Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD

Phase 3RecruitingNCT04704921

AbbVie630 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 50 YearsMax age: 89 Years

Medical Language ↔ Plain English

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 Exclusion Criteria (Bilateral Treatment Substudy)\*: 1. CNV or macular edema in either eye secondary to any causes other than AMD 2. Subfoveal fibrosis or atrophy in either eye 3. Any condition in the investigator's opinion that could limit VA improvement in either eye 4. Active or history of retinal detachment, or current retinal tear that cannot be treated in either eye 5. Advanced glaucoma or history of secondary glaucoma in either eye 6. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months 7. History of intraocular surgery in either eye within 12 weeks prior to randomization 8. History of intravitreal therapy in either eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening 9. Prior treatment with gene therapy (\*) For previously treated crossover participants, criteria apply to the eye not treated in the main study only.

Locations (89)

Retinal Research Institute /ID# 256019

Phoenix, Arizona, United States

RECRUITING

Barnet Dulaney Perkins Eye Center - Sun City /ID# 256055

Sun City, Arizona, United States

RECRUITING

University of Arkansas for Medical Sciences /ID# 271290

Little Rock, Arkansas, United States

RECRUITING

Retina Vitreous Assoc Med Grp /ID# 256299

Beverly Hills, California, United States

Outcomes

Primary Outcomes

Mean change from baseline in Best Corrected Visual Acuity (BCVA)

BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)

Time frame: At Week 54

Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs

Incidence of ocular AEs and any SAEs

Time frame: Week 50

Secondary Outcomes

Proportion of participants with ≤ 2 supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants)

Proportion of supplemental anti-VEGF injections.

Time frame: Through Week 54

Proportion of participants with no supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants)

Proportion of supplemental anti-VEGF injections.

Time frame: Through Week 54

Incidences of ocular and overall AEs over 54 weeks

AEs over 54 weeks

Time frame: Through Week 54

Incidences of ocular and overall AEs over 98 weeks

AEs over 98 weeks

Time frame: Through Week 98

Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score

BCVA measured by ETDRS

Time frame: Week 98

Proportion of participants with worsened BCVA

Proportion with worsened BCVA

Time frame: Week 54; Week 98

Proportion of participants with improved BCVA

Proportion with improved BCVA

Time frame: Week 54; Week 98

Proportion of participants (1) gaining > 0 letters; (2) losing > 0 letters; maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA

Proportion gaining or losing \> 0 letters based on ETDRS score; proportion maintaining vision

Time frame: Week 54; Week 98

Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injections (ABBV-RGX-314 randomized participants)

Mean change in BCVA based on ETDRS score for participants who received 0 or more supplemental anti-VEGF injection

Time frame: Week 54

Mean change from Week 54 to Week 98 in BCVA (control arm participants who cross over to ABBV-RGX-314)

Mean change in BCVA based on ETDRS score

Time frame: Week 54 to Week 98

Mean change from baseline in CRT as measured by SD-OCT

Mean change in CRT as measured by SD-OCT

Time frame: Week 54; (ABBV-RGX-314 randomized participants) Week 98

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)

Mean change in CRT as measured by SD-OCT

Time frame: from Week 54 to Week 98

Mean change from baseline in CPT as measured by SD-OCT

Mean change in CPT as measured by SD-OCT

Time frame: Week 54; (ABBV-RGX-314 randomized participants) Week 98

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)

Mean change in CPT as measured by SD-OCT

Time frame: from Week 54 to Week 98

Proportion of participants with a reduction in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants)

Proportion of participants with a reduction of in anti-VEGF injection annualized rate compared with the prior year

Time frame: Through Week 54 and Week 98

Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants)

Supplemental anti-VEGF injection annualized rate

Time frame: Through Week 54 and Week 98

Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms through Week 54 and Week 98

Supplemental anti-VEGF injection annualized rate

Time frame: Through Week 54 and Week 98

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)

Percent reduction in anti-VEGF injection annualized rate

Time frame: After Week 58 through Week 98

Supplemental anti-VEGF injection annualized rate after Week 58 through Week 98 (control arm participants who cross over to ABBV-RGX-314)

Supplemental anti-VEGF injection annualized rate

Time frame: After Week 58 to Week 98

22. Time to first supplemental anti-VEGF injection after the Week 2 injection in the ABBV-RGX-314 arms

Time to first supplemental anti-VEGF injection

Time frame: Week 98

Time to first supplemental anti-VEGF injection after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314

Time to first supplemental anti-VEGF injection

Time frame: After Week 58 to Week 98

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

Mean change in NEI VGQ-25 (composite score) at week 54 (control arm participants who cross over to ABBV-RGX-314)

Time frame: Week 54; Week 98

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

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

Time frame: Week 54; Week 98

Aqueous ABBV-RGX-314 TP concentrations (ABBV-RGX-314 randomized participants)

Aqueous ABBV-RGX-314 TP concentration

Time frame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98

Aqueous ABBV-RGX-314 TP concentrations (control arm participants who cross over to ABBV-RGX-314)

Aqueous ABBV-RGX-314 TP concentration

Time frame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98

Immunogenicity measurements (ABBV-RGX-314 randomized participants)

Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP)

Time frame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98

Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)

Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP)

Time frame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98

Bilateral Treatment Substudy: Incidence of nonocular AEs and any AEs of special interest

Nonocular AEs and AEs of Special interest

Time frame: Week 50

Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed timepoints

BCVA measured by ETDRS

Time frame: Through Week 50

Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed timepoints

Mean change in CRT as measured by SD-OCT

Time frame: Through Week 50

Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate

Supplemental anti-VEGF injection annualized rate

Time frame: Through Week 50

Bilateral Treatement Substudy: Mean number of supplemental anti-VEGF injections

Mean supplemental anti-VEGF injections

Time frame: Through Week 50

Bilateral Treatment Substudy: Proportion of participants with no supplemental anti-VEGF injections

Proportion of participants with no supplemental anti-VEGF injections

Time frame: Through Week 50

Bilateral Treatment Substudy: Proportion of particpants with ≤2 supplemental anti-VEGF injections

Proportion of participants with ≤2 supplemental anti-VEGF injections

Time frame: Through Week 50

Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations

Aqueous humor and serum ABBV-RGX-314 TP Concentrations

Time frame: Wk 26, Wk 34, Wk 50

Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum anti-AAV8 antibodies) and enzyme-linked immunospot at assessed time points

Immunogenicity measurements

Time frame: Wk 18, Wk 34, Wk 50

Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD

Overview

Conditions

Interventions

Eligibility

Locations (89)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts