Clinical trial NCT04704921: Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD
Official title: A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: AMD
nAMD
Wet Age-related Macular Degeneration
wAMD
Wet AMD
CNV
Neovascular AMD
Neovascular Age-related Macular Degeneration
Choroidal Neovascularization
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: REGENXBIO Inc.
First posted: 2021-01-12
Enrollment: 540
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 ABBV-RGX-314 treatment arms, 1 control arm (ranibizumab)
Primary purpose: TREATMENT

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 540 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

Eligibility criteria: 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

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

Primary outcomes:
measure: Mean change from baseline in Best Corrected Visual Acuity (BCVA)
timeFrame: At Week 54
Secondary outcomes:
measure: Proportion of participants with ≤ 2 supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants)
timeFrame: Through Week 54
measure: Proportion of participants with no supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants)
timeFrame: Through Week 54
measure: Percent reduction in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)
timeFrame: Through Week 54
measure: Mean change from Baseline in BCVA
timeFrame: Week 54
measure: Incidences of ocular and overall AEs over 54 weeks
timeFrame: Through Week 54
measure: Incidences of ocular and overall AEs over 98 weeks
timeFrame: Through Week 98
measure: Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score
timeFrame: Week 98
measure: Proportion of participants with worsened BCVA
timeFrame: Week 54; Week 98
measure: Proportion of participants with improved BCVA
timeFrame: Week 54; Week 98
measure: Proportion of participants (1) gaining or losing > 0 letters; (2) maintaining vision (compared with baseline as per BCVA)
timeFrame: Week 54; Week 98
measure: Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injections (ABBV-RGX-314 randomized participants)
timeFrame: Week 54
measure: Mean change from Week 54 to Week 98 in BCVA (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Week 54 to Week 98
measure: Mean change from baseline in CRT as measured by SD-OCT
timeFrame: Week 54; (ABBV-RGX-314 randomized participants) Week 98
measure: 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)
timeFrame: from Week 54 to Week 98
measure: Mean change from baseline in CPT as measured by SD-OCT
timeFrame: Week 54; (ABBV-RGX-314 randomized participants) Week 98
measure: 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)
timeFrame: from Week 54 to Week 98
measure: 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)
timeFrame: Through Week 54 and Week 98
measure: Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants)
timeFrame: Week 98
measure: Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms through Week 54 and Week 98
timeFrame: Through Week 54 and Week 98
measure: 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)
timeFrame: After Week 58 through Week 98
measure: Supplemental anti-VEGF injection annualized rate after Week 58 through Week 98 (control arm participants who cross over to ABBV-RGX-314)
timeFrame: After Week 58 to Week 98
measure: Time to first supplemental anti-VEGF injection after the Week 2 injection in the ABBV-RGX-314 arms
timeFrame: Week 98
measure: Time to first supplemental anti-VEGF injection after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314
timeFrame: After Week 58 to Week 98
measure: 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
timeFrame: Week 54; Week 98
measure: 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
timeFrame: Week 54; Week 98
measure: Aqueous ABBV-RGX-314 TP concentrations (ABBV-RGX-314 randomized participants)
timeFrame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98
measure: Aqueous ABBV-RGX-314 TP concentrations (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98
measure: Immunogenicity measurements (ABBV-RGX-314 randomized participants)
timeFrame: Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98
measure: Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 118-Retinal Consultants of Arizona, Ltd.
state: Arizona
city: Sun City
country: United States
facility: 170-Barnet Dulaney Perkins Eye Center
state: Arizona
city: Little Rock
country: United States
facility: 292-Univ of Arkansas Medical Sciences Jones Eye Institute
state: Arkansas
city: Beverly Hills
country: United States
facility: 133-Retina-Vitreous Associates Medical Group
state: California
city: Campbell
country: United States
facility: 142-Retinal Diagnostic Center
state: California
city: Encino
country: United States
facility: 160-The Retina Partners - Encino
state: California
city: Fullerton
country: United States
facility: 150-Retina Consultants of Orange County - Fullerton Office
state: California
city: Huntington Beach
country: United States
facility: 284- Salehi Retina Institute
state: California
city: Irvine
country: United States
facility: 193-University of California Irvine - School of Medicine - The Gavin Herbert Eye Institute
state: California
city: Los Angeles
country: United States
facility: 187-Doheny Eye Institute - Doheny Eye Center
state: California
city: Mountain View
country: United States
facility: 132-Northern California Retina Vitreous Associates Medical Group, Inc. - Mountain View Office
state: California
city: Pasadena
country: United States
facility: UCLA Doheny Eye Center
state: California
city: Pasadena
country: United States
facility: 185-California Eye Specialists Medical Group Inc. - Pasadena
state: California
city: Poway
country: United States
facility: 121-Retina Consultants San Diego
state: California
city: Sacramento
country: United States
facility: 163-Retina Consultants
state: California
city: San Francisco
country: United States
facility: 190-West Coast Retina Medical Group - San Francisco Office
state: California
city: San Francisco
country: United States
facility: 137-UCSF Medical Center - Retina and Vitreous Clinic
state: California
city: Santa Ana
country: United States
facility: 182-Orange County Retina Medical Group
state: California
city: Santa Barbara
country: United States
facility: 114-California Retina Consultants
state: California
city: Colorado Springs
country: United States
facility: 177-Retina Consultants of Southern Colorado PC- Colorado Springs
state: Colorado
city: Durango
country: United States
facility: 141-Southwest Retina Consultants
state: Colorado
city: Lakewood
country: United States
facility: 188-Colorado Retina Associates (CRA) - Red Rocks Medical Center Location
state: Colorado
city: Waterford
country: United States
facility: 180-Retina Group of New England - New London
state: Connecticut
city: Deerfield Beach
country: United States
facility: 199-Advanced Research, LLC
state: Florida
city: Gainesville
country: United States
facility: 148-Vitreo Retinal Associates PA - The Millennium Center
state: Florida
city: Lakeland
country: United States
facility: 205-Florida Retina Consultants - Lakeland
state: Florida
city: Miami
country: United States
facility: 181-Bascom Palmer Eye Institute - University of Miami Health System
state: Florida
city: Pensacola
country: United States
facility: 152-Retina Specialty Institute - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: 165-Retina Vitreous Associates of Florida (RVA) - Saint Petersburg
state: Florida
city: Tallahassee
country: United States
facility: 278-Southern Vitreoretinal Associates, P.L.
state: Florida
city: Augusta
country: United States
facility: 122-Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: 145-Georgia Retina PC - Marietta
state: Georgia
city: Marietta
country: United States
facility: 295-Marietta Eye Clinic
state: Georgia
city: Sandy Springs
country: United States
facility: 297- Thomas Eye Group
state: Georgia
city: 'Aiea
country: United States
facility: 164 Retina Consultants of Hawaii (RCH) - Pali Momi Medical Center Location
state: Hawaii
city: Chicago
country: United States
facility: 151-Illinois Eye and Ear Infirmary at UI Health UIC
state: Illinois
city: Lemont
country: United States
facility: 183-University Retina and Macula Associates, P.C. - Lemont Office
state: Illinois
city: Oak Forest
country: United States
facility: 184-University Retina and Macula Associates, PC - Oak Forest
state: Illinois
city: Springfield
country: United States
facility: 226-Springfield Clinic
state: Illinois
city: Indianapolis
country: United States
facility: 162-Midwest Eye Institute
state: Indiana
city: New Albany
country: United States
facility: 174-John-Kenyon American Eye Institute - New Albany
state: Indiana
city: Lenexa
country: United States
facility: 186-Retina Associates, P.A. - Shawnee Mission
state: Kansas
city: Metairie
country: United States
facility: 294-Retina Associates - New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: 288 Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: 146-The Retina Care Center, LLC
state: Maryland
city: Baltimore
country: United States
facility: 108-The Johns Hopkins Hospital - Wilmer Eye Institute - East Baltimore
state: Maryland
city: Chevy Chase
country: United States
facility: 192 - The Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: 149-Cumberland Valley Retina Consultants (CVRC)
state: Maryland
city: Boston
country: United States
facility: 106-Ophthalmic Consultants of Boston, Inc.
state: Massachusetts
city: Grand Blanc
country: United States
facility: 257-Retina Associates of Michigan - Grand Blanc Office
state: Michigan
city: Royal Oak
country: United States
facility: 153-Associated Retinal Consultants P.C.
state: Michigan
city: Minneapolis
country: United States
facility: 155-VitreoRetinal Surgery, PA - Edina Location
state: Minnesota
city: Rochester
country: United States
facility: 166-Mayo Clinic - Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: 291-The Retina Institute
state: Missouri
city: Reno
country: United States
facility: 119- Sierra Eye Associates
state: Nevada
city: Albuquerque
country: United States
facility: 125-Eye Associates of New Mexico - Albuquerque - Retina Center Location
state: New Mexico
city: Great Neck
country: United States
facility: 124-Long Island Vitreoretinal Consultants - Great Neck
state: New York
city: Liverpool
country: United States
facility: 289- Retina Vitreous Surgeons of Central NY Syracuse
state: New York
city: Durham
country: United States
facility: 131-Duke Eye Center - Erwin Road - Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: 283-Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: 138-Cincinnati Eye Institute - Blue Ash
state: Ohio
city: Cleveland
country: United States
facility: 167-Retina Associates of Cleveland, Inc
state: Ohio
city: Cleveland
country: United States
facility: 173-Cleveland Clinic
state: Ohio
city: Edmond
country: United States
facility: 175-Retina Vitreous Center (RVC)
state: Oklahoma
city: Eugene
country: United States
facility: 290- Verum Research, LLC
state: Oregon
city: Portland
country: United States
facility: 143-Retina Northwest, PC
state: Oregon
city: Erie
country: United States
facility: 252-Erie Retinal Surgery, Inc
state: Pennsylvania
city: Monroeville
country: United States
facility: 287-Retina Vitreous Consultants - Monroeville
state: Pennsylvania
city: Philadelphia
country: United States
facility: 105 Mid Atlantic Retina - Philadelphia
state: Pennsylvania
city: Ladson
country: United States
facility: 210-Charleston Neuroscience Institute
state: South Carolina
city: Rapid City
country: United States
facility: 156-Black Hills Regional Eye Institute
state: South Dakota
city: Germantown
country: United States
facility: 109-Charles Retina Institute
state: Tennessee
city: Abilene
country: United States
facility: 144-West Texas Retina Consultants (WTRC) - Abilene Location
state: Texas
city: Austin
country: United States
facility: 168-Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: 147-Retina Consultants of Austin
state: Texas
city: Austin
country: United States
facility: 157-Austin Clinical Research, LLC
state: Texas
city: Beaumont
country: United States
facility: 293-Retina Consultants of Texas - Beaumont, TX
state: Texas
city: Bellaire
country: United States
facility: 286-Retina and Vitreous of TX PLLC
state: Texas
city: Burleson
country: United States
facility: 189-Baylor Scott & White Surgicare
state: Texas
city: Dallas
country: United States
facility: 139-Texas Retina Associates
state: Texas
city: Fort Worth
country: United States
facility: 279 Star Vision Consultants
state: Texas
city: San Antonio
country: United States
facility: 237-Retina Associates of South Texas, PA - San Antonio
state: Texas
city: San Antonio
country: United States
facility: 268-Retinal Consultants of San Antonio (RCSA) - Medical Center
state: Texas
city: Southlake
country: United States
facility: 172-Retina Center of Texas - Southlake
state: Texas
city: The Woodlands
country: United States
facility: 117-Retina Consultants of Texas - The Woodlands
state: Texas
city: Salt Lake City
country: United States
facility: 161-Retina Associates of Utah, PC
state: Utah
city: Salt Lake City
country: United States
facility: 176-John A. Moran Eye Center - University of Utah Health Care
state: Utah
city: Norfolk
country: United States
facility: 140 Wagner Macula & Retina Center - Norfolk, VA Office
state: Virginia
city: Bellevue
country: United States
facility: 253-Pacific Northwest Retina
state: Washington
city: Silverdale
country: United States
facility: 262-Retina Center Northwest - Silverdale
state: Washington
city: Madison
country: United States
facility: 154-University of Wisconsin Health - University Station Clinic
state: Wisconsin
Study officials:
References: