Clinical trial NCT03811561: A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes
Official title: Long-term Effects of Semaglutide on Diabetic Retinopathy in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 1500
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: This study will look at the long-term effects of semaglutide (active medicine) on diabetic eye disease when compared to placebo (dummy medicine). The study will be performed in people with type 2 diabetes. Participants will either get semaglutide or placebo in addition to their diabetes medicines - which treatment the participant gets is decided by chance. Participants will inject the study medicine using a pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last for 5 years.


Eligibility criteria: Inclusion Criteria:

* Male or female, age greater than or equal to 18 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus.
* HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive).
* Eye inclusion criteria (both eyes must meet all criteria):
* Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by central reading centre
* No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema six months prior to the day of screening.
* No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema within three months after randomisation.
* Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS visual acuity protocol
* No previous treatment with pan-retinal laser photocoagulation
* No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema progression during the trial
* No substantial media opacities that would preclude successful imaging

Exclusion Criteria:

* Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
* Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
* Subjects presently classified as being in New York Heart Association (NYHA) Class IV
* Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR less than 30 ml/min/1.73 m\^2
* Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
* Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods
* Concurrent treatment with any GLP-1 receptor agonist or DPP-4 inhibitor from randomisation.
* Receipt of any investigational medicinal product within 30 days before screening
* Previous participation in this trial. Participation is defined as randomisation
* Known or suspected hypersensitivity to trial products or related products
* Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

Primary outcomes:
measure: Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression.
timeFrame: Year 5
Secondary outcomes:
measure: Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye.
timeFrame: Up to 5 years
measure: Change in visual acuity in the worse seeing eye.
timeFrame: Week 0, Year 5
measure: Change in visual acuity in the better seeing eye.
timeFrame: Week 0, Year 5
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation.
timeFrame: Week 0-Year 5
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation.
timeFrame: Week 0-Year 5
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF).
timeFrame: Week 0-Year 5
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid.
timeFrame: Week 0-Year 5
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy.
timeFrame: Week 0-Year 5
measure: Presence of at least 3 steps ETDRS subject level improvement.
timeFrame: Year 5
measure: Presence of at least 2 steps ETDRS subject level progression.
timeFrame: Year 5
measure: Presence of at least 2 steps ETDRS subject level improvement.
timeFrame: Year 5
measure: Presence of persistent visual acuity up to 38 ETDRS letters in either eye.
timeFrame: Year 5
measure: Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline.
timeFrame: Year 5
measure: Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline.
timeFrame: Year 5
measure: Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline.
timeFrame: Year 5
measure: Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline.
timeFrame: Year 5
measure: Presence of ciDME in either eye.
timeFrame: Year 5
measure: Change in glycosylated haemoglobin (HbA1c).
timeFrame: Week 0, Year 5
measure: Change in body weight.
timeFrame: Week 0, Year 5
measure: Change in systolic and diastolic blood pressure.
timeFrame: Week 0, Year 5
measure: Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides.
timeFrame: Week 0, Year 5
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Coronado
country: United States
facility: Southern California Res Ctr
state: California
city: Costa Mesa
country: United States
facility: FDRC
state: California
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Mgmt & Res Ctr
state: California
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Inst
state: California
city: Lomita
country: United States
facility: Torrance Clin Res Inst, Inc.
state: California
city: Los Angeles
country: United States
facility: Downtown LA Res Ctr. Inc.
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Research
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research_Sacramento_0
state: California
city: Ventura
country: United States
facility: Coastal Metabolic Research Center
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: Aurora
country: United States
facility: Rocky Mount Reg VA Med-DN
state: Colorado
city: Waterbury
country: United States
facility: Chase Medical Research LLC
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of W FL
state: Florida
city: Jacksonville
country: United States
facility: Est Cst Inst for Rsrch,Jksnvil
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Roswell
country: United States
facility: Endo Res Solutions Inc
state: Georgia
city: Chicago
country: United States
facility: Apex Medical Research Inc
state: Illinois
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Avon
country: United States
facility: American Health Network of Indiana, LLC_Avon
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Diab & Endo Res Center
state: Iowa
city: Lexington
country: United States
facility: Kentucky Diabetes-Endocrinology Center
state: Kentucky
city: Lexington
country: United States
facility: The Research Group of Lexington LLC
state: Kentucky
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research Inc
state: Kentucky
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center_Cary
state: Massachusetts
city: Boston
country: United States
facility: Joslin Center For Diabetes
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: NYC Research, Inc.
state: New York
city: Asheville
country: United States
facility: Mountain Diabetes & Endocrine Center
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Oklahoma City
country: United States
facility: Harold Hamm Diabetes Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Tristar Clin Investigations, PC
state: Pennsylvania
city: Bristol
country: United States
facility: Holston Medical Group Pc
state: Tennessee
city: Chattanooga
country: United States
facility: Univ Diab & Endo Consultants
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Diab Obes Clin Tri
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Austin
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Res-Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Med Cntr
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: San Antonio
country: United States
facility: VIP Trials
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Sugar Land
country: United States
facility: Simcare Medical Research, LLC
state: Texas
city: Spokane
country: United States
facility: MultiCare Inst for Res & Innov
state: Washington
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Ltda
state: Sao Paulo
city: Pleven
country: Bulgaria
facility: DCC I- Pleven EOOD
city: Pleven
country: Bulgaria
facility: MHAT Sveti Pantaleimon - Pleven, Internal Diseases
city: Plovdiv
country: Bulgaria
facility: MHAT "Med Line Clinic"
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi", Clinic of Endocr. and Metab. Diseases
city: Plovdiv
country: Bulgaria
facility: MHAT MC-Sv Ivan Rilski EOOD
city: Sofia
country: Bulgaria
facility: "DCC VII - Sofia", Endocrinology Consulting Room
city: Sofia
country: Bulgaria
facility: MHAT "Knyaginya Klementina" -Sofia EAD
city: Sofia
country: Bulgaria
facility: USHATE "Akad. Ivan Penchev" Second Clinic of Endocrinology
city: Sofia
country: Bulgaria
facility: "Fourth MHAT-Sofia EAD"
city: Sofia
country: Bulgaria
facility: "DCC XX - Sofia" EOOD, Endocrinology Consulting Room
city: Sofia
country: Bulgaria
facility: Medical centre Vitclinic EOOD
city: Edmonton
country: Canada
facility: Alberta Diabetes Institute
state: Alberta
city: Concord
country: Canada
facility: LMC Clinical Res Thornhill
state: Ontario
city: Etobicoke
country: Canada
facility: LMC Endo Ctr (Etobicoke) Ltd
state: Ontario
city: Toronto
country: Canada
facility: LMC Endo Centres Ltd.(Bayview)
state: Ontario
city: Pointe-Claire
country: Canada
facility: Centricity Res Pointe-Claire
state: Quebec
city: Saint-Laurent
country: Canada
facility: LMC Clin Rsrch Inc. (Montreal)
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 10
country: Czechia
facility: Diabetologie Krupska
city: Praha 4
country: Czechia
facility: Institut klinicke a experimentalni mediciny
city: Praha 4
country: Czechia
facility: MUDr. Michala Pelikanova
city: Praha
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady_Praha
city: Friedrichsthal
country: Germany
facility: Praxis Denger/Pfitzner, Friedrichsthal
city: Hamburg
country: Germany
facility: Diabetes-Zentrum-Wilhelmsburg GbR
city: Hamburg
country: Germany
facility: Wendisch/Dahl Hamburg (DZHW)
city: Hamburg
country: Germany
facility: Wendisch/Dahl Hamburg
city: Münster
country: Germany
facility: Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
city: Münster
country: Germany
facility: MedicalCenter am Clemenshospital - Schwerpunktpraxis für Diabetologie und Ernährungsmedizin
city: Rehlingen-Siersburg
country: Germany
facility: Praxis Dr. med. Wenzl-Bauer
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Zentrum für klinische Studien Alexander Segner
city: Athens
country: Greece
facility: University Hospital of Athens ATTIKON
state: Attica
city: Athens
country: Greece
facility: Iatriko Psychicou Private Clinic
city: Athens
country: Greece
facility: "Laiko" General Hospital of Athens
city: Athens
country: Greece
facility: "Laiko" General Hospital of Athens
city: Athens
country: Greece
facility: Iatriko Athinon 'Palaiou Falirou'
city: Haidari-Athens
country: Greece
facility: University Hospital of Athens ATTIKON
city: Thessaloniki
country: Greece
facility: "Ippokrateio" G.H. of Thessaloniki
city: Thessaloniki
country: Greece
facility: "Thermi" Private Hosital
city: Thessaloniki
country: Greece
facility: "Thermi" Private Hosital
city: Guntur
country: India
facility: Endolife Specialty Hospitals
state: Andhra Pradesh
city: Bangalore
country: India
facility: Narayana Hrudayalya Institute of Cardiac Sciences
state: Karnataka
city: Bangalore
country: India
facility: Diacon Hospital Private Limited
state: Karnataka
city: Kochi
country: India
facility: Amrita Institute Of Medical Sciences & Research Centre
state: Kerala
city: Thiruvananthapuram
country: India
facility: Indian Institute of Diabetes
state: Kerala
city: Mumbai
country: India
facility: BYL Nair Hospital and T N Medical College Department of endo
state: Maharashtra
city: Nagpur
country: India
facility: Government Medical College and Super Speciality Hospital, Nagpur
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Ansari Nagar, New Delhi 110029
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Delhi
country: India
facility: Apollo Hospital
state: New Delhi
city: Delhi
country: India
facility: Indraprastha Apollo Hospital
state: New Delhi
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Ludhiana
country: India
facility: Christian Medical College and Hospital
state: Punjab
city: Chennai
country: India
facility: Madras Diabetes Research Foundation
state: Tamil Nadu
city: Madurai
country: India
facility: Arthur Asirvatham hospital,
state: Tamil Nadu
city: Kolkata
country: India
facility: Apollo Gleneagles Hospital
state: West Bengal
city: Hyderabad
country: India
facility: Care Hospital
city: Haifa
country: Israel
facility: Diabetes and obesity center of excellence, Rambam MC
city: Jerusalem
country: Israel
facility: Diabetes Unit Hadassah Ein Karem MC
city: Kfar Saba
country: Israel
facility: Clinical Research Unit Meir Medical Center
city: Petah-Tikva
country: Israel
facility: Rabin MC Beilinson Campus Endo
city: Tel Hashomer
country: Israel
facility: Endrocrinolgy Clinic - Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Institute of Endocrinology, metabolism and hypertension
city: Jelgava
country: Latvia
facility: Zemgales diabetes centre
city: Ogre
country: Latvia
facility: Teterovska practice
city: Riga
country: Latvia
facility: Medical Centre Pulss 5
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Juglas Medicine Center
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Nutricion - Unidad de Inv de Enf Metab
state: México, D.F.
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González_Monterrey
state: Nuevo León
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
state: Podlaskie Voivodeship
city: Lodz
country: Poland
facility: Santa Sp. z o.o, Santa Familia Centrum Badan, Profilaktyki i Leczenia
state: Wojewodztwo Lodzkie
city: Bydgoszcz
country: Poland
facility: In-Vivo Sp. z o.o.
city: Chorzow
country: Poland
facility: B_Serwis Popenda Sp.J.
city: Gdansk
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdansku
city: Gdansk
country: Poland
facility: NZOZ Gdanska Poradnia Cukrzycowa Sp.z o.o.
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Kraków
country: Poland
facility: FutureMeds Sp. z o.o.
city: Lodz
country: Poland
facility: Santa Sp. z o.o, Santa Familia Centrum Badan, Profilaktyki i Leczenia
city: Lodz
country: Poland
facility: Prywatny Gabinet Lekarski Jan Ruxer
city: Poznan
country: Poland
facility: NZOZ "DiabMed" Poradnia Diabetologiczna
city: Poznan
country: Poland
facility: Gaja Poradnie Lekarskie
city: Zabrze
country: Poland
facility: SPSK nr 1 im. prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach, ul. 3-go Maja 13/15 41-800 Zabrze
city: Senhora Da Hora, Matosinhos
country: Portugal
facility: Unidade Local De Saude De Matosinhos E.P.E.
state: Matosinhos
city: Almada
country: Portugal
facility: Unidade Local De Saude De Almada-Seixal E.P.E.
city: Aveiro
country: Portugal
facility: Unidade Local De Saude Da Regiao De Aveiro E.P.E.
city: Coimbra
country: Portugal
facility: Unidade Local de Saúde de Coimbra, E.P.E.
city: Guimarães
country: Portugal
facility: Unidade Local de Saude do Alto Ave, E.P.E.
city: Lisboa
country: Portugal
facility: APDP - Associação Protectora dos Diabéticos de Portugal
city: Porto
country: Portugal
facility: Centro Hospitalar de São João
city: Porto
country: Portugal
facility: Unidade Local de Saude de Sao Joao E.P.E
city: Setubal
country: Portugal
facility: Unidade Local de Saúde da Arrábida, E.P.E.
city: Bucharest
country: Romania
facility: Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila
state: Bucurestii
city: Cluj Napoca
country: Romania
facility: Clinic of Diabetes Cluj
state: Cluj
city: Timisoara
country: Romania
facility: 3rd Clinic for Nutrition-Spitalulul Județean de Urgenta
state: Timis
city: Bucharest
country: Romania
facility: "Carol Davila" Military Emergency Hospital
city: Bucharest
country: Romania
facility: Sana Monitoring SRL
city: Bucharest
country: Romania
facility: SC Clinica Diabnutrimed S.R.L.
city: Barnaul
country: Russian Federation
facility: Multispecialty Medical Clinic Anturium LLC
city: Kazan
country: Russian Federation
facility: Kazan Federal University
city: Kazan
country: Russian Federation
facility: PIH "Clin Hosp "RZD-Medicina" former Kazan OJSC Rus Railways
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Endocrinology
city: Saint-Petersburg
country: Russian Federation
facility: City Consultative & Diagnostic Centre #1
city: Saint-Petersburg
country: Russian Federation
facility: Diagnistic Centre "Energo"
city: Saint-Petersburg
country: Russian Federation
facility: Consultative & Diagnostic Center with a Outpatient Hospital
city: Saratov
country: Russian Federation
facility: SHI Saratov City Clinical Hospital #9
city: Saratov
country: Russian Federation
facility: Regional clinical cardiology dispensary
city: Belgrade
country: Serbia
facility: CHC Zvezdara, Clinical department for endocrinology
city: Belgrade
country: Serbia
facility: Endocrinology, Diabetes and Metabolism Diseases Clinic
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Nis
country: Serbia
facility: Clinical Centre Nis, Endocrinology, Diabetes and Metabolism
city: Bratislava
country: Slovakia
facility: Nemocnica akademika L. Derera, UNB
city: Zilina
country: Slovakia
facility: Diabetologicka ambulancia, Dia Zilina s.r.o.
city: Zilina
country: Slovakia
facility: Medivasa s.r.o., Diabetologicka ambulancia
city: Zilina
country: Slovakia
facility: MEDIVASA, s.r.o., Diabetologicka ambulancia
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena
city: Valencia
country: Spain
facility: Hospital La Fe - Endocrinología y Nutrición
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: North Yorkshire
city: Nottingham
country: United Kingdom
facility: University Hospital, Queens Medical Centre
state: Nottinghamshire
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital - Clinical Research Unit
state: Somerset
city: London
country: United Kingdom
facility: Kings College Hospital
city: Norfolk
country: United Kingdom
facility: The Norfolk and Norwich University Hospital
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital NHS Trust
city: Somerset
country: United Kingdom
facility: Clinical Research Unit
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital (Treliske)
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: