RGX-314 Gene Therapy for Diabetic Retinopathy

(ALTITUDE® Trial)

Recruiting at 45 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: REGENXBIO, Inc.

Must be taking: Anti-VEGF

Disqualifiers: Retinal detachment, Vitrectomy, 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: 12

Duration: 7 weeks

130 Participants Needed

Trial Summary

What is the purpose of this trial?

ABBV-RGX-314 is being developed as a novel, potential one-time gene therapy treatment for the treatment of Diabetic Retinopathy (DR) with and without Center-Involved Diabetic Macular Edema (CI-DME). DR is a chronic and progressive complication of diabetes mellitus. It is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that leads to further deterioration of functional vision. Despite the availability of current treatments, diabetic retinopathy remains the leading cause of vision loss in working-age adults, those between the ages of 20 and 74. Existing treatment with anti-VEGF agents, although shown to be effective, are limited by short therapeutic half-lives, which then require frequent intravitreal injections over the patient's lifetime, resulting in increased risk of associated adverse events and significant treatment burden. Due to the burden of treatment, patients often do not closely adhere to treatment regimens and experience sub-optimal outcomes and a decline in vision.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that anti-VEGF injections can be safely deferred for at least 6 months for some participants.

What data supports the effectiveness of the treatment RGX-314 for diabetic retinopathy?

Research on gene therapies, including RGX-314, shows promise in treating retinal diseases like age-related macular degeneration by delivering therapeutic genes to the eye. This suggests potential effectiveness for similar conditions like diabetic retinopathy, as these therapies aim to address underlying issues in the retina. ^{1 2 3 4 5}

Is RGX-314 gene therapy safe for humans?

Gene therapy using viral vectors, like those in RGX-314, has shown promising safety results in various clinical trials for eye conditions. While some trials reported mild inflammation that responded to treatment, no major safety concerns were noted, suggesting it is generally safe in humans. ^{6 7 8 9 10}

What makes the RGX-314 treatment unique for diabetic retinopathy?

RGX-314 is a gene therapy that uses adeno-associated viral vectors to deliver genetic material directly to the retina, which is different from traditional treatments that often involve repeated injections of medication. This approach aims to provide a long-term solution by addressing the underlying genetic causes of the condition. ^{1 4 11 12 13}

Eligibility Criteria

This trial is for adults aged 25-89 with diabetic retinopathy, who have good vision (20/40 or better) and can delay other treatments like PRP or anti-VEGF injections for at least 6 months. It's not for those with active macular edema, prior eye surgeries, potential pregnancy, or retinal issues not caused by diabetes.

Inclusion Criteria

Your vision in the study eye is 20/40 or better.

I am 25-89 years old with diabetic retinopathy and can delay certain treatments for 6 months.

It's okay if you have had a certain eye condition in the past in the eye being studied.

Exclusion Criteria

I have active diabetic macular edema.

I have had PRP or retinal laser treatment in my study eye.

My eye condition is not due to diabetic retinopathy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-RGX-314 gene therapy via a single suprachoroidal space injection, with some cohorts receiving a protocol-mandated steroid regimen

7 weeks

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Regular visits for assessment at Week 12, Week 24, Week 36, and Week 48

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Up to Week 82

Treatment Details

Interventions

• RGX-314

Trial Overview The study tests RGX-314 gene therapy as a one-time treatment for diabetic retinopathy. Participants will receive different doses of RGX-314 administered into the suprachoroidal space of the eye to see if it can improve their condition without frequent treatments.

Participant Groups

Group I: Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid Experimental Treatment 2 Interventions

ABBV-RGX-314 Dose 4 and Topical Steroid

Group II: Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid Experimental Treatment 2 Interventions

ABBV-RGX-314 Dose 3 and Topical Steroid

Group III: Part 1: ABBV-RGX-314 Treatment Arm (Dose 2) Experimental Treatment 1 Intervention

ABBV-RGX-314 Dose 2

Group IV: Part 1: ABBV-RGX-314 Treatment Arm (Dose 1) Experimental Treatment 1 Intervention

ABBV-RGX-314 Dose 1

Group V: Part 1: Observation Control Arm Active Control 1 Intervention

Observation Control

Group VI: Part 2: Aflibercept Control Active Control 1 Intervention

Control treatment arm

Who Is Running the Clinical Trial?

REGENXBIO, Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

Regenxbio Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

REGENXBIO Inc.

Industry Sponsor

Trials

25

Recruited

3,100+

Findings from Research

Retinal gene therapies, particularly for age-related macular degeneration (AMD), are showing promise in clinical trials, with five therapies (Luxturna, ADVM-022, RGX-314, GT-005, and HMR59) being evaluated for their effectiveness against this common condition.

These therapies could potentially provide long-lasting treatment with a single administration, significantly changing the treatment landscape for chronic retinal diseases and reducing the ongoing burden of care for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. Khanani, AM., Thomas, MJ., Aziz, AA., et al.[2023]

Gene therapy for neovascular age-related macular degeneration (nAMD) aims to provide a long-term solution by using adeno-associated virus (AAV) vectors to deliver anti-VEGF proteins, potentially reducing the need for frequent injections and improving visual outcomes.

Current research is focusing on optimizing gene delivery methods and exploring various therapeutic proteins, such as soluble fms-like tyrosine kinase-1 (sFLT-1) and other anti-angiogenic agents, to enhance the efficacy and safety of treatments for AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for age-related macular degeneration. Moore, NA., Bracha, P., Hussain, RM., et al.[2018]

In a follow-up phase 1 trial involving 11 patients aged 11-46 years, the subretinal injection of AAV2-hRPE65v2 into the contralateral eye showed no serious adverse events related to the treatment, indicating a favorable safety profile.

Most patients experienced significant improvements in mobility and light sensitivity in the newly treated eye, with effects lasting up to 3 years, demonstrating the efficacy of AAV2-hRPE65v2 as a gene therapy for inherited retinal dystrophy caused by RPE65 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Bennett, J., Wellman, J., Marshall, KA., et al.[2022]

The gene therapy rAAV.sFLT-1 was found to be safe and well tolerated in a phase 1 trial involving nine patients with wet age-related macular degeneration, with no drug-related adverse events reported.

A significant portion of the treatment group (67%) did not require any rescue injections after the therapy, suggesting that a single subretinal injection could provide long-term benefits compared to the frequent injections currently needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Rakoczy, EP., Lai, CM., Magno, AL., et al.[2022]

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Gene therapy in the second eye of RPE65-deficient dogs improves retinal function. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Late presentation of RPE65 retinopathy in three siblings. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Practical considerations of recombinant adeno-associated virus-mediated gene transfer for treatment of retinal degenerations. [2012]

5. England pubmed.ncbi.nlm.nih.gov

Gene therapy for age-related macular degeneration. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Clinical applications of retinal gene therapy. [2023]

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

Development of a translatable gene augmentation therapy for CNGB1-retinitis pigmentosa. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. [2022]

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

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Clinical applications of retinal gene therapies. [2022]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Adeno-associated viral vectors for retinal gene transfer and treatment of retinal diseases. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Versatility of AAV vectors for retinal gene transfer. [2021]