AMD, nAMD, Wet Age-related Macular Degeneration, wAMD, WetAMD, CNV
Conditions
Keywords
Age-Related Macular Degeneration, Neovascular Age-Related Macular Degeneration, Wet Macular Degeneration, Choroidal Neovascularization, Retinal Degeneration, Retinal Diseases, Eye Diseases, Ranibizumab, Aflibercept, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Antineoplastic Agents, Gene Therapy, Anti-vascular endothelial grown factory therapy, Anti-VEGF therapy, Macular Degeneration
Brief summary
ABBV-RGX-314 (also known as RGX-314) is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-vascular endothelial growth factor (VEGF) therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. ABBV-RGX-314 is being developed as a potential one-time treatment for wet AMD.
Detailed description
This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to aflibercept. Approximately 660 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms. A bilateral treatment substudy conducted at US sites is an open-label, partially randomized, parallel arm study to evaluate the safety and efficacy of subretinal ABBV-RGX-314 administered bilaterally in participants who have bilateral nAMD. Previously treated crossover participants from the control arm of the main study who crossed over and received ABBV-RGX-314 in the study eye will receive the same ABBV-RGX-314 dose in the contralateral eye (ie, same dose as in the study eye), and newcomers (participants who have not been randomized in an ABBV-RGX-314 study) and untreated crossover participants (ongoing control participants in the main study who have completed Week 54 but have not crossed over to receive ABBV-RGX-314 in the main study) will be randomized in a 2:1 ratio to receive ABBV-RGX-314 Dose 1 or ABBV-RGX-314 Dose 2 in both eyes. Up to 15 participants who qualify for the substudy will be enrolled and followed for a minimum of 50 weeks.
Interventions
GENETICABBV-RGX-314 Dose 1
AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
GENETICABBV-RGX-314 Dose 2
AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)
BIOLOGICALAflibercept (EYLEA®)
2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections
Sponsors
REGENXBIO Inc.
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
ABBV-RGX-314 administration is performed as an outpatient surgical procedure in an operating room, while the active control, aflibercept, is administered via intravitreal injection in an office setting. This study will be partially masked which will include masking of key study assessors and study drug dose.
Intervention model description
2 ABBV-RGX-314 treatment arms, 1 control arm (aflibercept)
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 50 years and ≤ 89 years 2. An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye 3. Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in the study eye previously treated with anti-VEGF 4. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye 5. Willing and able to provide written, signed informed consent for this study 6. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry Inclusion Criteria (Bilateral Treatment Substudy)\*: 1. An ETDRS BCVA letter score between ≤ 83 and ≥ 40 in both eyes 2. Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in both eyes 3. Must be pseudophakic (at least 12 weeks postcataract surgery) in both eyes 4. Willing and able to provide written, signed informed consent for this study 5. Newcomers must have active disease in the study eye; crossover participants must have active disease in the eye not treated in the main study
Exclusion criteria
1. CNV or macular edema in the study eye secondary to any causes other than AMD 2. Subfoveal fibrosis or atrophy in the study eye 3. Any condition in the investigator's opinion that could limit VA improvement in the study eye 4. Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye 5. Advanced glaucoma or history of secondary glaucoma in the study eye 6. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 7. History of intraocular surgery in the study eye within 12 weeks prior to randomization 8. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1 9. Prior treatment with gene therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in Best Corrected Visual Acuity (BCVA) | At Week 54 | BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS) |
| Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs | Week 50 | AEs and SAEs through Week 50 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidences of ocular and overall SAEs over 54 weeks | Through Week 54 | AEs over 54 weeks |
| Proportion of participants with worsened BCVA | Week 54 | Proportion with worsened BCVA |
| Proportion of participants with improved BCVA | Week 54 | Proportion with improved BCVA |
| Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA | Week 54 | Proportion gaining or losing greater than 0 letters based on ETDRS score; proportion maintaining vision |
| Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injection (ABBV-RGX-314 randomized participants) | Week 54 | Mean change in BCVA based on ETDRS score for participants who received 0 or more supplemental anti-VEGF injection |
| Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314) | Week 54 to Week 108 | Mean change in BCVA based on ETDRS score |
| Mean change from baseline in central retinal thickness (CRT) as measured by SD-OCT | Week 54 | Mean change in CRT as measured by SD-OCT |
| Mean change from Week 54 to Week 108 in CRT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) | Week 54 to Week 108 | Mean change in CRT as measured by SD-OCT |
| Mean change from baseline in center point thickness (CPT) as measured by SD-OCT | Week 54 | Mean change in CPT as measured by SD-OCT |
| Mean change from Week 54 to Week 108 in CPT, as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) | Week 54 to Week 108 | Mean change in CPT as measured by SD-OCT |
| Proportion of participants with a reduction in anti-VEGF injection annualized rate | Through Week 54 | Proportion of participants with a reduction in anti-VEGF injection annualized rate compared with the prior year |
| Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms | Through Week 54 | Supplemental anti-VEGF injection annualized rate |
| Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 108 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX 314) | After Week 58 to Week 108 | Percent reduction in anti-VEGF injection annualized rate |
| Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314) | After Week 58 through Week 108 | Supplemental anti-VEGF injection annualized rate |
| Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants) | Through Week 54 | Time to first supplemental anti-VEGF injection |
| Time to first supplemental anti-VEGF injection after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314 | After Week 58 through Week 108 | Time to first supplemental anti-VEGF injection |
| Proportion of participants with ≤ 2 supplemental anti-VEGF injections | Through Week 54 (ABBV-RGX-314 randomized participants only) | Proportion of supplemental anti-VEGF injections |
| Mean change from baseline in MacTSQ (composite score) | Week 54 and Week 108 | Mean change from baseline in MacTSQ (composite score) at week 54 and (control arm participants who cross over to ABBV-RGX-314) at Week 108 |
| Aqueous ABBV-RGX-314 transgene product (TP) concentration (ABBV-RGX-314 randomized participants) | Week -2, Week 14, Week 38, and Week 54 | Aqueous ABBV-RGX-314 TP concentration |
| Aqueous ABBV-RGX-314 TP concentration (control arm participants who cross over to ABBV-RGX-314) | Week 54, Week 74, Week 90, and Week 108 | Aqueous ABBV-RGX-314 TP concentration |
| Serum ABBV-RGX-314 TP concentrations (at select sites) | Week -2, Week 14, Week 38, and Week 54 | Serum ABBV-RGX-314 TP concentration |
| Immunogenicity measurements (ABBV-RGX-314 randomized participants) | Week -2, Week 14, Week 38, and Week 54 | Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP) |
| Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314) | Week 54, Week 74, Week 90, and Week 108 | Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP) |
| Bilateral Treatment Substudy: Incidence of nonocular AEs and any AEs of special interest | Week 50 | Nonocular AEs and AEs of Special Interest |
| Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed time points | Through Week 50 | BCVA measured by ETDRS |
| Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed time points | Through Week 50 | Mean change in CRT as measured by SD-OCT |
| Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate | Through Week 50 | Supplemental anti-VEGF injection annualized rate |
| Bilateral Treatment Substudy: Mean number of supplemental anti-VEGF injections | Through Week 50 | Mean supplemental anti-VEGF injections |
| Bilateral Treatment Substudy: Proportion of participants with no supplemental anti-VEGF injections | Through Week 50 | Proportion of participants with no supplemental anti-VEGF injections |
| Bilateral Treatment Substudy: Proportion of participants with ≤ 2 supplemental anti-VEGF injections | Through Week 50 | Proportion of participants with ≤ 2 supplemental anti-VEGF injections |
| Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations | Week 26, Week 34, Week 50 | Aqueous humor and serum ABBV-RGX-314 TP concentrations |
| Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum antiAAV8 antibodies) and enzyme-linked immunospot at assessed time points | Week 18, Week 34, Week 50 | Immunogenicity measurements |
| Mean change from baseline in NEI VFQ-25 (composite score) | Week 54 and Week 108 | Mean change in NEI VFQ-25 (composite score) at Week 54 and (control arm participants who cross over to ABBV-RGX-314) Week 108 |
| Proportion of participants with no supplemental anti-VEGF injections | Through Week 54 (ABBV-RGX-314 randomized participants only) | Proportion of supplemental anti-VEGF injections |
Countries
Canada, France, Germany, Hungary, Italy, Japan, Puerto Rico, Spain, United Kingdom, United States
Contacts
Primary ContactPatient Advocacy
Outcome results
None listed