GT005 for Dry Age-Related Macular Degeneration

No longer recruiting at 14 trial locations

Overseen By Gyroscope Therapeutics Limited

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Gyroscope Therapeutics Limited

Must not be taking: Investigational products, Gene therapy

Disqualifiers: Choroidal neovascularisation, Diabetic retinopathy, Glaucoma, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called GT005 for individuals with dry age-related macular degeneration (AMD), a condition that causes vision loss. Researchers aim to determine how different doses of GT005, administered through eye procedures, can assist with macular atrophy, a common issue in dry AMD where an area of the retina deteriorates. Participants must have a clinical diagnosis of macular atrophy due to AMD in at least one eye. This trial offers those experiencing significant vision challenges due to AMD the potential for relief and the chance to contribute to medical advancements. As a Phase 1/Phase 2 trial, the research focuses on understanding how GT005 works in people and measuring its effectiveness in an initial, smaller group, providing participants the opportunity to be among the first to benefit from this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that GT005 has been safe and well-tolerated in people so far. Studies have found no serious side effects linked to the treatment. For example, one study noted a patient reaction, but it was not directly caused by the treatment. This suggests the treatment appears safe based on current information. Always consider consulting a healthcare provider for personalized advice about joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GT005 for dry age-related macular degeneration (AMD) because it offers a promising new approach compared to traditional treatments like vitamins and antioxidants. Unlike these standard options, GT005 is a gene therapy designed to deliver genetic material directly into the eye, potentially addressing the underlying causes of AMD. This is achieved through different delivery methods: transvitreal and an innovative Orbit Subretinal Delivery System, which could improve precision and effectiveness. By targeting the root cause of AMD, GT005 has the potential to preserve vision more effectively than current treatments.

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

Research shows that GT005 could be a promising treatment for dry age-related macular degeneration (AMD). This gene therapy uses a virus to deliver a genetic change that increases the production of complement factor I (CFI), a protein that helps reduce inflammation in the eye. Early studies found that GT005 is generally safe for patients, with no serious side effects directly linked to the treatment. While researchers are still collecting specific data on its effectiveness in improving vision, the therapy aims to slow or stop vision loss. Initial results suggest a positive effect, making GT005 a potential option for those experiencing vision problems due to AMD. ^{1 6 7 8 9}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults aged 55+ with Dry Age-Related Macular Degeneration (AMD) causing macular atrophy. Participants must have specific sizes of GA lesions in their eyes and meet certain vision acuity requirements. Women capable of childbearing need a negative pregnancy test, and all participants should be able to attend study visits.

Inclusion Criteria

I have been diagnosed with GA due to AMD in one eye and AMD in the other.

I am not pregnant and have taken a test in the last two weeks to confirm this, or I cannot become pregnant due to menopause or surgery.

My eye condition is fully visible in a specific eye test image.

Exclusion Criteria

I have not had eye surgery in the last 12 weeks, except for a specific laser procedure over 10 weeks ago.

Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant

Have a contraindication to the specified protocol corticosteroid regimen

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subretinal injection of GT005

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Regular visits (in-person)

Long-term follow-up

Participants have the option to be followed for a further 4 years to assess long-term safety and efficacy

192 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GT005

Trial Overview The FOCUS trial is testing GT005, delivered using the Orbit Subretinal Delivery System, on people with Dry AMD to see if it's safe and effective in treating macular atrophy. It's an open-label Phase I/II multicentre study where everyone receives the treatment.

How Is the Trial Designed?

Group I: GT005 5E10 vg with Orbit Subretinal Delivery System Experimental Treatment 1 Intervention

GT005 5E10 vg with Orbit Subretinal Delivery System

Group II: GT005 5E10 vg via Transvitreal Procedure Experimental Treatment 1 Intervention

GT005 5E10 vg via Transvitreal Procedure

Group III: GT005 2E11 vg with Orbit Subretinal Delivery System Experimental Treatment 1 Intervention

GT005 2E11 vg with Orbit Subretinal Delivery System

Group IV: GT005 2E11 vg via Transvitreal Procedure Experimental Treatment 1 Intervention

GT005 2E11 vg via Transvitreal Procedure

Group V: GT005 2E10 vg via Transvitreal Procedure Experimental Treatment 1 Intervention

GT005 2E10 vg via Transvitreal Procedure

Who Is Running the Clinical Trial?

Gyroscope Therapeutics Limited

Lead Sponsor

Trials

5

Recruited

720+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study of 130 eyes from 115 patients with age-related macular degeneration, those who received annual intravitreal anti-vascular endothelial growth factor injections maintained stable visual acuity over an average follow-up of 11.1 years.

Patients who did not receive at least one injection each year experienced a significant decline in visual acuity, highlighting the importance of continuous treatment for preserving vision in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TEN-YEAR FOLLOW-UP OF PATIENTS WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS. Starr, MR., Kung, FF., Mejia, CA., et al.[2021]

Antibody-based therapies have significantly improved the treatment of wet age-related macular degeneration (AMD), with innovative approaches like port delivery systems and bispecific antibodies showing promise in clinical trials.

While stem cell and gene therapies are still under investigation for both wet and dry AMD, they present potential benefits and risks that need further evaluation before clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration. Akyol, E., Lotery, A.[2020]

In a study of 593,277 patients with late dry age-related macular degeneration (dAMD), it was found that the majority had mild disease (64.4%) or intermediate disease (29.4%), with visual acuity (VA) decreasing as the disease progressed.

The annual probability of stable dAMD was high (82.1% for GA without subfoveal involvement to 92.3% for GA with subfoveal involvement), but the risk of progression to geographic atrophy or neovascular AMD increased significantly with disease severity, highlighting the need for effective treatments as patients advance in disease stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. Leng, T., Schwartz, J., Nimke, D., et al.[2023]

Only about 0.1% of the Polish population requires treatment for neovascular age-related macular degeneration (nAMD) when considering patients without severe irreversible eye damage, indicating a relatively low prevalence of this condition needing intervention.

The COVID-19 pandemic significantly impacted the enrollment in the national AMD therapeutic program, with a notable decrease in monthly enrollments, highlighting potential barriers to treatment access during health crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Need for Treatment of Neovascular Age-Related Macular Degeneration: A Study Based on the Polish National Registry. Teper, SJ., Nowińska, A., Figurska, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03846193

NCT03846193 | FOCUS: A Phase I/II First in Human Study ... The delivery was attempted in 28 pts but was only successful in 25 pts. Of 3 pts where the GT005 delivery via Orbit SDS arms was not successful, 2 were treated ...

2. escrs.org escrs.org/eurotimes-articles/gene-therapy-for-advanced-dry-amd/

Gene Therapy for Advanced Dry AMD The study is evaluating safety data at 48 weeks for the primary outcome. Secondary efficacy endpoints for analysis include anatomic and ...

3. stevenagecatalyst.com stevenagecatalyst.com/gyroscope-therapeutics-announces-presentation-positive-interim-phase-iii-data-investigational-gene-therapy-gt005-retina-society-annual-scientific-meet/

Gyroscope Therapeutics Announces Presentation Of ... Safety data from 28 patients showed GT005 continues to be well tolerated with no treatment-related serious adverse events. There was no evidence ...

4. withpower.com withpower.com/trial/phase-2-geographic-atrophy-11-2018-a4300

GT005 for Dry Age-Related Macular Degeneration This trial tested an eye injection treatment called GT005 for people with vision loss from Macular Atrophy due to AMD. The goal was to improve or maintain ...

5. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/focus-a-study-to-test-a-new-treatment-for-dry-amd/

FOCUS: A study to test a new treatment for dry AMD The overall objective is to evaluate the safety, dose response and efficacy of a gene therapy (GT005) in AMD patients. The study will be conducted in three ...

6. novartis.com novartis.com/news/gt005-ppy988-development-program-geographic-atrophy

GT005 (PPY988): Development Program in Geographic ... Novartis has decided to discontinue development of GT005 (PPY988) in Geographic Atrophy (GA) secondary to dry-Age-related Macular Degeneration (dry-AMD).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05481827

NCT05481827 | ORACLE: A Long-term Follow-up Study to ... The purpose of this study is to evaluate the long-term safety of GT005 in participants with Geographic Atrophy (GA) secondary to AMD who have been treated in an ...

8. retinatoday.com retinatoday.com/articles/2023-may-june/tackling-geographic-atrophy-with-gene-therapy

Tackling Geographic Atrophy With Gene Therapy Interim safety data suggested that GT005 was safe and well tolerated with no treatment-related serious adverse events.2 One patient experienced ...

9. clinicaltrials.eu clinicaltrials.eu/inn/gt005/

GT005: A Potential Treatment for Dry Age-related Macular ... GT005 is an investigational drug being studied in clinical trials for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration ( ...