A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— FOCUS  

Official title:

Long-term Effects of Semaglutide on Diabetic Retinopathy in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03811561
• Other study ID #: NN9535-4352
• Secondary ID: U1111-1201-62562
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 8, 2019
• Est. completion date: November 7, 2027

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1500
• Est. completion date: November 7, 2027
• Est. primary completion date: December 25, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Semaglutide
Participants will get one dose of semaglutide once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).
• Placebo (semaglutide)
Participants will get one dose of placebo (semaglutide) once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Canada,  Czechia,  Germany,  Greece,  India,  Israel,  Latvia,  Mexico,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression.	Percentage of subjects (yes/no).	Year 5
Secondary	Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye.	Measured in months.	Up to 5 years
Secondary	Change in visual acuity in the worse seeing eye.	Measured in number of letters using the ETDRS protocol.	Week 0, Year 5
Secondary	Change in visual acuity in the better seeing eye.	Measured in number of letters using the ETDRS protocol.	Week 0, Year 5
Secondary	Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation.	Percentage of subjects (yes/no).	Week 0-Year 5
Secondary	Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation.	Percentage of subjects (yes/no).	Week 0-Year 5
Secondary	Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF).	Percentage of subjects (yes/no).	Week 0-Year 5
Secondary	Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid.	Percentage of subjects (yes/no).	Week 0-Year 5
Secondary	Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy.	Percentage of subjects (yes/no).	Week 0-Year 5
Secondary	Presence of at least 3 steps ETDRS subject level improvement.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of at least 2 steps ETDRS subject level progression.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of at least 2 steps ETDRS subject level improvement.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of persistent visual acuity up to 38 ETDRS letters in either eye.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline.	Percentage of subjects (yes/no).	Year 5
Secondary	Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline.	Percentage of subjects (yes/no).	Year 5
Secondary	Presence of ciDME in either eye.	Percentage of subjects (yes/no).	Year 5
Secondary	Change in glycosylated haemoglobin (HbA1c).	Measured in %-points.	Week 0, Year 5
Secondary	Change in body weight.	Measured in kg.	Week 0, Year 5
Secondary	Change in systolic and diastolic blood pressure.	Measured in mmHg.	Week 0, Year 5
Secondary	Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides.	Measured in mmol/L	Week 0, Year 5