RGX-314 for Diabetic Macular Edema

(ELAAVATE Trial)

Overseen By Clinical Research Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sierra Eye Associates

Must be taking: Aflibercept

Must not be taking: Intravitreal steroids

Disqualifiers: Women of childbearing potential, 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: Unknown

Duration: 52 weeks

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 treatment called RGX-314 for individuals with diabetic macular edema, a condition that causes vision problems due to diabetes. Researchers aim to determine if RGX-314 can improve vision compared to the existing treatment, aflibercept (Eylea). Participants will receive varying doses of RGX-314 or the standard aflibercept treatment to compare outcomes. The trial seeks individuals with type I or type II diabetes who have vision issues primarily due to diabetic macular edema and have previously responded to aflibercept treatment. 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 information does not specify if you need to stop taking your current medications. However, if you have had certain eye treatments recently, like intravitreal steroid injections, you may not be eligible to participate.

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

Research has shown that RGX-314 has been promising in earlier studies. It has been tested for eye conditions such as neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). In these studies, RGX-314 served as a gene therapy, using a modified virus to help eye cells produce a protein that reduces harmful blood vessel growth.

The safety results have been encouraging. Patients who received RGX-314 generally tolerated it well. Most side effects were mild, including temporary eye discomfort. No serious side effects were directly linked to the treatment. These findings suggest that RGX-314 could be a safe option for patients with eye conditions like diabetic macular edema, though ongoing research will provide more insights. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RGX-314 for diabetic macular edema because it offers a novel approach compared to standard treatments like anti-VEGF injections, typically represented by drugs such as Eylea. Unlike these options, RGX-314 uses a gene therapy method by delivering an anti-VEGF fab transgene via an AAV8 vector. This innovative delivery could potentially reduce the need for frequent injections, making it a more convenient option for patients. Additionally, the two different doses of RGX-314 being tested may provide further insights into optimizing its effectiveness and safety.

What evidence suggests that this trial's treatments could be effective for Diabetic Macular Edema?

Research has shown that RGX-314 could help treat diabetic macular edema (DME). In this trial, participants will receive either RGX-314 at Dose 1 or Dose 2, or they will be in the Aflibercept treatment arm. Earlier studies demonstrated that a single injection of RGX-314 gene therapy improved related eye conditions, such as diabetic retinopathy. The treatment uses a harmless virus to deliver a gene that blocks a protein responsible for unwanted blood vessel growth in the eye, reducing swelling and improving vision. Early results from other trials have shown that RGX-314 can be safe and effective for eye diseases. This suggests it might offer lasting benefits for people with DME with just one treatment. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with a condition called Center Involved - Diabetic Macular Edema (CI-DME), which affects the retina in people with diabetes. Specific eligibility criteria are not provided, but typically participants should have CI-DME and meet certain health standards.

Inclusion Criteria

HbA1c ≤12%

Provide written informed consent

BCVA in study eye 78 to 25 ETDRS letters (~20/32 to 20/320) at screening

Exclusion Criteria

Participation in any other gene therapy study or receipt of any investigational product within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is longer, or any plans to use an investigational product within 6 months following enrollment

Presence of an implant in the study eye at screening (excluding intraocular lens)

Any condition in the investigator's opinion that could limit VA improvement in the study eye

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RGX-314 gene therapy or Aflibercept treatment for diabetic macular edema

52 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RGX-314

Trial Overview The study is testing two different doses of an experimental treatment called RGX-314 against a standard treatment, Aflibercept (2.0 mg). It's a phase 2 trial where patients are openly assigned to one of the treatments to compare effectiveness and safety.

How Is the Trial Designed?

Group I: Treatment Arm (Dose 2) Experimental Treatment 1 Intervention

Genetic: RGX-314 Dose 2 -AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)

Group II: RGX-314 Treatment Arm (Dose 1) Experimental Treatment 1 Intervention

Genetic: RGX-314 Dose 1 \- AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)

Group III: Aflibercept Treatment Arm Active Control 1 Intervention

Biological: Aflibercept IVT * Commercially available Active Comparator * Other Names: Eylea

Who Is Running the Clinical Trial?

Sierra Eye Associates

Lead Sponsor

REGENXBIO Inc.

Industry Sponsor

Trials

25

Recruited

3,100+

Citations

1. regenxbio.com regenxbio.com/getattachment/9463317c-3806-4434-aa79-898162f2665a/Barakat_03Nov23_ABBV-RGX-314-SCS-ALTITUDE-AAO-2023-FINAL_02Nov23.pdf?lang=en-US&ext=.pdf

P119172_ABBV-RGX-314 SCS ALTITUDE AAO 2023 ... PDR = Proliferative Diabetic Retinopathy. One time, in-office injection of gene therapy could potentially provide long-lasting improvement in DR ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06942520

Study Details | NCT06942520 | Phase 2 Trial of RGX-314 ... This Phase 2 trial is an open label, randomized, active controlled, dose-ranging trial to allow for preliminary safety and efficacy data on subretinal (SR) ...

3. healio.com healio.com/news/ophthalmology/20240125/oneyear-trial-outcomes-demonstrate-efficacy-of-abbvrgx314-gene-therapy-for-dr

One-year trial outcomes demonstrate efficacy of ABBV- ... One-year results of the phase 2 ALTITUDE trial showed efficacy and safety of a one-time in-office injection of ABBV-RGX-314 for the treatment of diabetic ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)00310-6/abstract

Gene therapy for neovascular age-related macular ... We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD.

5. regenxbio.com regenxbio.com/getattachment/696f66f4-96f1-4b5b-b5ad-d2870ae7e838/SR-Fellow-Eye-AAO_Khanani-2024_FINAL_.pdf?lang=en-US&ext=.pdf

Subretinal Delivery of Investigational ABBV-RGX-314 as a ... ABBV-RGX-314 for Treatment of Neovascular Age-related Macular Degeneration (nAMD) ... GENE Anti-VEGF fab. ROUTES OF. ADMINISTRATION. MECHANISM.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04567550

Study Details | NCT04567550 | RGX-314 Gene Therapy ... This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 gene therapy in subjects with DR

7. retinatoday.com retinatoday.com/articles/2019-nov-dec/gene-therapy-approach-demonstrated-safety-with-durable-effect-in-interim-wet-amd-trial-results

Gene Therapy Approach Demonstrated Safety With ... The innovation of RGX-314 is that it is designed to insert a gene into retinal cells so that they can produce their own supply of anti-VEGF fab indefinitely, ...