Gene Therapy (ADVM-022) for Age-Related Macular Degeneration

Not currently recruiting at 44 trial locations

Overseen By Sharri Adams-Edwards

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Adverum Biotechnologies, Inc.

Must be taking: Anti-VEGF

Disqualifiers: Uncontrolled diabetes, Bleeding disorders, Glaucoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

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 ADVM-022 for individuals with wet age-related macular degeneration (nAMD), a condition that can cause vision loss due to abnormal blood vessels in the eye. The researchers aim to determine if a single injection of ADVM-022 can replace the frequent eye injections currently needed to manage the condition. The trial includes two groups, each receiving different doses of ADVM-022 to identify the optimal dose. Individuals who have regularly received anti-VEGF injections for nAMD and have benefited from them might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be under active anti-VEGF treatment for wet AMD to participate.

Is there any evidence suggesting that ADVM-022 is likely to be safe for humans?

Research has shown that ADVM-022, an experimental gene therapy for age-related macular degeneration, has been generally well-tolerated in studies so far. Early research, conducted before human testing, indicated that a single injection of ADVM-022 is safe over the long term and helps maintain levels of a protein called aflibercept, which is important for eye health.

Further evidence from human studies suggests that the treatment is safe and effective for managing this eye condition. While some side effects might occur, they are usually mild and manageable. Overall, ongoing research aims to confirm these safety findings and ensure that ADVM-022 is a good option for patients who need it. ^{1 2 3 4 5}

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

Unlike the standard treatments for age-related macular degeneration (AMD), which often involve repeated injections of anti-VEGF drugs to slow vision loss, ADVM-022 offers a novel approach with gene therapy. This treatment is delivered through a single intravitreal injection, which introduces a viral vector carrying a therapeutic gene directly into the eye. Researchers are excited about ADVM-022 because it has the potential to provide a long-lasting effect from just one injection, reducing the need for frequent treatments. This could significantly improve the quality of life for patients by minimizing the number of clinic visits and injections required.

What evidence suggests that ADVM-022 might be an effective treatment for age-related macular degeneration?

Studies have shown that ADVM-022, a gene therapy, might be a promising treatment for wet age-related macular degeneration (AMD). Research indicates that a single injection of ADVM-022 could have long-lasting effects, potentially reducing the need for frequent treatments. In early trials, patients experienced positive results at 24 weeks, with fewer treatments needed and improved vision. This therapy delivers a gene that helps the eye produce aflibercept, a protein that prevents abnormal blood vessel growth in the eye. The approach aims to maintain vision and reduce the number of eye injections needed. Overall, early findings suggest ADVM-022 could be an effective long-term option for managing wet AMD. Participants in this trial will receive one of two different doses of ADVM-022 to evaluate its effectiveness and safety. ^{3 5 6 7 8}

Who Is on the Research Team?

Adam Turpcu, PhD

Principal Investigator

Adverum Biotechnologies, Inc.

Are You a Good Fit for This Trial?

This trial is for people over 50 with wet age-related macular degeneration (nAMD) who've had at least 2-3 anti-VEGF injections in the past 4-6 months. They must have shown improvement from these treatments and have a certain level of vision acuity. Those with uncontrolled diseases, recent eye infections or surgeries, or other retinal issues can't participate.

Inclusion Criteria

I am 50 years old or older.

Willing and able to provide written, signed informed consent for this study

I am currently receiving anti-VEGF injections for wet AMD and have had at least 2 injections in the last 4 months.

Exclusion Criteria

I have had a retinal detachment or tear in the past.

I haven't had gene therapy or been part of eye studies recently.

I have had surgery on the back part of my eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of ADVM-022 at one of two doses with prophylactic corticosteroid treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and efficacy of the treatment

5 years

Regular visits over 5 years

What Are the Treatments Tested in This Trial?

Interventions

• ADVM-022

Trial Overview

ADVM-022, a gene therapy product designed to reduce treatment frequency for nAMD by providing sustained release of aflibercept after one injection. The study aims to see if this single treatment can maintain or improve patients' vision compared to regular anti-VEGF injections.

How Is the Trial Designed?

Group I: Dose 2 Experimental Treatment 1 Intervention

A single intravitreal injection of ADVM-022 6E10 vg/eye

Group II: Dose 1 Experimental Treatment 1 Intervention

A single intravitreal injection of ADVM-022 2E11 vg/eye

Who Is Running the Clinical Trial?

Adverum Biotechnologies, Inc.

Lead Sponsor

Trials

10

Recruited

560+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a phase I/II clinical trial involving 15 patients with choroideremia, subretinal delivery of the AAV2-hCHM vector was found to be safe, with no vector-related or systemic toxicities reported over a 2-year follow-up period.

Visual acuity remained stable within 15 letters of baseline in 13 out of 15 patients, although two patients experienced complications, indicating a potential risk associated with the injection procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Aleman, TS., Huckfeldt, RM., Serrano, LW., et al.[2022]

Recombinant adeno-associated viral (AAV) vectors are effective tools for gene therapy in retinal degeneration, showing long-term transgene expression and minimal side effects in various animal models.

AAV-mediated gene therapy has demonstrated significant recovery of retinal structure and visual function in models of inherited retinal degeneration, highlighting its potential for treating similar human conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus-vectored gene therapy for retinal disease. Dinculescu, A., Glushakova, L., Min, SH., et al.[2012]

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]

The study assessed the safety of a gene therapy using a recombinant adeno-associated virus vector (rAAV2-CB-hRPE65) in 12 patients (8 adults and 4 children) with retinal degeneration due to RPE65 mutations, finding no serious treatment-related adverse events after 2 years of follow-up.

Improvements in visual function were observed in 9 out of 12 patients, with the most significant gains in younger patients who had better baseline visual acuity, indicating potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Weleber, RG., Pennesi, ME., Wilson, DJ., et al.[2017]

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]

Subretinal gene therapy using rAAV2 carrying the RPE65 gene was found to be safe, with no systemic toxicity and only minor ocular adverse events related to the surgical procedure in a study of 15 patients aged 11 to 30.

Visual function improved in all treated patients, particularly in those with the lowest initial acuities, indicating that gene therapy can be effective for restoring vision in specific areas of the retina, although treatment of the fovea may carry risks without benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Jacobson, SG., Cideciyan, AV., Ratnakaram, R., et al.[2022]

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