Clinical trial NCT05259033: A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Semaglutide (COMBINE 2)
Official title: A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Semaglutide, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With a GLP 1 Receptor Agonist. COMBINE 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2022-02-28
Enrollment: 683
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 compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes.

The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide.

Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries.

Participants will get IcoSema or semaglutide, which they must inject once a week with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach.

The study will last for about 1 year and 1 month. Participants will have 18 clinic visits, 34 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls.

At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.


Eligibility criteria: Inclusion Criteria:

* Male or female and age above or equal to 18 years at the time of signing informed consent.
* Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
* HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
* Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
* Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above.
* Body mass index (BMI) below or equal to 40.0 kg/m\^2.

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
* Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
* Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening.
* Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
* Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
* Chronic heart failure classified as being in New York Heart Association Class IV at screening.
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for non dilated examination

Primary outcomes:
measure: Change From Baseline in Glycosylated Haemoglobin (HbA1c)
timeFrame: Baseline (week 0), (week 52)
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline (week 0), (week 52)
measure: Change From Baseline in Body Weight
timeFrame: Baseline (week 0), (week 52)
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3)
timeFrame: Week 0 to Week 57
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)
timeFrame: Week 0 to Week 57
measure: Number of Severe Hypoglycaemic Episodes (Level 3)
timeFrame: Week 0 to Week 57
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of AL at Birmingham_BRM
state: Alabama
city: Gilbert
country: United States
facility: Pri Med Grp dba/Gil Ctr Fam
state: Arizona
city: Sun City West
country: United States
facility: Clinical Research Institute of Arizona
state: Arizona
city: Concord
country: United States
facility: John Muir Physicians Network
state: California
city: Los Angeles
country: United States
facility: Velocity Clin Res Wstlke
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Toluca Lake
country: United States
facility: Premier Medical Center, Inc.
state: California
city: Fleming Island
country: United States
facility: Northeast Research Institute
state: Florida
city: Jacksonville
country: United States
facility: Northeast Res Inst. Inc.
state: Florida
city: Jacksonville
country: United States
facility: Est Cst Inst for Rsrch,Jksnvil
state: Florida
city: Miramar
country: United States
facility: South Broward Research LLC
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County, Inc.
state: Florida
city: Orlando
country: United States
facility: Florida Inst For Clin Res
state: Florida
city: Orlando
country: United States
facility: Florida Institute For Clinical Research
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research, LLC
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute Inc
state: Florida
city: Albany
country: United States
facility: Javara/Privia Med Grp GA,LLC
state: Georgia
city: Honolulu
country: United States
facility: East West Med Res Inst
state: Hawaii
city: Nampa
country: United States
facility: Saltzer Medical Group Research
state: Idaho
city: Skokie
country: United States
facility: Endeavor Health
state: Illinois
city: Slidell
country: United States
facility: Ileana J Tandron APMC
state: Louisiana
city: Hyattsville
country: United States
facility: MedStar Hlth Res Institute
state: Maryland
city: Buckley
country: United States
facility: Northern Pines Hlth Ctr, PC
state: Michigan
city: Las Vegas
country: United States
facility: Palm Research Center Inc-Vegas
state: Nevada
city: Lawrenceville
country: United States
facility: John J Shelmet, MD
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clin Trials, Inc.
state: New Mexico
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Greensboro
country: United States
facility: PharmQuest Life Sciences LLC
state: North Carolina
city: Canton
country: United States
facility: Diab & Endo Assoc of Stark Co
state: Ohio
city: Wadsworth
country: United States
facility: New Venture Medical Research
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ Di Rsrch Ctr
state: Pennsylvania
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Bartlett
country: United States
facility: AM Diabetes And Endocrinology Center
state: Tennessee
city: Chattanooga
country: United States
facility: Chattanooga Medical Research, LLC
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Med Spec LLP
state: Texas
city: Austin
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology
state: Texas
city: Corpus Christi
country: United States
facility: Osvaldo A. Brusco MD PA
state: Texas
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Med Cntr
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Ctr of FW
state: Texas
city: Longview
country: United States
facility: DCOL Ctr for Clin Res
state: Texas
city: Round Rock
country: United States
facility: Texas Diabetes & Endocrinology_Round Rock
state: Texas
city: San Antonio
country: United States
facility: NE Clin Res of San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Sugar Lakes Family Practice PA
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Forest
country: United States
facility: Javara Inc. / Privia Medical Group LLC_Forest
state: Virginia
city: Forest
country: United States
facility: Javara Inc/Privia Md GpLLC Fst
state: Virginia
city: Newport News
country: United States
facility: TPMG Clinical Research
state: Virginia
city: Fortaleza
country: Brazil
facility: Centro de Diabetes Metabolismo e Endocrinologia
state: Ceara
city: Aparecida de Goiania
country: Brazil
facility: Instituto de Ciências Farmacêuticas de Estudos e Pesquisas
state: Goias
city: Curitiba
country: Brazil
facility: Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV
state: Parana
city: Curitiba
country: Brazil
facility: Centro de Diabetes Curitiba
state: Parana
city: São José dos Campos
country: Brazil
facility: Instituto São José dos Campos em Pesquisas Médicas
state: Sao Paulo
city: São Paulo
country: Brazil
facility: BR Trials - Ensaios Clínicos e Consultoria Ltda.
state: Sao Paulo
city: Concord
country: Canada
facility: LMC Clinical Res Thornhill
state: Ontario
city: Courtice
country: Canada
facility: Medical Trust Clinics, Inc.
state: Ontario
city: Hamilton
country: Canada
facility: Wharton Med Clin Trials
state: Ontario
city: London
country: Canada
facility: Western Univ. Cnt for Studies in Fam Med
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clin Res Group,Inc
state: Ontario
city: Toronto
country: Canada
facility: LMC Endo Centres Ltd.(Bayview)
state: Ontario
city: Montreal
country: Canada
facility: Recherche GCP Research
state: Quebec
city: Montreal
country: Canada
facility: Recherche GCP Research
state: Quebec
city: Montreal
country: Canada
facility: LMC Clin Rsrch Inc. (Montreal)
state: Quebec
city: Saint-Laurent
country: Canada
facility: LMC Clin Rsrch Inc. (Montreal)
state: Quebec
city: Quebec
country: Canada
facility: Recherche Clinique Sigma inc
city: Hefei
country: China
facility: Anhui Provincial Hospital-Endocrinology
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital-Endocrinology
state: Beijing
city: ChongQing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Huizhou
country: China
facility: Huizhou Central People's Hospital-Endocrinology
state: Guangdong
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital, Yanghu Branch
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University-Endocrinology
state: Jiangsu
city: Ji'nan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Fudan University-Endocrinology
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Huashan Hospital, Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Fifth People's Hospital-Endocrinology
state: Shanghai
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University-Endocrinology
state: Tianjin
city: Tianjin
country: China
facility: Zhu Xianyi Memorial Hospital of Tianjin Medical University-Endocrinology
state: Tianjin
city: Bois-Guillaume
country: France
facility: Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume
city: Le Coudray
country: France
facility: Les Hopitaux de Chartres-Hopital Louis Pasteur
city: Le Creusot
country: France
facility: Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1
city: Saint Herblain
country: France
facility: Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
city: Venissieux
country: France
facility: Centre de Recherche Clinique Portes Du Sud
city: Athens
country: Greece
facility: Iatriko Psychicou Private Clinic
city: Athens
country: Greece
facility: Evangelismos Hospital
city: Athens
country: Greece
facility: 'G. Gennimatas' General Hospital of Athens
city: Larissa
country: Greece
facility: Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki 'G. Gennimatas
city: Thessaloniki
country: Greece
facility: "Ippokrateio" G.H. of Thessaloniki
city: Thessaloniki
country: Greece
facility: "Thermi" Private Hosital
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G.Papanikolaou"
city: Pécs
country: Hungary
facility: PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum
state: Baranya Vármegye
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Belgyógyászati Klinika
state: Hajdu-Bihar
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: MED-TIMA Kft.
city: Haifa
country: Israel
facility: Linn clinic - Clalit Health Services
city: Herzlia
country: Israel
facility: Clalit sick fund Herzlia
city: Holon
country: Israel
facility: Diabetes Clinic Wolfson MC
city: Jerusalem
country: Israel
facility: Diabetes Unit Hadassah Ein Karem MC
city: Kfar Saba
country: Israel
facility: Diabetes Clinic Meir MC
city: Tel Hashomer
country: Israel
facility: Endrocrinolgy Clinic - Sheba Medical Center
city: Miyazaki-shi
country: Japan
facility: Heiwadai Hospital
state: Miyazaki
city: Chuo-ku, Tokyo
country: Japan
facility: The Institute of Medical Science, Asahi Life Foundation
city: Fukuoka-shi, Fukuoka
country: Japan
facility: Futata Tetsuhiro Clinic Meinohama
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Ibaraki
country: Japan
facility: Naka Kinen Clinic
city: Osaka
country: Japan
facility: Takatsuki Red Cross Hospital
city: Saitama
country: Japan
facility: Shimizu Clinic Fusa
city: Saitama
country: Japan
facility: Soka Sugiura Internal Medicine Clinic_Internal Medicine
city: Sendai-shi, Miyagi
country: Japan
facility: Shinden Higashi Clinic
city: Irkutsk
country: Russian Federation
facility: Irkutsk State Medical Academy of Postgraduate Education
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Endocrinology
city: Novosibirsk
country: Russian Federation
facility: Limited Law Company "Healthy Family" Medicine Center"
city: Omsk
country: Russian Federation
facility: BHI of Omsk Region "City Hospital № 3"
city: Penza
country: Russian Federation
facility: Penza Regional Clinical Hospital named after N.N. Burdenko
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University_Rostov-on-Don
city: Yoshkar-Ola
country: Russian Federation
facility: Polyclinic #2 in Yoshkar-Ola
city: Kosice
country: Slovakia
facility: DIOLI s.r.o.
city: Kosice
country: Slovakia
facility: HUMAN-CARE s.r.o.
city: Kosice
country: Slovakia
facility: Diabetologicka ambulancia DIADAN, s.r.o. Kosice
city: Kosice
country: Slovakia
facility: FNsP L. Pasteura
city: Levice
country: Slovakia
facility: DIA - KONTROL s.r.o.
city: Turcianske Teplice
country: Slovakia
facility: MUDr. Alena Lomencikova, s.r.o
city: Göteborg
country: Sweden
facility: Primary Care Trial Center, PTC ,Gothia Forum
city: Stockholm
country: Sweden
facility: Centrum for Diabetes, Academical Specialist Centrum
city: Örebro
country: Sweden
facility: Enheten för Kliniska Studier (EKS), Örebro
city: Luzern 16
country: Switzerland
facility: Luzerner Kantonsspital
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Zollikerberg
country: Switzerland
facility: Diabetes Adipositas Zentrum Zürich
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan city
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou Branch
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References: