A Research Study Looking at How Well a Combination of the Medicines Semaglutide and NNC0480-0389 Works in People With Type 2 Diabetes

Investigation of the Safety and Efficacy of Semaglutide s.c. in Combination With NNC0480-0389 in Participants With Type 2 Diabetes - a Dose Finding Study

This study is looking at semaglutide in combination with a potential new medicine (NNC0480-0389) in people with type 2 diabetes.

The study is being conducted to see how well semaglutide, in combination with different doses of NNC0480-0389, work to lower blood sugar levels. Results from this study will be used to select the doses of the two medicines for other studies.

Participants will either get:

Semaglutide (a medicine doctors can already prescribe for treatment of type 2 diabetes) in combination with NNC0480-0389 (a potential new medicine) or placebo (a 'dummy' medicine that looks like the medicines but without any medicine).

NNC0480-0389 alone, or semaglutide alone which treatment participant get is decided by chance.

Participant will need to take 2-3 injections once every week during the study. One injection will be with semaglutide or placebo and 1-2 injections will be with NNC0480-0389 or placebo.

Participant must inject the study medicines themself into the stomach, thigh, or upper arm.

The study will last for about 41weeks. Participant will have 20 clinic visits. Participant will have blood samples taken at all clinic visits. At 3 clinic visits, participant will also have an electrocardiogram (ECG). This is a test to check participants heart. Participant will have their eyes checked before or at the start of the study and at the end of the study.

Women can only take part in the study if they are not able to become pregnant

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: NNC0480-0389; Drug: Semaglutide; Drug: Placebo (NNC080-0389); Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Kozloduy, Bulgaria, 3320
    • Medical centre "Zdrave 1" OOD
  • Petrich, Bulgaria, 2850
    • Individual Practice for medical care -Dr Elizabeta Dimitrova
  • Sofia, Bulgaria, 1431
    • UMHAT Aleksandrovska
  • Sofia, Bulgaria, 1632
    • Medical centre - Doverie AD
  • Sofia, Bulgaria, 1797
    • UMHAT Sofiamed
  • Stara Zagora, Bulgaria, 6000
    • "Prevencia-2000-MCOC"
  • Yambol, Bulgaria, 8600
    • Medical center Berbatov
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital Diabetes og Hormonsygdomme
  • Hellerup, Denmark, 2900
    • Center for Klinisk Metabolisk Forskning
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital Endokrinologisk forsknings afsnit 159
• Greece
  • Athens, Greece, GR-11527
    • "Laiko" General Hospital of Athens
  • Athens, Greece, GR-15125
    • Iatriko Athinon (Athens Medical Canter)
  • Athens, Greece, GR-17562
    • Iatriko Athinon 'Palaiou Falirou'
  • Athens, Greece, GR-11528
    • Alexandra General Hospital, Therapeutic Clinic
  • Haidari-Athens, Greece, GR-12462
    • University Hospital of Athens ATTIKON
  • Thessaloniki, Greece, GR-54643
    • EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes
  • Thessaloniki, Greece, GR-57001
    • "Thermi" Private Hosital
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert Egeszsegugyi Szolgaltato Es Kereskedelmi Kft.
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Kórház
  • Budapest, Hungary, 1132
    • MED-TIMA Kft.
  • Budapest, Hungary, 1134
    • MH Egészségügyi Központ
  • Békéscsaba, Hungary, 5600
    • Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház
  • Debrecen, Hungary, 4043
    • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület
  • Gyula, Hungary, 5700
    • Békés Megyei Központi Kórház
  • Kaposvár, Hungary, 7400
    • Kaposi Mór Oktató Kórház
  • Pécs, Hungary, 7623
    • PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum
  • Szombathely, Hungary, H-9700
    • Markusovszky Egyetemi Oktatokorhaz
  • Tatabánya, Hungary, 2800
    • Szent Borbala Korhaz
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4032
      • Debreceni Egyetem Belgyógyászati Klinika
• Japan
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic
  • Kumamoto, Japan, 861-8039
    • Yoshimura clinic
  • Osaka, Japan, 553-0003
    • Kansai Electric Power Hospital
  • Tokyo, Japan, 103-0028
    • Tokyo Center Clinic
  • Tokyo, Japan, 160-0008
    • ToCROM Clinic
  • Tokyo, Japan, 169-0072
    • Higashi-shinjuku clinic
• Poland
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne Sp. z o.o.
  • Lodz, Poland, 90-338
    • Centrum Terapii Wspolczesnej
  • Lodz, Poland, 91-363
    • FutureMeds Sp. z o.o. Lodz
  • Staszow, Poland, 28-200
    • Ko-Med Nova Sp.zo.o. STASZOW
  • Torun, Poland, 87-100
    • Osrodek Badan Klinicznych Clinsante
  • Warszawa, Poland, 02-507
    • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
  • Warszawa, Poland, 00-215
    • Centrum Medyczne AMED Warszawa
  • Wroclaw, Poland, 50-088
    • FutureMeds Sp. z o.o.
  • Zabrze, Poland, 41-800
    • SPSK nr 1 im. prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach, ul. 3-go Maja 13/15 41-800 Zabrze
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-879
      • NZOZ Vita-Diabetica Malgorzata Buraczyk
• Russian Federation
  • Novosibirsk, Russian Federation, 630005
    • LLC RC Medical
  • Penza, Russian Federation, 440026
    • Penza Regional Clinical Hospital named after N.N. Burdenko
  • Saint-Petersburg, Russian Federation, 194356
    • Medinet LLC
  • Russia
    • Tumen, Russia, Russian Federation, 625023
      • Tumen State Medical University
• Serbia
  • Belgrade, Serbia, 11000
    • Endocrinology, Diabetes and Metabolism Diseases Clinic
  • Belgrade, Serbia, 11000
    • CHC Zvezdara, Clinical department for endocrinology
  • Kragujevac, Serbia, 34000
    • Clinical Centre Kragujevac, Internal Diseases Clinic, Endocr
• United States
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Clin Res-Chula Vista
    • Escondido, California, United States, 92025
      • Headlands Research California, LLC
    • Fullerton, California, United States, 92835
      • St. Jos Heritage Hlthcr_Fllrtn
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research San Diego
    • Lancaster, California, United States, 93534
      • First Valley Med Grp Lancaster
    • Lomita, California, United States, 90717
      • Torrance Clin Res Inst, Inc.
    • Los Angeles, California, United States, 90057
      • Velocity Clin Res Wstlke
    • Northridge, California, United States, 91325
      • Valley Clinical Trials, Inc.
    • Riverside, California, United States, 92503
      • Artemis Insitute for Clin Res
    • San Diego, California, United States, 92103
      • Artemis Institute for Clin Res
    • West Hills, California, United States, 91304
      • San Fernando Valley Hlth Inst
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Northeast Research Institute
    • Miami, Florida, United States, 33175
      • Reyes Clinical Research, Inc
    • Miramar, Florida, United States, 33027
      • South Broward Research LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34243
      • Headlands Research - Sarasota
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes & Endo Res Ctr
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-5804
      • Brigham & Women's Hospital
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare, PLC
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Str Med Grp, PLLC
  • New York
    • Albany, New York, United States, 12203
      • Albany Medical College - Endo
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest Life Sciences LLC
    • Greenville, North Carolina, United States, 27834
      • Physicians East Endocrinology
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare/Research
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Advanced Med Res Maumee
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
      • Essential Medical Research LLC
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Dallas, Texas, United States, 75390-9302
      • UT Southwestern Med Cntr
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc
    • San Antonio, Texas, United States, 78230
      • VIP Trials_San Antonio
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening
• Participants treated with diet and exercise as monotherapy or in combination with stable daily dose(s) greater than or equal to 90 days before screening of any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose
• HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive)
• BMI greater than or equal to 25 and below 40 kg/m^2

Exclusion Criteria:

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days and prior insulin treatment for gestational diabetes are allowed
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 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
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic cardiovascular, gastrointestinal, or endocrinological conditions (except conditions associated with T2D)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2.4 mg semaglutide + 2.4 mg NNC0480-0389; subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide.	Drug: NNC0480-0389; A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.; Drug: Semaglutide; A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.
Placebo Comparator: Placebo (semaglutide) + placebo ( 2.4 mg NNC0480-0389); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide).	Drug: Placebo (NNC080-0389); A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.; Drug: Placebo (semaglutide); A weekly dose of placebo (semaglutide). The study will last for about 41weeks.
Experimental: 2.4 mg semaglutide + 7.2 mg NNC0480-0389; subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide	Drug: NNC0480-0389; A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.; Drug: Semaglutide; A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.
Experimental: 2.4 mg semaglutide + 12.0 mg NNC0480-0389; subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide	Drug: NNC0480-0389; A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.; Drug: Semaglutide; A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.
Experimental: 2.4 mg semaglutide + 21.6 mg NNC0480-0389; subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide	Drug: NNC0480-0389; A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.; Drug: Semaglutide; A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.
Experimental: NNC0480-0389 + placebo (semaglutide); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. placebo (semaglutide)	Drug: NNC0480-0389; A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.; Drug: Placebo (semaglutide); A weekly dose of placebo (semaglutide). The study will last for about 41weeks.
Placebo Comparator: Placebo (semaglutide) + placebo ( 7.2 mg NNC0480-0389); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide).	Drug: Placebo (NNC080-0389); A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.; Drug: Placebo (semaglutide); A weekly dose of placebo (semaglutide). The study will last for about 41weeks.
Placebo Comparator: Placebo (semaglutide) + placebo ( 12.0 mg NNC0480-0389); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide).	Drug: Placebo (NNC080-0389); A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.; Drug: Placebo (semaglutide); A weekly dose of placebo (semaglutide). The study will last for about 41weeks.
Placebo Comparator: Placebo (semaglutide) + placebo ( 21.6 mg NNC0480-0389); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide).	Drug: Placebo (NNC080-0389); A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.; Drug: Placebo (semaglutide); A weekly dose of placebo (semaglutide). The study will last for about 41weeks.
Experimental: Semaglutide 2.4 mg + placebo (NNC0480-0389); subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. semaglutide.	Drug: Semaglutide; A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.; Drug: Placebo (NNC080-0389); A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	percentage-point	From baseline (week 0) to visit 24 (week 34)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting plasma glucose (FPG)	measured in mmol/L	From baseline (week 0) to visit 24 (week 34)
Change in body weight (kg)	measured in kg	From baseline (week 0) to visit 24 (week 34)
Change in body weight (%)	measured in percent	From baseline (week 0) to visit 24 (week 34)
Change in waist circumference	measured in cm	From baseline (week 0) to visit 24 (week 34)
Change in systolic blood pressure (SBP)	measured in mmHg	From baseline (week 0) to visit 24 (week 34)
Relative change in total cholesterol	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in high-density lipoprotein (HDL) cholesterol	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in low-density lipoprotein (LDL) cholesterol	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in very-low-density lipoprotein (VLDL) cholesterol	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in triglycerides	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in free fatty acids	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in Apolipoprotein B (ApoB)	ratio	From baseline (week 0) to visit 24 (week 34)
Relative change in high sensitivity C-Reactive Protein (hsCRP)	ratio	From baseline (week 0) to visit 24 (week 34)
Number of treatment-emergent adverse events (TEAEs)	Count of events	From baseline (week 0) to visit 25 (week 39)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): February 13, 2023
• Study Completion (Actual): March 23, 2023

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN9389-4606; U1111-1259-2741 (Other Identifier: World Health Organization (WHO)); 2020-004863-14 (EudraCT Number); jRCT2031210474 (Other Identifier: Japanese Registration 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