restoration.

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.

Is there any evidence suggesting that NR082 injection is likely to be safe for humans?

Research has shown that NR082 is safe in clinical studies. It is advancing into more trials because patients have tolerated it well. Early results suggest no major safety issues with the doses tested.

Another study found no new safety problems, allowing the treatment to be tested with more patients. Researchers closely monitor the treatment at different stages to ensure its safety. Always consult a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Leber's Optic Atrophy, which primarily focus on managing symptoms and slowing progression, the NR082 injection is a gene therapy that directly targets the genetic cause of the disease. This innovative approach uses a viral vector to deliver a healthy copy of the affected gene to the eye, potentially restoring vision rather than just preserving it. Researchers are excited because this method could offer a more effective and lasting solution, potentially transforming the treatment landscape for patients with this condition.

What evidence suggests that NR082 injection might be an effective treatment for LHON?

Research shows that NR082, which participants in this trial will receive, is a promising new treatment for Leber's Hereditary Optic Neuropathy (LHON), a condition caused by a specific gene mutation. This treatment uses a harmless virus to deliver healthy genes into the eye, potentially improving vision. Studies have found that similar treatments can lead to lasting vision improvement for several years. Currently, no approved treatments exist for LHON, but early research suggests that NR082 could bring new hope to those affected. The ongoing research aims to determine the most effective dose for this treatment. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. neurophth.com neurophth.com/en/NewsD-358.html

NEWS “There is currently no approved effective treatment for LHON. NR082 leverage gene therapy strategy and use recombinant adeno-associated virus as the vector to ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39699886/

Five-Year Outcomes of Lenadogene Nolparvovec Gene ... Lenadogene nolparvovec demonstrated a sustained bilateral improvement in BCVA and a good safety profile up to 5 years after treatment.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04912843?cond=Leber%20hereditary%20optic%20neuropathy%20OR%20%22Leber%20Hereditary%20optic%20atrophy%22%20OR%20%22%20Leber%20optic%20atrophy%22%20OR%20%22%20Leber's%20hereditary%20optic%20neuropathy%22%20OR%20%22%20Leber's%20optic%20atrophy%22%20OR%20%22%20LHON%22&aggFilters=status:not%20rec&viewType=Table&rank=1

Gene Therapy Clinical Trial for the Treatment Of Leber's ... The objective of this clinical study is to select the optimal dose and evaluate the safety and efficacy of NR082 in treatment of LHON caused by ...

4. cgtlive.com cgtlive.com/view/neurophth-tackling-lhon-nd4-with-gene-therapy-nr082-phase-gold-trial

Neurophth is Tackling LHON-ND4 With Gene Therapy ... “There is currently no approved effective treatment for LHON,” Xiaoning Guo, the chief medical officer of Neurophth, said in a September 2022 ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/partner/umdf/trial/316075

Gene Therapy Clinical Trial for the Treatment Of Leber's ... The objective of this clinical study is to select the optimal dose and evaluate the safety and efficacy of NR082 in treatment of LHON caused ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/condition/586/lebers-hereditary-optic-neuropathy-lhon

Leber's Hereditary Optic Neuropathy (LHON) The safety of the starting dose will first be performed in 6 evaluable subjects. ... If there is no new safety concern evaluated by the SRC, the randomized, ...

7. cgtlive.com cgtlive.com/view/new-leber-hereditary-optic-neuropathy-gene-therapy-trial-doses-first-patient

New Leber Hereditary Optic Neuropathy Gene Therapy ... “NR082 has shown promising safety and efficacy data in all clinical work to date and is officially advanced into a Phase 3 trial. Ophthalmic ...

8. link.springer.com link.springer.com/chapter/10.1007/978-3-031-96416-9_17

Leber's Hereditary Optic Neuropathy Further assess the efficacy and safety following intravitreal injection of NR082 at different doses. Descriptions of safety evaluation at Weeks 26, 40, and 52.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9405679/

Leber Hereditary Optic Neuropathy - PubMed Central - NIH ... injection control study to verify the efficacy and safety of NR082 (rAAV2-ND4). Due to the rapid development of gene therapy for LHON, the ...