Study of the Effects of High Dose Aflibercept Injected Into the Eye of Patients With an Age-related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye

Neovascular Age-Related Macular Degeneration Clinical Trial

— PULSAR  

Official title:

Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of High Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04423718
• Other study ID #: 20968
• Secondary ID: 2019-003851-12
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 11, 2020
• Est. completion date: August 12, 2024

Study information

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

Clinical Trial Summary

In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood into the light sensitive lining inside the eye (retina). The fluid buildup causes the central part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken (edema), which distorts vision.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1011
• Est. completion date: August 12, 2024
• Est. primary completion date: July 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye.

• Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye.

• BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye.

• Decrease in BCVA determined to be primarily the result of nAMD in the study eye.

• Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT.

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies.

• Other protocol-specified inclusion criteria.

Additional inclusion criteria for Year 3:

• At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92).

• Participant is enrolled at a site that participates in the extension period.

Exclusion Criteria:

• Causes of CNV other than nAMD in the study eye.

• Scar, fibrosis, or atrophy involving the central subfield in the study eye.

• Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye.

• Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye.

• History of idiopathic or autoimmune uveitis in the study eye.

• Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery.

• History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye.

• Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization.

• Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg).

• Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins.

• Other protocol-specified exclusion criteria

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
Solution in Vial, intravitreal (IVT) injection
• Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)
Solution in Vial, 2 mg, intravitreal (IVT) injection

Locations

Country	Name	City	State
Argentina	OFTALMOS, Instituto Oftalmologico de Alta Complejidad	Buenos Aires	Ciudad Auton. De Buenos Aires
Argentina	Organizacion Medica de Investigacion (OMI)	Buenos Aires	Ciudad Auton. De Buenos Aires
Australia	Eyeclinic Albury Wodonga	Albury	New South Wales
Australia	Hobart Eye Surgeons	Hobart	Tasmania
Australia	Marsden Eye Surgery Center	Parramatta
Australia	Sydney Retina Clinic	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt	Kärnten
Austria	Kepler Universitätsklinikum Campus III	Linz	Oberösterreich
Austria	Konventhospital Barmherzige Brüder Linz	Linz	Oberösterreich
Austria	Hanusch-Krankenhaus Wien	Wien
Bulgaria	Multiprofile Hospital for Active Treatment Sveta Sofia | Internal Diseases Department	Sofia
Bulgaria	SEHAT Pentagram	Sofia
Bulgaria	Spec. Hosp. for Active Treatment for Eye Diseases Zrenie	Sofia
Bulgaria	Specialized Hospital For Active Treatment of Eye Diseases Zora	Sofia
Bulgaria	UMHAT Alexandrovska EAD	Sofia
Bulgaria	Sveta Petka Eye Hospital	Varna
Canada	Institut de l'Oeil des Laurentides	Boisbriand	Quebec
Canada	St.Joseph's Health Care-London	London	Ontario
Canada	Toronto Retina Institute	Toronto	Ontario
China	Beijing Aier Intech Eye Hospital Co. LTD - Ophthalmology	Beijing
China	Beijing Hospital	Beijing
China	Beijing Tongren Hospital, Capital Medical University (East)	Beijing
China	Peking University People's Hospital	Beijing
China	Eye Center of the second Bethune Hospital, jinlin University	Changchun	Jilin
China	Aier Eye Hospital (Chengdu)	Chengdu	Sichuan
China	Chongqing Aier Ophthalmology Hospital	Chongqing
China	The 1st Affiliated Hospital Fujian Medical University	Fuzhou	Fujian
China	Guangzhou Aier Eye Hospital	Guangzhou	Guangdong
China	The 1st Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	ZheJiang Provincial People's Hospital	Hangzhou	Zhejiang
China	The Second Hospital of Anhui medical university	Hefei	Anhui
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of NanChang University	Nanchang	Jiangxi
China	Shanghai General Hospital	Shanghai
China	Shanghai Tongji Hospital of Tongji University	Shanghai
China	Shenyang He Eye Hospital	Shenyang	Liaoning
China	Shijiazhuang General Hospital	Shijiazhuang	Hebei
China	TianJin eye hospital	Tianjin
China	Tianjin Medical University Eye Hospital	Tianjin
China	Tianjin Medical University General Hospital	Tianjin
China	Tonghua Central Hospital	Tonghua	Jilin
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	The Affiliated Eye Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.	Wuhan	Hubei
China	Union Hospt Tongji Medical Colleg. Huazhong univ. Scien&Tech	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Hebei Eye Hospital	Xingtai	Hebei
China	The First People's Hospital of Xuzhou	Xuzhou	Jiangsu
China	The People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia
China	Henan Provincial Ophthalmology Hospital (Henan Eye Institute	Zhengzhou	Henan
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Plzen - Lochotin	Plzen-Lochotin
Czechia	Charles University in Prague	Prague
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Lexum a.s., Evropska ocni klinika	Praha 4
Czechia	AXON Clinical s.r.o.	Praha 5
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
France	Centre d'Ophtalmologie - Paradis-Monticelli	Marseille
France	Hôpital Lariboisière - Paris	Paris
France	Centre ophtalmologique Saint-Exupéry	Saint-Cyr-Sur-Loire
Georgia	LTD "Clinic LJ"	Kutaisi
Georgia	JSC "Evex Hospitals'	Tbilisi
Georgia	LTD "Chichua Medical Center MZERA"	Tbilisi
Georgia	LTD "Innova"	Tbilisi
Hungary	Budapest Retina Associates	Budapest
Hungary	Szent-Gyorgyi Albert Orvostudomanyi Egyetem	Szeged
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Assuta Medical Centers - HaShalom	Tel Aviv
Italy	A.O.U. di Cagliari	Cagliari	Sardegna
Italy	ASST Fatebenefratelli Sacco	Milano	Lombardia
Italy	Ospedale San Raffaele s.r.l.	Milano	Lombardia
Italy	A.O. di Perugia	Perugia	Umbria
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio
Italy	Fondazione PTV Policlinico Tor Vergata	Roma	Lazio
Italy	IRCCS Fondazione G.B. Bietti Studio e Ricerca in Otalmologia	Roma	Lazio
Japan	Akita University Hospital	Akita
Japan	Hyogo Prefectural Amagasaki General Medical Center	Amagasaki	Hyogo
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
Japan	University of Yamanashi Hospital	Chuo	Yamanashi
Japan	St.Luke's International Hospital	Chuoku	Tokyo
Japan	Nishikasai Inouye Eye Hospital	Edogawa-ku	Tokyo
Japan	Hayashi Eye Hospital	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Tokyo Medical University Hachioji Medical Center	Hachioji	Tokyo
Japan	Kansai Medical University Hospital	Hirakata	Osaka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Daiyukai Daiichi Hospital	Ichinomiya	Aichi
Japan	Tokiwadai Muranaka Eye Clinic	Itabashi-ku	Tokyo
Japan	Kanazawa Medical University Hospital	Kahoku-gun	Ishikawa
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	Medical corporation Eiwakai Dannoue Ophthalmology clinic	Kawasaki	Kanagawa
Japan	St. Marianna University Hospital	Kawasaki	Kanagawa
Japan	Kagawa University Hospital	Kita-gun	Kagawa
Japan	Kokura Memorial Hospital	Kitakyushu	Fukuoka
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Southern Tohoku Eye Clinic	Koriyama	Fukushima
Japan	Kurashiki Medical Center	Kurashiki	Okayama
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Shinshu University Hospital	Matsumoto	Nagano
Japan	National Hospital Organization Tokyo Medical Center	Meguro-ku	Tokyo
Japan	Kozawa Eye Hospital and Diabetes Center	Mito	Ibaraki
Japan	University of Miyazaki Hospital	Miyazaki
Japan	Kansai Medical University Medical Center	Moriguchi	Osaka
Japan	Aichi Medical University Hospital	Nagakute	Aichi
Japan	Japanese Red Cross Nagasaki Genbaku Hospital	Nagasaki
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	University of the Ryukyus Hospital	Nakagami	Okinawa
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Japanese Red Cross Saitama Hospital	Saitama
Japan	KKR Sapporo Medical Center	Sapporo	Hokkaido
Japan	Sapporo City General Hospital	Sapporo	Hokkaido
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Tokushima University Hospital	Tokushima
Japan	Mie University Hospital	Tsu	Mie
Japan	Yamaguchi University Hospital	Ube	Yamaguchi
Japan	Japanese Red Cross Wakayama Medical center	Wakayama
Japan	Yamagata University Hospital	Yamagata
Japan	Otakeganka Tsukimino Clinic	Yamato	Kanagawa
Japan	Oita University Hospital	Yufu	Oita
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Retina Center Nune Eye Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Latvia	Department of Ophthalmology	Riga
Latvia	Latvian American Eye Center	Riga
Latvia	Riga East Clinical University Hospital "Gailezers"	Riga
Lithuania	Hospital of LT University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	PI Klaipedos University Hospital	Klaipeda
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Portugal	AIBILI	Coimbra
Portugal	Espaco Medico de Coimbra	Coimbra
Portugal	ALM Oftalmolaser - Oftalmologia Medica e Cirurgica	Lisbon	Lisboa
Portugal	Centro Hospitalar Universitario do Porto	Porto
Portugal	Centro Hospitalar Vila Nova de Gaia/Espinho | Unit 1 - Clinical Research Office	Porto
Russian Federation	FBSI IRTC Eye Microsurgery n.a. acad. S.N. Fyodorov	Moscow
Russian Federation	Scientific Research Institution of Ophthalmic Diseases	Moscow
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical hospital center Zvezdara	Belgrade
Serbia	Klinicki centar Vojvodine	Novi Sad
Singapore	National University Hospital	Singapore
Singapore	Singapore National Eye Centre	Singapore
Slovakia	Fakultna nemocnica Nitra	Nitra
Slovakia	Nemocnica s Poliklinikou Trebisov, Svet zdravia a.s.	Trebisov
Slovakia	Fakultna nemocnica Trencin	Trencin
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Zilina
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau | Gynecology Department	Barcelona
Spain	Hospital Reina Sofía	Córdoba
Spain	Instituto Oftalmológico Francisco Gomez Ulla	Santiago de Compostela	A Coruña
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Spain	Hospital Miguel Servet	Zaragoza
Switzerland	Berner Augenklinik am Lindenhofspital	Bern
Switzerland	RétinElysée	Lausanne	Vaud
Switzerland	Stadtspital Triemli	Zürich
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital at Linkou	Taoyuan
Ukraine	Private enterprise private production company " Acinus"	Kropyvnytskyi
Ukraine	Centralna Polyclinica MVS Ukraiiny	Kyiv
Ukraine	Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi	Poltava
United States	Retina Consultants of Hawaii	'Aiea	Hawaii
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	Austin Retina Associates	Austin	Texas
United States	Retina Care Center	Baltimore	Maryland
United States	Mid Atlantic Retina	Bethlehem	Pennsylvania
United States	Retina Center of New Jersey	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Charleston Neuroscience Center	Charleston	South Carolina
United States	Retina Consultants of Southern Colorado, PC	Colorado Springs	Colorado
United States	Rand Eye Institute	Deerfield Beach	Florida
United States	Midwest Retina - Main Office	Dublin	Ohio
United States	Vitreo Retinal Surgery PA	Edina	Minnesota
United States	NJ Retina	Edison	New Jersey
United States	Retina Associates IL	Elmhurst	Illinois
United States	Erie Retinal Surgery, Inc.	Erie	Pennsylvania
United States	Retina Group of Florida	Fort Lauderdale	Florida
United States	Texas Retina Associates	Fort Worth	Texas
United States	Retina Consultants of Orange County	Fullerton	California
United States	Vitreo-Retinal Associates	Gainesville	Florida
United States	Long Island Vitreoretinal Consultants	Great Neck	New York
United States	Long Island Vitreoretinal Consultants - Hauppauge	Hauppauge	New York
United States	Florida Retina Institute	Jacksonville	Florida
United States	Eye Care Specialists	Kingston	Pennsylvania
United States	University of California San Diego	La Jolla	California
United States	Retina Consultants of Nevada	Las Vegas	Nevada
United States	Ophthalmic Consultants of Long Island	Lynbrook	New York
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	Florida Eye Associates	Melbourne	Florida
United States	Charles Retina Institute	Memphis	Tennessee
United States	Retina Macula Specialists of Miami	Miami	Florida
United States	West Virginia University	Morgantown	West Virginia
United States	Northern California Retina-Vitreous Associates	Mountain View	California
United States	Vanderbilt University Medical School	Nashville	Tennessee
United States	New England Retina Associates	New London	Connecticut
United States	University Retina and Macula Associates	Oak Forest	Illinois
United States	Florida Retina Institute	Orlando	Florida
United States	California Eye Specialists	Pasadena	California
United States	Retina Specialists	Pensacola	Florida
United States	Arizona Retina and Vitreous Consultants - Research	Phoenix	Arizona
United States	Retina Northwest, PC	Portland	Oregon
United States	Retina Consultants San Diego	Poway	California
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Consultants of Southern California	Redlands	California
United States	Kaiser Permanente Riverside Medical Center	Riverside	California
United States	Retina Vitreous Associates of Florida - Saint Petersburg	Saint Petersburg	Florida
United States	Retina Consultants, LLC	Salem	Oregon
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of Texas - San Antonio	San Antonio	Texas
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Southern Vitreoretinal Associates	Tallahassee	Florida
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Retina Consultants of Texas - The Woodlands	The Woodlands	Texas
United States	Ophthalmic Consultants of the Capital Region	Troy	New York
United States	Palmetto Retina Center, LLC	West Columbia	South Carolina
United States	Wolfe Eye Clinic, PC	West Des Moines	Iowa
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Bulgaria,  Canada,  China,  Czechia,  Estonia,  France,  Georgia,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Portugal,  Russian Federation,  Serbia,  Singapore,  Slovakia,  Spain,  Switzerland,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48	Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).	At baseline and Week 48
Secondary	Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60	Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).	At baseline and Week 60
Secondary	Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16		At Week 16
Secondary	Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48		At baseline and Week 48
Secondary	Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48		At Week 48
Secondary	Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48		At baseline and Week 48
Secondary	Change in Total Lesion Area From Baseline to Week 48		At baseline and Week 48
Secondary	Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48		At Week 48
Secondary	Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48		At baseline and Week 48
Secondary	Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48	NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)	At baseline and Week 48
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)		Up to 156 weeks
Secondary	Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48		Up to Week 48
Secondary	Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study		Up to week 96

External Links

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