Is there any clinical trial called VISION in the United States for geographic atrophy?

Overview of Geographic Atrophy Geographic atrophy (GA)) is an advanced form of age‑related macular degeneration (AMD) characterized by progressive, irreversible loss of the retinal pigment epithelium, photoreceptors, and choriocapillaris. This degeneration leads to significant visual impairment over time even when early central vision may be preserved. GA is a major cause of legal blindness in aging populations worldwide, and because of its slow but relentless progression, early detection and intervention are critical. Evidence suggests that various underlying mechanisms—including complement-mediated inflammation, oxidative stress, and genetic predisposition—may contribute to the pathogenesis of GA.

Definition and Causes
GA is defined by the presence of well‑demarcated areas of atrophy in the macula that gradually enlarge. The condition is primarily seen in elderly individuals and is driven by a combination of genetic factors (such as complement pathway variants), environmental risks (like smoking), and metabolic changes in the retinal tissues. The characteristic loss of the retinal pigment epithelium and photoreceptors distinguishes GA from other forms of AMD. As the disease advances, the remaining areas of functioning retina may not be adequate to support normal visual tasks, leading to difficulties in activities such as reading, driving, or recognizing faces.

Current Treatment Options
Despite the significant disease burden, treatment options for GA have historically been very limited. Until recently, no interventions could halt or reverse the atrophic process. However, emerging treatments such as complement inhibitors (for example, pegcetacoplan and avacincaptad pegol) have shown promise in reducing the rate of GA lesion growth in late‑phase clinical trials. In addition, research efforts are exploring cell‑based therapies, gene therapies, and neuroprotective interventions aimed at preserving the remaining retinal structure and slowing functional decline.

Clinical Trials for Geographic Atrophy
Clinical trials offer an essential platform for assessing the efficacy and safety of emerging therapeutic strategies, and in the context of GA, they aim to find interventions that can slow lesion expansion and preserve vision over time. These trials play a vital role in moving innovations from the laboratory to the clinic and in addressing an area of unmet medical need.

Importance and Objectives
The primary objective of clinical trials in GA is to evaluate whether therapeutic agents can slow the progression of atrophic lesions and thereby delay the onset of severe vision loss. Clinical trials not only assess anatomical endpoints (such as changes in lesion size as measured by imaging modalities like fundus autofluorescence and OCT) but increasingly also incorporate functional endpoints that capture patient‑reported outcomes and quality of life. Given that best‑corrected visual acuity (BCVA) is sometimes preserved until foveal involvement, trials are designed to incorporate additional outcome measures that reflect patients’ everyday visual function.

Overview of Major Trials
Several major clinical trials have contributed to our understanding of emerging treatments for GA. Notable studies include the phase 2 FILLY trial for pegcetacoplan, which demonstrated a dose‑dependent reduction in GA lesion growth, and subsequent phase 3 trials such as DERBY and OAKS that further investigated the efficacy and safety of this complement C3 inhibitor. Other trials assessing agents like avacincaptad pegol have also provided valuable information regarding therapeutic effects. Beyond pharmacologic inhibition of the complement cascade, clinical investigations are ongoing for cell‑based therapies, gene therapies delivered either intravitreally or by other routes, and even novel methods that may combine imaging biomarkers with functional assessments.

VISION Clinical Trial
One clinical study that has emerged in the landscape of GA therapies is the trial known as VISION. Unlike many of the other GA trials that evaluate pharmacologic agents administered via intravitreal injections, the VISION trial takes a different approach by using gene therapy‐based methods.

Trial Objectives and Design
The VISION study is identified as a Phase 1/2, first‑in‑human, multi‑arm, dose‑escalation clinical trial. Its official title is:
"A Phase 1/2, First-in-Human, Multi-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of an Adeno-Associated Virus Vector VV-14295 Administered Suprachoroidally with the Everads Injector in Adults with Geographic Atrophy Secondary to Age-related Macular Degeneration (the VISION Study)."

The trial’s design is innovative and reflects the modern strategies employed to deliver genetic material safely into the targeted tissues. In this study, an adeno‑associated virus (AAV) vector—specifically designated VV‑14295—is administered via suprachoroidal injection using a dedicated injector (the Everads Injector). The investigational method is intended not only to evaluate the safety and tolerability of this novel gene therapy approach but also to provide early indications of efficacy in modifying disease progression. The dose‑escalation, multi‑arm design allows researchers to carefully monitor adverse events and determine the optimal dosing regimen for further clinical evaluation. This study represents a significant departure from conventional small‑molecule or antibody‑based interventions and instead focuses on the potential long‑term benefits of gene therapy for GA.

Key Inclusion and Exclusion Criteria
While the detailed inclusion and exclusion criteria for the VISION trial have not been extensively published in the provided references, the design as a first‑in‑human and dose‑escalation study implies several standard key criteria:

- Inclusion Criteria:
- Adult patients with a confirmed diagnosis of GA secondary to age‑related macular degeneration.
- Evidence of GA lesions meeting a minimum size requirement on imaging modalities such as fundus autofluorescence or OCT.
- Sufficient visual function (even if not compromised by foveal involvement) to permit efficacy assessments.
- Willingness to comply with study procedures and follow-up visits.
- Provision of informed consent.

- Exclusion Criteria:
- Presence of confounding ocular pathologies (such as other retinal dystrophies or active ocular inflammation) that could interfere with the interpretation of the treatment effect.
- Previous participation in other experimental gene therapy trials or recent ocular interventions that might confound the study outcomes.
- Systemic conditions that might increase the risk of adverse events associated with gene therapy.
- Contraindications to intraocular or suprachoroidal injections.

These criteria ensure that the enrolled population is appropriate for evaluating both the safety and the early indications of efficacy of the AAV-mediated gene therapeutic approach.

Current Status and Findings
Given the status as a Phase 1/2 study, the primary endpoints of the VISION trial are focused on safety and tolerability rather than on definitive efficacy outcomes. The study is intended to determine whether the suprachoroidal delivery of the investigational vector VV‑14295 is feasible and safe in adult patients with GA, with further assessments of anatomical markers (such as changes in GA lesion area) and, potentially, functional visual outcomes.

At the time of the information provided by synapse, the VISION trial is in its early clinical stages. The trial’s registration details (including the start date encoded in epoch time) indicate that it has been initiated, and patients are being enrolled according to the predefined criteria. Early data from such studies typically focus on the incidence of adverse events, any dose‑limiting toxicities, and preliminary imaging results that may suggest a slowing of GA lesion progression. Although detailed published findings of the VISION trial are not yet available, the study is positioned to contribute significantly to the gene therapy pipeline for GA by providing critical initial safety data and guiding further dose and efficacy studies.

Implications and Future Directions
The emergence of the VISION trial has several implications for the treatment of GA and for the broader field of retinal gene therapy.

Potential Impact on Treatment
The VISION trial represents an innovative approach to treating GA by leveraging gene therapy technology. If the trial demonstrates that suprachoroidal delivery of the AAV vector is safe and shows early evidence of efficacy, it may open the door for a paradigm shift in the management of GA. Unlike traditional pharmacologic treatments that require repeated intravitreal injections, gene therapy has the potential to provide long‑term effects from a single or limited number of administrations. This could dramatically reduce the treatment burden on patients and caregivers and improve adherence compared to current therapies that may only slow progression without reversing damage. Furthermore, the successful translation of gene therapy for GA could stimulate further research into combination therapies that target multiple pathways involved in retinal degeneration, thereby offering a more comprehensive approach to preserving visual function.

Future Research and Trials
The outcomes of the VISION trial will likely influence future clinical research in several ways:

1. Optimization of Gene Therapy Delivery:
The unique administration via the suprachoroidal space, facilitated by the Everads Injector, requires validation in terms of both its precision and safety. Future research may aim to optimize delivery techniques, refine dosing strategies, or compare suprachoroidal delivery with other routes such as intravitreal or subretinal injections.

2. Biomarker Development and Efficacy Assessment:
As the field evolves, there will be an increasing need for robust biomarkers that correlate well with clinical outcomes. Future trials could expand on the findings of the VISION study by including comprehensive imaging biomarkers (e.g., OCT‑measured changes in retinal layers) and functional endpoints that capture quality‑of‑life improvements.

3. Long-term Outcomes and Comparative Effectiveness:
Phase 1/2 studies such as VISION are designed to establish safety and preliminary efficacy. Future larger, randomized controlled trials will need to compare gene therapy approaches with current standard‑of‑care treatments, such as complement inhibitors, and assess long‑term outcomes including progression rate of GA lesions and maintenance of visual function.

4. Regulatory and Commercial Considerations:
Positive early results from the VISION trial could accelerate regulatory pathways and attract further investment into retinal gene therapies. In the broader context, this could lead to the development of commercially available products that offer a one‑time or infrequent dosing regimen, transforming the treatment landscape for a vast number of patients with GA.

Conclusion
In summary, there is indeed a clinical trial known as the VISION study in the United States that is investigating a gene therapy‐based approach for the treatment of geographic atrophy secondary to age‑related macular degeneration. This Phase 1/2, first‑in‑human, multi‑arm, dose‑escalation trial employs an adeno‑associated virus vector (VV‑14295) administered by a novel suprachoroidal injection technique using the Everads Injector. The trial primarily focuses on establishing the safety and tolerability of the gene therapy while providing early indications of efficacy. Although detailed results have not yet been publicly reported, the VISION trial represents an important innovation in the field, with the potential to reduce the treatment burden for patients and offer long‑term therapeutic benefits. From a broader perspective, the trial not only contributes to the evolving landscape of GA treatments—where agents such as complement inhibitors have recently shown promise—but also establishes a framework for future research exploring gene‑based interventions and novel drug‑delivery methods in ophthalmology. Continued emphasis on rigorous clinical trial design, integration of advanced imaging and functional assessment, and collaborative translational research will be key to harnessing the full potential of these emerging therapies. Ultimately, the VISION trial is expected to influence future clinical strategies and may pave the way for transformative treatments that address both the biological and quality‑of‑life challenges posed by geographic atrophy.