Clinical trial NCT04429503: Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease
Official title: A Randomized, Double-Masked, Active-Controlled Phase 2/3 Study of the Efficacy and Safety of High-Dose Aflibercept in Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diabetic Macular Edema
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2020-06-12
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine if treatment with high-dose aflibercept (HD) at intervals of 12 or 16 weeks provides non-inferior best corrected visual acuity (BCVA) compared to aflibercept dosed every 8 weeks.

The secondary objectives of the study are as follows:

* To determine the effect of HD vs. aflibercept on anatomic and other visual measures of response
* To evaluate the safety, immunogenicity, and pharmacokinetics (PK) of aflibercept


Eligibility criteria: Key Inclusion Criteria:

* Diabetic macular edema (DME) with central involvement in the study eye
* Best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye with decreased vision determined to be primarily the result of DME
* Willing and able to comply with clinic visits and study-related procedures
* Provide informed consent signed by study participant or legally acceptable representative

Extension Phase: All randomized patients that complete visit 26, week 96, as long as the patient 1) provides informed consent and 2) no treatment for DME has been given in the study eye other than the randomized study treatment.

Key Exclusion Criteria:

* Evidence of macular edema due to any cause other than diabetes mellitus in either eye
* Active proliferative diabetic retinopathy in the study eye
* IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) or panretinal laser photocoagulation (PRP) /macular laser photocoagulation within 12 weeks (84 days) or intraocular or periocular corticosteroids within 16 weeks (112 days) of the screening visit in the study eye
* Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy, etc.) at any time
* Treatment with ocriplasmin (JETREA®) in the study eye at any time

NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Primary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants With BCVA ≥69 Letters at Week 48
timeFrame: At Week 48
measure: Percentage of Participants Without Fluid at Foveal Center at Week 48
timeFrame: At Week 48
measure: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48
timeFrame: At Week 48
measure: Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48
timeFrame: Baseline, Week 48
measure: Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48
timeFrame: Through Week 48
measure: Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA
timeFrame: Baseline, Week 48
measure: Change From 8-weeks Post Initial Treatment Phase in BCVA in the Study Eye in Participants With Both 8-weeks Post Initial Treatment Phase BCVA and Week 48 BCVA
timeFrame: Baseline, Week 48
measure: Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60
timeFrame: Baseline, Week 60
measure: Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96
timeFrame: Through Week 96
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96
timeFrame: Through Week 96
measure: Number of Participants With Any Serious TEAE Through Week 96
timeFrame: Through Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Regeneron Study Site
state: Arizona
city: Arcadia
country: United States
facility: Regeneron Study Site
state: California
city: Beverly Hills
country: United States
facility: Regeneron Study Site
state: California
city: Campbell
country: United States
facility: Regeneron Study Site
state: California
city: Encino
country: United States
facility: Regeneron Study Site
state: California
city: Fullerton
country: United States
facility: Regeneron Study Site
state: California
city: Huntington Beach
country: United States
facility: Regeneron Study Site
state: California
city: Long Beach
country: United States
facility: Regeneron Study Site
state: California
city: Palo Alto
country: United States
facility: Regeneron Study Site
state: California
city: Pasadena
country: United States
facility: Regeneron Study Site
state: California
city: Poway
country: United States
facility: Regeneron Study Site
state: California
city: Rancho Cordova
country: United States
facility: Regeneron Study Site
state: California
city: Riverside
country: United States
facility: Regeneron Study Site
state: California
city: Torrance
country: United States
facility: Regeneron Study Site
state: California
city: Colorado Springs
country: United States
facility: Regeneron Study Site
state: Colorado
city: Durango
country: United States
facility: Regeneron Study Site
state: Colorado
city: Lakewood
country: United States
facility: Regeneron Study Site
state: Colorado
city: Waterford
country: United States
facility: Regeneron Study Site
state: Connecticut
city: Clearwater
country: United States
facility: Regeneron Study Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Regeneron Study Site
state: Florida
city: Fort Myers
country: United States
facility: Regeneron Study Site
state: Florida
city: Jacksonville
country: United States
facility: Regeneron Study Site
state: Florida
city: Lakeland
country: United States
facility: Regeneron Study Site
state: Florida
city: Largo
country: United States
facility: Regeneron Study Site
state: Florida
city: Melbourne
country: United States
facility: Regeneron Study Site
state: Florida
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Orlando
country: United States
facility: Regeneron Study Site
state: Florida
city: Pinellas Park
country: United States
facility: Regeneron Study Site
state: Florida
city: Plantation
country: United States
facility: Regeneron Study Site
state: Florida
city: Saint Petersburg
country: United States
facility: Regeneron Study Site
state: Florida
city: Stuart
country: United States
facility: Regeneron Study Site
state: Florida
city: Winter Haven
country: United States
facility: Regeneron Study Site
state: Florida
city: Augusta
country: United States
facility: Regeneron Study Site
state: Georgia
city: Marietta
country: United States
facility: Regeneron Study Site 1
state: Georgia
city: Marietta
country: United States
facility: Regeneron Study Site 2
state: Georgia
city: 'Aiea
country: United States
facility: Regeneron Study Site
state: Hawaii
city: Oak Forest
country: United States
facility: Regeneron Study Site
state: Illinois
city: Springfield
country: United States
facility: Regeneron Study Site
state: Illinois
city: Springfield
country: United States
facility: Regeneron Study Site
state: Illinois
city: Carmel
country: United States
facility: Regeneron Study Site
state: Indiana
city: Shawnee Mission
country: United States
facility: Regeneron Study Site
state: Kansas
city: Baltimore
country: United States
facility: Regeneron Study Site
state: Maryland
city: Hagerstown
country: United States
facility: Regeneron Study Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Royal Oak
country: United States
facility: Regeneron Study Site
state: Michigan
city: Southaven
country: United States
facility: Regeneron Study Site
state: Mississippi
city: Henderson
country: United States
facility: Regeneron Study Site
state: Nevada
city: Bloomfield
country: United States
facility: Regeneron Study Site
state: New Jersey
city: Edison
country: United States
facility: Regeneron Study Site
state: New Jersey
city: Teaneck
country: United States
facility: Regeneron Study Site
state: New Jersey
city: Great Neck
country: United States
facility: Regeneron Study Site
state: New York
city: Liverpool
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: Oceanside
country: United States
facility: Regeneron Study Site
state: New York
city: Shirley
country: United States
facility: Regeneron Study Site
state: New York
city: Asheville
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Charlotte
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Beachwood
country: United States
facility: Regeneron Study Site
state: Ohio
city: Cincinnati
country: United States
facility: Regeneron Study Site
state: Ohio
city: Cincinnati
country: United States
facility: Regeneron Study Site
state: Ohio
city: Cleveland
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dublin
country: United States
facility: Regeneron Study Site
state: Ohio
city: Edmond
country: United States
facility: Regeneron Study Site
state: Oklahoma
city: Tulsa
country: United States
facility: Regeneron Study Site
state: Oklahoma
city: Portland
country: United States
facility: Regeneron Study Site
state: Oregon
city: Bethlehem
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Kingston
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Monroeville
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Beaufort
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Ladson
country: United States
facility: Regeneron Study Site
state: South Carolina
city: West Columbia
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Rapid City
country: United States
facility: Regeneron Study Site
state: South Dakota
city: Germantown
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Knoxville
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Nashville
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Abilene
country: United States
facility: Regeneron Study Site
state: Texas
city: Bellaire
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site 2
state: Texas
city: The Woodlands
country: United States
facility: Regeneron Study Site
state: Texas
city: Willow Park
country: United States
facility: Regeneron Study Site
state: Texas
city: Salt Lake City
country: United States
facility: Regeneron Study Site 1
state: Utah
city: Fairfax
country: United States
facility: Regeneron Study Site
state: Virginia
city: Norfolk
country: United States
facility: Regeneron Study Site
state: Virginia
city: Morgantown
country: United States
facility: Regeneron Study Site
state: West Virginia
city: Calgary
country: Canada
facility: Regeneron Study Site
state: Alberta
city: Mississauga
country: Canada
facility: Regeneron Study Site
state: Ontario
city: North York
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Sherbrooke
country: Canada
facility: Regeneron Study Site
state: Quebec
city: Pardubice
country: Czechia
facility: Regeneron Study Site
city: Prague 5
country: Czechia
facility: Regeneron Study Site
city: Praha 10
country: Czechia
facility: Regeneron Study Site
city: Praha 2
country: Czechia
facility: Regeneron Study Site
city: Neubrandenburg
country: Germany
facility: Regeneron Study Site
state: Mecklenburg-Westfalen
city: Gottingen
country: Germany
facility: Regeneron Study Site
state: Nordrhein-Westfalen
city: Munster
country: Germany
facility: Regeneron Study Site
state: Nordrhein-Westfalen
city: Pecs
country: Hungary
facility: Regeneron Study Site 1
state: Baranya
city: Szombathely
country: Hungary
facility: Regeneron Study Site
state: Vas
city: Zalaegerszeg
country: Hungary
facility: Regeneron Study Site
state: Zala Megye
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Debrecen
country: Hungary
facility: Regeneron Study Site
city: Szeged
country: Hungary
facility: Regeneron Study Site
city: Nagakute
country: Japan
facility: Regeneron Study Site
state: Aichi
city: Nagoya
country: Japan
facility: Regeneron Study Site
state: Aichi
city: Nagoya
country: Japan
facility: Regeneron Study Site
state: Aichi
city: Yoshida-Gun
country: Japan
facility: Regeneron Study Site
state: Fukui
city: Kurume
country: Japan
facility: Regeneron Study Site
state: Fukuoka
city: Koriyama
country: Japan
facility: Regeneron Study Site
state: Fukushima
city: Hakodate
country: Japan
facility: Regeneron Study Site
state: Hokkaido
city: Kobe
country: Japan
facility: Regeneron Study Site
state: Hyogo
city: Mito
country: Japan
facility: Regeneron Study Site
state: Ibaraki
city: Toride
country: Japan
facility: Regeneron Study Site
state: Ibaraki
city: Tsuchiura-shi
country: Japan
facility: Regeneron Study Site
state: Ibaraki
city: Kita-gun
country: Japan
facility: Regeneron Study Site
state: Kagawa
city: Kawasaki
country: Japan
facility: Regeneron Study Site
state: Kanagawa
city: Matsumoto
country: Japan
facility: Regeneron Study Site
state: Nagano
city: Nagasaki City
country: Japan
facility: Regeneron Study Site
state: Nagasaki
city: Kashihara
country: Japan
facility: Regeneron Study Site
state: Nara
city: Hirakata
country: Japan
facility: Regeneron Study Site
state: Osaka
city: Tokorozawa
country: Japan
facility: Regeneron Study Site
state: Saitama
city: Susono
country: Japan
facility: Regeneron Study Site
state: Shizuoka
city: Chiyoda-ku
country: Japan
facility: Regeneron Study Site
state: Tokyo
city: Hachioji
country: Japan
facility: Regeneron Study Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Regeneron Study Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Regeneron Study Site
state: Tokyo
city: Shimotsuke-shi
country: Japan
facility: Regeneron Study Site
state: Totigi
city: Ube
country: Japan
facility: Regeneron Study Site
state: Yamaguchi
city: Fukuoka
country: Japan
facility: Regeneron Study Site
city: Fukuoka
country: Japan
facility: Regeneron Study Site
city: Kagoshima
country: Japan
facility: Regeneron Study Site
city: Osaka
country: Japan
facility: Regeneron Study Site
city: Saitama
country: Japan
facility: Regeneron Study Site
city: Tokushima
country: Japan
facility: Regeneron Study Site
city: Arecibo
country: Puerto Rico
facility: Regeneron Study Site
city: Sunderland
country: United Kingdom
facility: Regeneron Study Site
state: Tyne And Wear
city: London
country: United Kingdom
facility: Regeneron Study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: