AMD, Choroidal Neovascularization, CNV, nAMD, Neovascular Age-related Macular Degeneration, Neovascular AMD, wAMD, Wet Age-related Macular Degeneration, Wet AMD
Conditions
Keywords
Age-Related Macular Degeneration, Neovascular Age-Related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration, Choroidal Neovascularization, Retinal Degeneration, Retinal Diseases, Eye Diseases, Ranibizumab, 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
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 or nAMD). 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 (anti-VEGF) therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to maintain or prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every 4 to 16 weeks in frequency, to maintain efficacy. Due to the burden of these treatments, patients often experience a decline in vision with reduced frequency of treatment over time.
Detailed description
This randomized, partially masked, active-controlled, Phase 2b/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 ABBV-RGX-314 relative to an active comparator. The primary endpoint of this study is the mean change from baseline in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to ranibizumab at Week 54. Approximately 630 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
AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)
BIOLOGICALRanibizumab (LUCENTIS®)
0.5 mg (0.05 mL of 10 mg/mL solution) administered by intravitreal injection approximately every 28 days
Sponsors
AbbVie
REGENXBIO Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The administration of ABBV-RGX-314 requires an outpatient surgical procedure performed in an operating room, while the active control, ranibizumab, 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 (ranibizumab)
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 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, as determined by CRC 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. History of intraocular surgery in the study eye within 12 weeks prior to randomization 7. 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 8. Prior treatment with gene therapy 9. Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
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 | Incidence of ocular AEs and any SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidences of ocular and overall AEs over 54 weeks | Through Week 54 | AEs over 54 weeks |
| Incidences of ocular and overall AEs over 98 weeks | Through Week 98 | AEs over 98 weeks |
| Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score | Week 98 | BCVA measured by ETDRS |
| Proportion of participants with worsened BCVA | Week 54; Week 98 | Proportion with worsened BCVA |
| Proportion of participants with improved BCVA | Week 54; Week 98 | Proportion with improved BCVA |
| Proportion of participants (1) gaining > 0 letters; (2) losing > 0 letters; maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA | Week 54; Week 98 | Proportion gaining or losing \> 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 injections (ABBV-RGX-314 randomized participants) | Week 54; Week 98 | 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 98 in BCVA (control arm participants who cross over to ABBV-RGX-314) | Week 54 to Week 98 | Mean change in BCVA based on ETDRS score |
| Mean change from baseline in CRT as measured by SD-OCT | Week 54; (ABBV-RGX-314 randomized participants) Week 98 | Mean change in CRT as measured by SD-OCT |
| Mean change from Week 54 to Week 98 in CRT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) | from Week 54 to Week 98 | Mean change in CRT as measured by SD-OCT |
| Mean change from baseline in CPT as measured by SD-OCT | Week 54; (ABBV-RGX-314 randomized participants) Week 98 | Mean change in CPT as measured by SD-OCT |
| Mean change from Week 54 to Week 98 in CPT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) | from Week 54 to Week 98 | Mean change in CPT as measured by SD-OCT |
| Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) | Through Week 98 | Mean number of supplemental anti-VEGF injections |
| Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314) | Through Week 98 | Proportion of participants with 0, 1, 2, and 3 supplemental injections |
| Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314) | Through Week 98 | Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections |
| Proportion of participants that received 1 or 2 injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314) | Through Week 98 | In the subset of participants who were given supplemental anti-VEGF injections, proportion of participants that received 1 or 2 injections |
| Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants) | Through Week 98 | Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate |
| Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants) | Through Week 98 | Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate |
| Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants) | Through Week 54 and Week 98 | Supplemental anti-VEGF injection annualized rate |
| Supplemental anti-VEGF injection annualized rate through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) | Through Week 54 and Week 98 | Supplemental anti-VEGF injection annualized rate |
| Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 98 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX-314) | After Week 58 through Week 98 | Percent reduction in anti-VEGF injection annualized rate |
| Supplemental anti-VEGF injection annualized rate after Week 58 through Week 98 (control arm participants who cross over to ABBV-RGX-314) | After Week 58 to Week 98 | Supplemental anti-VEGF injection annualized rate |
| Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants) | Week 98 | Time to first supplemental anti-VEGF injection |
| Time to first supplemental anti-VEGF injection after the Week 58 injection (control arm participants who cross over to ABBV-RGX-314) | After Week 58 to Week 98 | Time to first supplemental anti-VEGF injection |
| Mean change from baseline in NEI-VFQ-25 (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98 | Week 54; Week 98 | Mean change in NEI VGQ-25 (composite score) at week 54 (control arm participants who cross over to ABBV-RGX-314) |
| Mean change from baseline in MacTSQ (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98 | Week 54; Week 98 | Mean change from baseline in MacTSQ (composite score) at week 54 and (control arm participants who cross over to ABBV-RGX-314) at Week 98 |
| Aqueous ABBV-RGX-314 TP concentrations (ABBV-RGX-314 randomized participants) | Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98 | Aqueous ABBV-RGX-314 TP concentration |
| Aqueous ABBV-RGX-314 TP concentrations (control arm participants who cross over to ABBV-RGX-314) | Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98 | Aqueous ABBV-RGX-314 TP concentration |
| Immunogenicity measurements (ABBV-RGX-314 randomized participants) | Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98 | 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) | Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98 | 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 timepoints | Through Week 50 | BCVA measured by ETDRS |
| Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed timepoints | 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 Treatement Substudy: Mean number of supplemental anti-VEGF injections | Through Week 50 | Mean supplemental anti-VEGF injections |
| Bilateral Treatment Substudy: Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections | Through Week 50 | Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections |
| Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations | Wk 26, Wk 34, Wk 50 | Aqueous humor and serum ABBV-RGX-314 TP Concentrations |
| Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum anti-AAV8 antibodies) and enzyme-linked immunospot at assessed time points | Wk 18, Wk 34, Wk 50 | Immunogenicity measurements |
Countries
United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed