Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease

Type 2 Diabetes Mellitus Clinical Trial

— PHOTON  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04429503
• Other study ID #: VGFTe-HD-DME-1934
• Secondary ID: 2019-003643-30
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: June 29, 2020
• Est. completion date: June 29, 2024

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 660
• Est. completion date: June 29, 2024
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Diabetic Macular Edema
• Macular Edema
• Type 1 Diabetes Mellitus
• Type 2 Diabetes Mellitus

Intervention

Drug:
• aflibercept
Intravitreally (IVT) administered as a liquid formulation in a vial
• High-dose aflibercept
Intravitreally (IVT) administered as a liquid formulation in a vial

Locations

Country	Name	City	State
Canada	Regeneron Study Site	Calgary	Alberta
Canada	Regeneron Study Site	Mississauga	Ontario
Canada	Regeneron Study Site	North York	Ontario
Canada	Regeneron Study Site	Sherbrooke	Quebec
Czechia	Regeneron Study Site	Pardubice
Czechia	Regeneron Study Site	Prague 5
Czechia	Regeneron Study Site	Praha 10
Czechia	Regeneron Study Site	Praha 2
Germany	Regeneron Study Site	Gottingen	Nordrhein-Westfalen
Germany	Regeneron Study Site	Munster	Nordrhein-Westfalen
Germany	Regeneron Study Site	Neubrandenburg	Mecklenburg-Westfalen
Hungary	Regeneron Study Site	Budapest
Hungary	Regeneron Study Site	Budapest
Hungary	Regeneron Study Site	Budapest
Hungary	Regeneron Study Site	Budapest
Hungary	Regeneron Study Site	Debrecen
Hungary	Regeneron Study Site 1	Pecs	Baranya
Hungary	Regeneron Study Site	Szeged
Hungary	Regeneron Study Site	Szombathely	Vas
Hungary	Regeneron Study Site	Zalaegerszeg	Zala Megye
Japan	Regeneron Study Site	Chiyoda-ku	Tokyo
Japan	Regeneron Study Site	Fukuoka
Japan	Regeneron Study Site	Fukuoka
Japan	Regeneron Study Site	Hachioji	Tokyo
Japan	Regeneron Study Site	Hakodate	Hokkaido
Japan	Regeneron Study Site	Hirakata	Osaka
Japan	Regeneron Study Site	Itabashi-ku	Tokyo
Japan	Regeneron Study Site	Kagoshima
Japan	Regeneron Study Site	Kashihara	Nara
Japan	Regeneron Study Site	Kawasaki	Kanagawa
Japan	Regeneron Study Site	Kita-gun	Kagawa
Japan	Regeneron Study Site	Kobe	Hyogo
Japan	Regeneron Study Site	Koriyama	Fukushima
Japan	Regeneron Study Site	Kurume	Fukuoka
Japan	Regeneron Study Site	Matsumoto	Nagano
Japan	Regeneron Study Site	Meguro-ku	Tokyo
Japan	Regeneron Study Site	Mito	Ibaraki
Japan	Regeneron Study Site	Nagakute	Aichi
Japan	Regeneron Study Site	Nagasaki City	Nagasaki
Japan	Regeneron Study Site	Nagoya	Aichi
Japan	Regeneron Study Site	Nagoya	Aichi
Japan	Regeneron Study Site	Osaka
Japan	Regeneron Study Site	Saitama
Japan	Regeneron Study Site	Shimotsuke-shi	Totigi
Japan	Regeneron Study Site	Susono	Shizuoka
Japan	Regeneron Study Site	Tokorozawa	Saitama
Japan	Regeneron Study Site	Tokushima
Japan	Regeneron Study Site	Toride	Ibaraki
Japan	Regeneron Study Site	Tsuchiura-shi	Ibaraki
Japan	Regeneron Study Site	Ube	Yamaguchi
Japan	Regeneron Study Site	Yoshida-Gun	Fukui
Puerto Rico	Regeneron Study Site	Arecibo
United Kingdom	Regeneron Study Site	London
United Kingdom	Regeneron Study Site	Sunderland	Tyne And Wear
United States	Regeneron Study Site	'Aiea	Hawaii
United States	Regeneron Study Site	Abilene	Texas
United States	Regeneron Study Site	Arcadia	California
United States	Regeneron Study Site	Asheville	North Carolina
United States	Regeneron Study Site	Augusta	Georgia
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Beachwood	Ohio
United States	Regeneron Study Site	Beaufort	South Carolina
United States	Regeneron Study Site	Bellaire	Texas
United States	Regeneron Study Site	Bethlehem	Pennsylvania
United States	Regeneron Study Site	Beverly Hills	California
United States	Regeneron Study Site	Bloomfield	New Jersey
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Campbell	California
United States	Regeneron Study Site	Carmel	Indiana
United States	Regeneron Study Site	Charlotte	North Carolina
United States	Regeneron Study Site	Cincinnati	Ohio
United States	Regeneron Study Site	Cincinnati	Ohio
United States	Regeneron Study Site	Clearwater	Florida
United States	Regeneron Study Site	Cleveland	Ohio
United States	Regeneron Study Site	Colorado Springs	Colorado
United States	Regeneron Study Site	Dublin	Ohio
United States	Regeneron Study Site	Durango	Colorado
United States	Regeneron Study Site	Edison	New Jersey
United States	Regeneron Study Site	Edmond	Oklahoma
United States	Regeneron Study Site	Encino	California
United States	Regeneron Study Site	Fairfax	Virginia
United States	Regeneron Study Site	Fort Lauderdale	Florida
United States	Regeneron Study Site	Fort Myers	Florida
United States	Regeneron Study Site	Fullerton	California
United States	Regeneron Study Site	Germantown	Tennessee
United States	Regeneron Study Site	Great Neck	New York
United States	Regeneron Study Site	Hagerstown	Maryland
United States	Regeneron Study Site	Henderson	Nevada
United States	Regeneron Study Site	Huntington Beach	California
United States	Regeneron Study Site	Jacksonville	Florida
United States	Regeneron Study Site	Kingston	Pennsylvania
United States	Regeneron Study Site	Knoxville	Tennessee
United States	Regeneron Study Site	Ladson	South Carolina
United States	Regeneron Study Site	Lakeland	Florida
United States	Regeneron Study Site	Lakewood	Colorado
United States	Regeneron Study Site	Largo	Florida
United States	Regeneron Study Site	Liverpool	New York
United States	Regeneron Study Site	Long Beach	California
United States	Regeneron Study Site 1	Marietta	Georgia
United States	Regeneron Study Site 2	Marietta	Georgia
United States	Regeneron Study Site	Melbourne	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Monroeville	Pennsylvania
United States	Regeneron Study Site	Morgantown	West Virginia
United States	Regeneron Study Site	Nashville	Tennessee
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Norfolk	Virginia
United States	Regeneron Study Site	Oak Forest	Illinois
United States	Regeneron Study Site	Oceanside	New York
United States	Regeneron Study Site	Orlando	Florida
United States	Regeneron Study Site	Palo Alto	California
United States	Regeneron Study Site	Pasadena	California
United States	Regeneron Study Site	Phoenix	Arizona
United States	Regeneron Study Site	Pinellas Park	Florida
United States	Regeneron Study Site	Plantation	Florida
United States	Regeneron Study Site	Portland	Oregon
United States	Regeneron Study Site	Poway	California
United States	Regeneron Study Site	Rancho Cordova	California
United States	Regeneron Study Site	Rapid City	South Dakota
United States	Regeneron Study Site	Riverside	California
United States	Regeneron Study Site	Royal Oak	Michigan
United States	Regeneron Study Site	Saint Petersburg	Florida
United States	Regeneron Study Site 1	Salt Lake City	Utah
United States	Regeneron Study Site 2	San Antonio	Texas
United States	Regeneron Study Site	Shawnee Mission	Kansas
United States	Regeneron Study Site	Shirley	New York
United States	Regeneron Study Site	Southaven	Mississippi
United States	Regeneron Study Site	Springfield	Illinois
United States	Regeneron Study Site	Springfield	Illinois
United States	Regeneron Study Site	Stuart	Florida
United States	Regeneron Study Site	Teaneck	New Jersey
United States	Regeneron Study Site	The Woodlands	Texas
United States	Regeneron Study Site	Torrance	California
United States	Regeneron Study Site	Tulsa	Oklahoma
United States	Regeneron Study Site	Waterford	Connecticut
United States	Regeneron Study Site	West Columbia	South Carolina
United States	Regeneron Study Site	Willow Park	Texas
United States	Regeneron Study Site	Winter Haven	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Bayer

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Hungary,  Japan,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).	Baseline, Week 48
Secondary	Percentage of Participants With a =2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48	The DRSS was assessed according to the following scale: 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.	Baseline, Week 48
Secondary	Percentage of Participants Gaining =15 Letters in BCVA From Baseline at Week 48	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best). Only one study eye per participant was analyzed within the study	Baseline, Week 48
Secondary	Percentage of Participants With BCVA =69 Letters at Week 48	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).	At Week 48
Secondary	Percentage of Participants Without Fluid at Foveal Center at Week 48	Retinal fluid status was evaluated using spectral domain optical coherence tomography (SD-OCT) on the study eye.	At Week 48
Secondary	Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48	Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).	Baseline, Week 48
Secondary	Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48	Leakage is the release of fluorescein dye from diseased retinal vessels.	At Week 48
Secondary	Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48	Vision-specific quality of life is assessed with the NEI VFQ-25 (National Eye Institute Visual Function Questionnaire), i.e. a 25-item questionnaire that gives a score on a scale from 0 (worst) to 100 (best = no vision problems).	Baseline, Week 48
Secondary	Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48	Concentrations of Free Aflibercept in Plasma by Time and Treatment Group	Through Week 48
Secondary	Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best). (Per Statistical Analysis Plan (SAP) Version 2.0 Appendix 10.9 for US Only)	Baseline, Week 48
Secondary	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	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best). (Per SAP Version 2.0 Appendix 10.9 for US Only)	Baseline, Week 48
Secondary	Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60	Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).	Baseline, Week 60
Secondary	Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96	Number of participants with pre-existing immunoreactivity and treatment-emergent ADA response reported	Through Week 96
Secondary	Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96	A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.	Through Week 96
Secondary	Number of Participants With Any Serious TEAE Through Week 96	A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.	Through Week 96