NG101 Gene Therapy for Age-Related Macular Degeneration

Recruiting at 4 trial locations

Overseen By Gisuk Chang, Pharm.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neuracle Genetics, Inc

Must be taking: Anti-VEGF injections

Must not be taking: Anticoagulant therapy

Disqualifiers: Diabetes, Glaucoma, Retinal detachment, others

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

Compensation: Varies

Number of Visits: 26

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called NG101 to determine its safety and effectiveness for individuals with wet age-related macular degeneration (wAMD), a condition that causes vision loss. The treatment involves a one-time injection into the eye, with three different dosage levels under evaluation. Ideal participants have been diagnosed with wAMD and have received anti-VEGF injections, a common treatment for this condition, in the past six months. The goal is to identify a potential new treatment that could improve or stabilize vision in those affected by wAMD. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticoagulant therapy (blood thinners) that is medically necessary at least 2 weeks before the NG101 injection, except for low-dose aspirin used for prevention.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NG101 gene therapy, tested for wet age-related macular degeneration (wAMD), has a good safety record in early trials. So far, no side effects directly linked to the drug have been reported, suggesting that people tolerate the treatment well. Some serious side effects have occurred, but these also appeared in patients who received a placebo (a treatment with no active ingredients), indicating they might not be related to NG101.

Before human testing, lab studies also supported the safety of NG101. These studies demonstrated that the treatment could be safe and effective. NG101 uses a virus to deliver a gene that helps block a protein called VEGF, which plays a role in wAMD. This method has been safe in early trials, giving researchers hope about its safety in people.

Since this trial is in the early stages, the main goal is to understand how safe NG101 is for participants. As more people join the trial and more data is collected, researchers will gain a clearer picture of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for age-related macular degeneration?

Researchers are excited about NG101 gene therapy for age-related macular degeneration because it offers a novel approach by directly targeting the genetic causes of the disease. Unlike standard treatments such as anti-VEGF injections that need frequent administration, NG101 is delivered through a single subretinal injection, potentially reducing the need for repeated treatments. Additionally, NG101 uses an adeno-associated virus (AAV) vector to deliver the gene therapy, which could provide longer-lasting benefits by addressing the root cause of vision loss. With different dose groups being studied, there's hope for optimizing its effectiveness and safety.

What evidence suggests that this trial's treatments could be effective for wet age-related macular degeneration?

Research has shown that NG101 gene therapy could help treat wet age-related macular degeneration (wAMD). This therapy uses a modified virus to deliver a gene that enables the body to produce aflibercept, a protein that blocks VEGF, which causes harmful blood vessel growth in the eye. Studies have found that NG101 can be effective even at low doses, leading to a lasting presence of this beneficial protein. Early results suggest that this method might slow or improve vision loss in wAMD. While these findings are encouraging, more data from the various treatment arms in this trial, which test different doses of NG101, will provide a better understanding of its effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

Christopher D Riemann, MD

Principal Investigator

Neuracle Genetics, Inc. Medical Director

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 to 89 with wet age-related macular degeneration (wAMD) in one eye, who have had at least three anti-VEGF injections in the past six months. Participants must have undergone cataract surgery and not be pregnant or able to become pregnant without contraception. They should not have any severe systemic diseases, uncontrolled glaucoma, recent ocular surgeries, other retinal diseases, or be on certain anticoagulants.

Inclusion Criteria

My vision in the study eye is between 20/63 and 20/400, mainly due to wet AMD.

I've had 3 or more anti-VEGF injections in one eye within the last 6 months.

I am using effective birth control or am not able to have children, and I have a negative pregnancy test.

Exclusion Criteria

Any medically uncontrolled diabetes, defined as HbA1C > 8.0

My study eye has had a retinal detachment.

I have had eye melanoma in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a single subretinal injection of NG101 AAV gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

260 weeks

Multiple visits (in-person) at Weeks 24, 52, 104, 156, 208, and 260

Long-term follow-up

Extended monitoring for adverse events and efficacy

260 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NG101

Trial Overview The study tests NG101 AAV gene therapy given as a single dose through subretinal injection into one eye of patients with wAMD. It aims to assess the treatment's safety and initial effectiveness in improving vision affected by this condition.

How Is the Trial Designed?

Group I: NG101 Gene Therapy Group 3 Experimental Treatment 1 Intervention

Single subretinal injection of 8x10\^9 vector genomes of NG101 AAV gene therapy

Group II: NG101 Gene Therapy Group 2 Experimental Treatment 1 Intervention

Single subretinal injection of 3x10\^9 vector genomes of NG101 AAV gene therapy

Group III: NG101 Gene Therapy Group 1 Experimental Treatment 1 Intervention

Single subretinal injection of 1x10\^9 vector genomes of NG101 AAV gene therapy

Who Is Running the Clinical Trial?

Neuracle Genetics, Inc

Lead Sponsor

Trials

1

Recruited

20+

ORA, Inc.

Industry Sponsor

Trials

72

Recruited

9,200+

Stuart Abelson

ORA, Inc.

Chief Executive Officer since 2007

BSc in Neuroscience from Bates College, MBA from Northwestern University

Dr. Gustavo De Moraes

ORA, Inc.

Chief Medical Officer since 2022

MD, PhD in Ophthalmic Sciences, MPH in Biostatistics

Published Research Related to This Trial

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world, particularly affecting patients with neovascular AMD (nAMD) who currently rely on frequent and invasive anti-VEGF injections, which can lead to complications and treatment tolerance.

There is a pressing need for new therapies, especially for non-neovascular AMD, which accounts for 90% of cases and lacks approved treatments, highlighting the importance of developing improved drug delivery methods and sustainable clinical effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies and their delivery for treating age-related macular degeneration. Thomas, CN., Sim, DA., Lee, WH., et al.[2022]

Overexpression of basic fibroblast growth factor (FGF-2) through gene transfer using a recombinant adeno-associated virus (rAAV) was tested as a potential treatment to reduce photoreceptor cell death in a model of retinal degeneration caused by constant light exposure.

The effectiveness of this treatment was evaluated using morphometric analysis and electroretinographic assessments, indicating a focus on both structural and functional outcomes in the retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral-mediated FGF-2 treatment of the constant light damage model of photoreceptor degeneration. Lau, D., Flannery, J.[2019]

Gene therapy for neovascular age-related macular degeneration (nAMD) aims to provide a long-term solution by using adeno-associated virus (AAV) vectors to deliver anti-VEGF proteins, potentially reducing the need for frequent injections and improving visual outcomes.

Current research is focusing on optimizing gene delivery methods and exploring various therapeutic proteins, such as soluble fms-like tyrosine kinase-1 (sFLT-1) and other anti-angiogenic agents, to enhance the efficacy and safety of treatments for AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for age-related macular degeneration. Moore, NA., Bracha, P., Hussain, RM., et al.[2018]

KH631, a gene therapy using a recombinant adeno-associated virus vector, shows promise as a long-term treatment for neovascular age-related macular degeneration (nAMD) by enabling sustained expression of anti-VEGF proteins after a single injection.

In preclinical studies with non-human primates, a low dose of KH631 effectively prevented the formation and progression of severe choroidal neovascularization lesions for over 96 weeks, significantly reducing the treatment burden compared to frequent anti-VEGF injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. Ke, X., Jiang, H., Li, Q., et al.[2023]

Transplanting pigment epithelial cells that overexpress the anti-angiogenic factor PEDF could provide a new treatment for neovascular age-related macular degeneration (nvAMD), potentially reducing the need for frequent and invasive anti-VEGF injections.

The study demonstrated successful and stable expression of the PEDF gene in primary retinal pigment epithelial cells, suggesting a promising approach for long-term therapy in nvAMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. Thumann, G., Harmening, N., Prat-Souteyrand, C., et al.[2022]

Gene therapy for neovascular age-related macular degeneration (nAMD) shows promise as a long-term solution to reduce the need for frequent and costly intravitreal injections, which are currently the standard treatment.

Early phase clinical trials have reported encouraging results for gene therapy approaches, although there are ongoing debates about the best treatment targets, administration methods, and safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions. Guimaraes, TAC., Georgiou, M., Bainbridge, JWB., et al.[2021]

The gene therapy rAAV.sFLT-1 was found to be safe and well tolerated in a phase 1 trial involving nine patients with wet age-related macular degeneration, with no drug-related adverse events reported.

A significant portion of the treatment group (67%) did not require any rescue injections after the therapy, suggesting that a single subretinal injection could provide long-term benefits compared to the frequent injections currently needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Rakoczy, EP., Lai, CM., Magno, AL., et al.[2022]

In a Phase 2a trial with 32 patients suffering from wet age-related macular degeneration, the gene therapy rAAV.sFLT-1 was found to be safe, with mainly self-resolving ocular adverse events and no serious safety concerns linked to the treatment.

Patients receiving rAAV.sFLT-1 showed a median improvement in visual acuity compared to the control group, with 57% maintaining or improving vision, and they required fewer ranibizumab retreatments, suggesting that this gene therapy could be a promising option for managing wAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. Constable, IJ., Pierce, CM., Lai, CM., et al.[2022]

Adeno-associated viral vectors (AAVs) can trigger immune responses in the eye, leading to toxicity in certain ocular cell types, particularly the retinal pigment epithelium (RPE) and photoreceptors, as shown in a study using subretinal injections in mice.

The study found that the toxicity of AAVs is linked to specific cis-regulatory sequences and promoter types, with certain promoters causing damage while photoreceptor-specific promoters were safe at high doses, suggesting that careful design of AAV vectors can enhance their safety and therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV cis-regulatory sequences are correlated with ocular toxicity. Xiong, W., Wu, DM., Xue, Y., et al.[2020]

In a phase 1 and 2A clinical trial involving 6 elderly patients with wet AMD, the gene therapy rAAV.sFlt-1 was found to be well tolerated with a favorable safety profile, showing no drug-related adverse events and only mild, self-resolving procedure-related issues.

Four out of six patients treated with rAAV.sFlt-1 maintained better vision and retinal health compared to the control group, suggesting that this gene therapy could serve as a promising alternative to traditional treatments like ranibizumab for wet AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Therapy for Age-Related Macular Degeneration. Constable, IJ., Blumenkranz, MS., Schwartz, SD., et al.[2017]

The rAAV.sFLT-1 gene therapy for wet age-related macular degeneration was well tolerated in a small group of elderly patients, with no serious adverse events directly linked to the treatment, despite some reported adverse events.

While the study did not find statistically significant improvements in visual acuity, a notable percentage of patients receiving gene therapy maintained their baseline vision over three years, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration. Rakoczy, EP., Magno, AL., Lai, CM., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11615598/

Preclinical Eval: NG101 AAV Gene Therapy for Wet AMD Overall, these findings suggest that NG101, with its efficacy at low doses and sustained expression, is a promising therapeutic candidate for wAMD. Keywords: ...

2. delta.larvol.com delta.larvol.com/Products/?ProductId=933b9607-c2c5-49d3-85c6-7983aacdad79

NG101 / Neuracle Sci, Reyon Pharma - Gene Therapies Gene therapy • P1/2 data • Preclinical • Age-related Macular Degeneration ... NG101, a potential AAV gene therapy for wet age-related macular degeneration.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39634790/

NG101: AAV Gene Therapy for Wet AMD We present findings on the safety and efficacy of NG101, a recombinant adeno-associated virus (rAAV) vector encoding aflibercept, an anti-VEGF agent, for wAMD ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05984927

NG101 AAV Gene Therapy in Subjects With Wet Age ... This study will evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy administered by subretinal injections into a single ...

5. synapse.patsnap.com synapse.patsnap.com/drug/79fcb08cd6654ebf9672bbf0c3da7d86

NG-101(Reyonpharm) - Drug Targets, Indications, Patents NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of ...

6. withpower.com withpower.com/trial/ng101-gene-therapy-for-age-related-macular-degeneration-703f3

NG101 Gene Therapy for Age-Related Macular ... Gene therapy using rAAV.sFlt-1 for age-related macular degeneration has shown a favorable safety profile in early clinical trials, with no drug-related adverse ...