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) (COMBINE 2)

February 20, 2024 updated by: Novo Nordisk A/S

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

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.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

683

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Ceara
      • Fortaleza, Ceara, Brazil, 60150-162
        • Centro De Diabetes Metabolismo E Endocrinologia
    • Goias
      • Aparecida de Goiania, Goias, Brazil, 74935-530
        • Instituto de Ciências Farmacêuticas de Estudos e Pesquisas
    • Parana
      • Curitiba, Parana, Brazil, 80810-040
        • Centro de Diabetes Curitiba
      • Curitiba, Parana, Brazil, 80045-170
        • Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV
    • Sao Paulo
      • São José dos Campos, Sao Paulo, Brazil, 12243-280
        • Instituto São José dos Campos em Pesquisas Médicas
      • São Paulo, Sao Paulo, Brazil, 05003-090
        • BR Trials - Ensaios Clínicos e Consultoria Ltda.
      • Quebec, Canada, G1G 3Y8
        • Recherche Clinique Sigma inc
    • Ontario
      • Concord, Ontario, Canada, L4K 4M2
        • LMC (Thornhill)
      • Hamilton, Ontario, Canada, L8L 5G8
        • Wharton Med Clin Trials
      • London, Ontario, Canada, N6G 2M1
        • Western Univ. Cnt for Studies in Fam Med
      • Oshawa, Ontario, Canada, L1G4T3
        • Medical Trust Clinics, Inc.
      • Sarnia, Ontario, Canada, N7T 4X3
        • Bluewater Clin Res Group,Inc
      • Toronto, Ontario, Canada, M4G 3E8
        • LMC Endo Centres Ltd.(Bayview)
    • Quebec
      • Montreal, Quebec, Canada, H1M 1B1
        • Recherche GCP Research
      • Montreal, Quebec, Canada, H4T 1Z9
        • LMC Clin Rsrch Inc. (Montreal)
      • Saint-Laurent, Quebec, Canada, H4T 1Z9
        • LMC Clin Rsrch Inc. (Montreal)
    • Anhui
      • Hefei, Anhui, China, 230001
        • Anhui provincial hospital
    • Beijing
      • Beijing, Beijing, China, 100044
        • Peking University People's Hospital
    • Chongqing
      • ChongQing, Chongqing, China, 404000
        • Chongqing University Three Gorges Hospital
    • Guangdong
      • Huizhou, Guangdong, China, 516001
        • Huizhou Central People's Hospital
    • Jiangsu
      • Changzhou, Jiangsu, China, 213003
        • Changzhou No.2 People's Hospital, Yanghu Branch
      • Nanjing, Jiangsu, China, 210011
        • The Second Affiliated Hospital of Nanjing Medical University_Nanjing
    • Shandong
      • Jin'an, Shandong, China, 250013
        • Jinan Central Hospital
    • Shanghai
      • Shanghai, Shanghai, China, 200240
        • Shanghai Fifth People's Hospital
      • Shanghai, Shanghai, China, 200040
        • Shanghai Huashan Hospital, Affiliated to Fudan University
    • Tianjin
      • Tianjin, Tianjin, China, 300052
        • General Hospital of Tianjin Medical University
      • Tianjin, Tianjin, China, 300070
        • Zhu Xianyi Memorial Hospital of Tianjin Medical University
      • Bois-Guillaume, France, 76230
        • Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume
      • Le Coudray, France, 28630
        • Les Hopitaux de Chartres-Hopital Louis Pasteur
      • Le Creusot, France, 71200
        • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1
      • Saint Herblain, France, 44800
        • Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1
      • Toulouse, France, 31054
        • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
      • Venissieux, France, 69200
        • Groupe Hospitalier Mutualiste Des Portes Du Sud
      • Athens, Greece, 115 25
        • Iatriko Psychicou Private Clinic
      • Athens, Greece, GR-10676
        • Evangelismos Hospital
      • Athens, Greece, GR-115 27
        • 'G. Gennimatas' General Hospital of Athens
      • Larissa, Greece, GR-41110
        • Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease
      • Thessaloniki, Greece, GR-54635
        • General Hospital of Thessaloniki 'G. Gennimatas
      • Thessaloniki, Greece, GR-57001
        • "Thermi" Private Hosital
      • Thessaloniki, Greece, GR-57010
        • General Hospital of Thessaloniki "G.Papanikolaou"
      • Thessaloniki, Greece, GR-54642
        • "Ippokrateio" G.H. of Thessaloniki
      • Budapest, Hungary, 1132
        • MED-TIMA Kft.
    • Baranya Vármegye
      • Pécs, Baranya Vármegye, Hungary, 7623
        • PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum
    • Hajdu-Bihar
      • Debrecen, Hajdu-Bihar, Hungary, 4032
        • Debreceni Egyetem Belgyógyászati Klinika
      • Debrecen, Hajdu-Bihar, Hungary, H-4043
        • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület
      • Haifa, Israel, 35152
        • Linn clinic - Clalit Health Services
      • Herzlia, Israel, 4630945
        • Clalit sick fund Herzlia
      • Holon, Israel, 58100
        • Diabetes Clinic Wolfson MC
      • Jerusalem, Israel, 91120
        • Diabetes Unit Hadassah Ein Karem MC
      • Kfar Saba, Israel, 44281
        • Diabetes Clinic Meir MC
      • Tel Hashomer, Israel, 52621
        • Endrocrinolgy Clinic - Sheba Medical Center
      • Chuo-ku, Tokyo, Japan, 103-0002
        • The Institute of Medical Science, Asahi Life Foundation
      • Fukuoka-shi, Fukuoka, Japan, 819-0006
        • Futata Tetsuhiro Clinic Meinohama
      • Gifu, Japan, 501-1194
        • Gifu University Hospital
      • Ibaraki, Japan, 311-0113
        • Naka Kinen Clinic
      • Osaka, Japan, 569-1045
        • Takatsuki Red Cross Hospital
      • Saitama, Japan, 336-0967
        • Shimizu Clinic Fusa
      • Saitama, Japan, 340-0015
        • Soka Sugiura Internal Medicine Clinic_Internal Medicine
      • Sendai-shi, Miyagi, Japan, 983-0039
        • Shinden Higashi Clinic
    • Miyazaki
      • Miyazaki-shi, Miyazaki, Japan, 880-0034
        • Heiwadai Hospital
      • Irkutsk, Russian Federation, 664049
        • Irkutsk State Medical Academy of Postgraduate Education
      • Moscow, Russian Federation, 117292
        • National Medical Research Center of Endocrinology
      • Novosibirsk, Russian Federation, 630099
        • Limited Law Company "Healthy Family" Medicine Center"
      • Omsk, Russian Federation, 644029
        • BHI of Omsk Region "City Hospital № 3"
      • Penza, Russian Federation, 440052
        • Penza Regional Clinical Hospital named after N.N. Burdenko
      • Rostov-on-Don, Russian Federation, 344022
        • Rostov State Medical University_Rostov-on-Don
      • Yoshkar-Ola, Russian Federation, 424004
        • Polyclinic #2 in Yoshkar-Ola
      • Kosice, Slovakia, 040 01
        • Human-Care s.r.o.
      • Kosice, Slovakia, 040 01
        • DIOLI s.r.o.
      • Kosice, Slovakia, 04011
        • Diabetologicka ambulancia DIADAN, s.r.o. Kosice
      • Kosice, Slovakia, 04190
        • FNsP L. Pasteura
      • Levice, Slovakia, 93401
        • DIA - KONTROL s.r.o.
      • Turcianske Teplice, Slovakia, 039 01
        • MUDr. Alena Lomencikova, s.r.o
      • Göteborg, Sweden, 413 46
        • Primary Care Trial Center, PTC ,Gothia Forum
      • Stockholm, Sweden, 113 65
        • Centrum for Diabetes, Academical Specialist Centrum
      • Örebro, Sweden, 703 62
        • Enheten för Kliniska Studier (EKS), Örebro
      • Luzern 16, Switzerland, 6000
        • Luzerner Kantonsspital
      • Olten, Switzerland, 4600
        • Kantonsspital Olten
      • Zollikerberg, Switzerland, 8125
        • Diabetes Adipositas Zentrum Zürich
      • Taichung City, Taiwan, 402
        • Chung Shan Medical University Hospital
      • Tainan City, Taiwan, 704
        • National Cheng Kung University Hospital
      • Tainan City, Taiwan, 710
        • Chi Mei Medical Center
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taoyuan city, Taiwan, 333
        • Chang Gung Medical Foundation - Linkou Branch
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of AL at Birmingham_BRM
    • Arizona
      • Gilbert, Arizona, United States, 85296
        • Pri Med Grp dba/Gil Ctr Fam
      • Sun City West, Arizona, United States, 85375
        • Clinical Research Institute of Arizona
    • California
      • Concord, California, United States, 94520
        • John Muir Physician Network
      • Los Angeles, California, United States, 90057
        • Velocity Clin Res Wstlke
      • Northridge, California, United States, 91325
        • Valley Clinical Trials, Inc.
      • Toluca Lake, California, United States, 91602
        • Premier Medical Center, Inc.
    • Florida
      • Fleming Island, Florida, United States, 32003
        • Northeast Research Institute
      • Jacksonville, Florida, United States, 32216
        • Est Cst Inst for Rsrch,Jksnvil
      • Jacksonville, Florida, United States, 32204
        • Northeast Res Inst. Inc.
      • Miramar, Florida, United States, 33027
        • South Broward Research LLC
      • Mount Dora, Florida, United States, 32757
        • Adult Medicine of Lake County, Inc.
      • Orlando, Florida, United States, 32825
        • Florida Institute For Clinical Research
      • Orlando, Florida, United States, 32825
        • Florida Inst For Clin Res
      • Oviedo, Florida, United States, 32765
        • Oviedo Medical Research, LLC
      • West Palm Beach, Florida, United States, 33401
        • Metabolic Research Institute Inc
    • Georgia
      • Albany, Georgia, United States, 31707
        • Javara/Privia Med Grp GA,LLC
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • East West Med Res Inst
    • Idaho
      • Nampa, Idaho, United States, 83686-6011
        • Saltzer Medical Group Research
    • Illinois
      • Skokie, Illinois, United States, 60077
        • NorthShore Univ Hlth Sys
    • Louisiana
      • Slidell, Louisiana, United States, 70461-4231
        • Ileana J Tandron APMC
    • Maryland
      • Hyattsville, Maryland, United States, 20782
        • MedStar Hlth Res Institute
    • Michigan
      • Buckley, Michigan, United States, 49620
        • Northern Pines Hlth Ctr, PC
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Palm Research Center Inc-Vegas
    • New Jersey
      • Lawrenceville, New Jersey, United States, 08648
        • John J Shelmet, MD
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Albuquerque Clin Trials, Inc.
    • New York
      • West Seneca, New York, United States, 14224
        • Southgate Medical Group, LLP
    • North Carolina
      • Greensboro, North Carolina, United States, 27408
        • PharmQuest Life Sciences LLC
    • Ohio
      • Canton, Ohio, United States, 44718
        • Diab & Endo Assoc of Stark Co
      • Wadsworth, Ohio, United States, 44281
        • New Venture Medical Research
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson Univ Di Rsrch Ctr
    • South Carolina
      • Summerville, South Carolina, United States, 29485
        • Palmetto Clinical Research
    • Tennessee
      • Bartlett, Tennessee, United States, 38133
        • AM Diabetes And Endocrinology Center
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Medical Research, LLC
    • Texas
      • Amarillo, Texas, United States, 79106
        • Amarillo Med Spec LLP
      • Austin, Texas, United States, 78749
        • Texas Diabetes & Endocrinology
      • Austin, Texas, United States, 78731
        • Texas Diab & Endo, P.A.
      • Corpus Christi, Texas, United States, 78414
        • Osvaldo A. Brusco MD PA
      • Dallas, Texas, United States, 75231
        • North Texas Endocrine Center
      • Dallas, Texas, United States, 75390-9302
        • UT Southwestern Med Cntr
      • Fort Worth, Texas, United States, 76132
        • Diabetes and Thyroid Ctr of FW
      • Longview, Texas, United States, 75605
        • DCOL Ctr for Clin Res
      • Round Rock, Texas, United States, 78681
        • Texas Diabetes & Endocrinology_Round Rock
      • San Antonio, Texas, United States, 78233
        • NE Clin Res of San Antonio
      • Sugar Land, Texas, United States, 77479
        • Sugar Lakes Family Practice PA
    • Utah
      • Saint George, Utah, United States, 84790
        • Chrysalis Clinical Research
    • Virginia
      • Forest, Virginia, United States, 24551
        • Javara Inc/Privia Md GpLLC Fst
      • Forest, Virginia, United States, 24551
        • Javara Inc. / Privia Medical Group LLC_Forest
      • Newport News, Virginia, United States, 23606
        • TPMG Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IcoSema
Participants will get once weekly dose

IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen.

For about 1 year and 1 month.

Experimental: Semaglutide
Participants will get once weekly dose
Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in glycated haemoglobin (HbA1c)
Time Frame: From baseline week 0 (V2) to week 52 (V54)
Percentage-point
From baseline week 0 (V2) to week 52 (V54)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
Time Frame: From baseline week 0 (V2) to week 57 (V56)
Number of episodes
From baseline week 0 (V2) to week 57 (V56)
Change in fasting plasma glucose (FPG)
Time Frame: From baseline week 0 (V2) to week 52 (V54)
Measured in mmol/L
From baseline week 0 (V2) to week 52 (V54)
Change in body weight
Time Frame: From baseline week 0 (V2) to week 52 (V54)
Measured in Kg
From baseline week 0 (V2) to week 52 (V54)
Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter)
Time Frame: From baseline week 0 (V2) to week 57 (V56)
Number of episodes
From baseline week 0 (V2) to week 57 (V56)
Number of severe hypoglycaemic episodes (level 3)
Time Frame: From baseline week 0 (V2) to week 57 (V56)
Number of episodes
From baseline week 0 (V2) to week 57 (V56)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2022

Primary Completion (Actual)

December 13, 2023

Study Completion (Actual)

January 16, 2024

Study Registration Dates

First Submitted

February 10, 2022

First Submitted That Met QC Criteria

February 17, 2022

First Posted (Actual)

February 28, 2022

Study Record Updates

Last Update Posted (Estimated)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • NN1535-4592
  • U1111 1260 8268 (Other Identifier: World Health Organization (WHO))
  • 2020 005308 21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

"According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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