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

Recruiting at 43 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

69 Participants Needed

Trial Summary

What is the purpose of this trial?

Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

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.

What data supports the effectiveness of the treatment ADVM-022 for age-related macular degeneration?

Research shows that ADVM-022, a gene therapy using a virus to deliver a treatment, can provide long-term benefits for wet age-related macular degeneration by maintaining high levels of a protein that prevents vision loss. In animal studies, a single injection of ADVM-022 was as effective as standard treatments in preventing vision problems, suggesting it could be a promising long-term option for patients. ^{1 2 3 4 5}

Is ADVM-022 gene therapy safe for humans?

ADVM-022, a gene therapy for eye conditions like age-related macular degeneration, has been tested in non-human primates and was well tolerated, showing no significant safety concerns. Clinical trials are ongoing to further evaluate its safety in humans. ^{2 3 6 7 8}

How is the treatment ADVM-022 different from other treatments for age-related macular degeneration?

ADVM-022 is unique because it uses gene therapy to deliver a long-lasting supply of a protein that blocks harmful blood vessel growth in the eye, potentially reducing the need for frequent injections that are common with other treatments. ^{1 2 3 5 9}

Research Team

Adam Turpcu, PhD

Principal Investigator

Adverum Biotechnologies, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. Netherlands 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. [2022]

2. United States 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. [2022]

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

Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies. [2023]

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

Adeno-associated virus-vectored gene therapy for retinal disease. [2012]

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

Comprehensive Preclinical Assessment of ADVM-022, an Intravitreal Anti-VEGF Gene Therapy for the Treatment of Neovascular AMD and Diabetic Macular Edema. [2021]

7. United States 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. [2017]

8. United States 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. [2022]

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

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. [2022]