A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Diet and Exercise (REIMAGINE 1)

Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) s.c. in Doses 2.4 mg/2.4 mg and 1.0 mg/1.0 mg Once Weekly Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Diet and Exercise

This study will look at how much CagriSema helps participants with type 2 diabetes lower their blood sugar and body weight. CagriSema is a new investigational medicine. Doctors may not yet prescribe CagriSema. CagriSema will be compared to a "dummy" medicine (also called "placebo") that has no effect on the body. Participants will get either CagriSema or "dummy" medicine. Which treatment participants get is decided by chance. For each participant, the study will last for about one year.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Cagrilintide; Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Not yet recruiting
      • Chinese People's Liberation Army General Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanjing Medical University_Nanjing
    • Zhenjiang, Jiangsu, China, 212001
      • Not yet recruiting
      • The Affiliated Hospital of Jiangsu University_Zhenjiang
  • Shandong
    • Ji'Nan, Shandong, China, 250000
      • Not yet recruiting
      • Jinan Central Hospital
• Hungary
  • Hajdu-Bihar Varmegye
    • Debrecen, Hajdu-Bihar Varmegye, Hungary, 4025
      • Not yet recruiting
      • Belinus Bt.
  • Szabolcs-Szatmar Varmegye
    • Nyíregyháza, Szabolcs-Szatmar Varmegye, Hungary, 4405
      • Not yet recruiting
      • Borbánya Praxis E.Ü. Kft.
• Italy
  • Bergamo, Italy, 24127
    • Not yet recruiting
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Catanzaro, Italy, 88100
    • Not yet recruiting
    • Policlinico Mater Domini Università di Catanzaro
  • Milano, Italy, 20132
    • Not yet recruiting
    • IRCCS Ospedale San Raffaele Milano
  • Roma, Italy, 00161
    • Not yet recruiting
    • Azienda Ospealiero Universitaria Policlinico Umberto I
• Poland
  • Białystok, Poland, 15-794
    • Not yet recruiting
    • Renew Clinic Bialystok
  • Lodz, Poland, 90-338
    • Not yet recruiting
    • Centrum Terapii Wspolczesnej
  • Warszawa, Poland, 00-710
    • Not yet recruiting
    • NBR Polska Tomasz Klodawski
  • Podkarpackie
    • Rzeszow, Podkarpackie, Poland, 35-055
      • Not yet recruiting
      • Centrum Medyczne Medyk Sp. z o.o.
• Saudi Arabia
  • Al Ahsa, Saudi Arabia, 36428
    • Not yet recruiting
    • King Abdulaziz Hospital-Al Ahsa-National Guard
  • Jeddah, Saudi Arabia, 21423
    • Not yet recruiting
    • National Guard Hospital - Jeddah
  • Riyadh, Saudi Arabia, 11525
    • Not yet recruiting
    • King Fahad Medical City
  • Riyadh, Saudi Arabia, 12372
    • Not yet recruiting
    • King Khaled University Hospital,King Saud Univ. Med. City
  • Riyadh, Saudi Arabia, 12769
    • Not yet recruiting
    • King Salman Bin Abdulaziz Hospital
• Serbia
  • Belgrade, Serbia, 11080
    • Not yet recruiting
    • Clinical hospital center Bezanijska Kosa
  • Belgrade, Serbia, 11000
    • Not yet recruiting
    • CHC Zvezdara, Clinical department for endocrinology
  • Belgrade, Serbia, 11080
    • Not yet recruiting
    • Clinical Hospital Centre Zemun
• United States
  • California
    • Huntington Park, California, United States, 90255
      • Recruiting
      • National Research Institute_Huntington Park
    • Northridge, California, United States, 91325
      • Recruiting
      • Valley Clinical Trials, Inc.
    • Santa Ana, California, United States, 92701
      • Recruiting
      • Southern California Dermatology
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Encore Medical Research LLC
  • Kansas
    • Newton, Kansas, United States, 67114
      • Not yet recruiting
      • Alliance for Multispec Res
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Brigham & Women'S Hospital
  • Michigan
    • Troy, Michigan, United States, 48098
      • Recruiting
      • Arcturus Healthcare, PLC
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Recruiting
      • Holston Medical Group
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Velocity Clinical Res-Dallas
    • San Antonio, Texas, United States, 78233
      • Recruiting
      • Northeast Clinical Research of San Antonio
    • Shavano Park, Texas, United States, 78231
      • Recruiting
      • Consano Clinical Research, LLC
    • Shavano Park, Texas, United States, 78231
      • Not yet recruiting
      • Consano Clinical Research, LLC
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Recruiting
      • TPMG Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female
• Age 18 years or above at the time of signing the informed consent
• Diagnosed with type 2 diabetes >=30 days before screening
• HbA1c 7.0-9.5 percent (53-80 millimoles per mole [mmol/mol]) (both inclusive) as determined by central laboratory at screening
• Body mass index (BMI) >=23 kilograms per square meter (kg/m^2) at screening. BMI will be calculated in the electronic case report form (eCRF) based on height and body weight at screening

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
• Renal impairment with estimated Glomerular Filtration Rate less than 30 milliliter per minute per 1.73 square meter (ml/min/1.73 m^2) as determined by central laboratory at screening
• Treatment with any medication for the indication of diabetes or obesity within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed
• History of use of any injectable therapy for diabetes or obesity. However, short term insulin treatment for a maximum of 14 consecutive 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CagriSema Dose 2; Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 16-week dose escalation period until target dose (dose 2) of CagriSema (cagrilintide and semaglutide) is achieved and maintained up to 24 weeks.	Drug: Cagrilintide; Participants will receive once-weekly cagrilintide subcutaneously.; Drug: Semaglutide; Participants will receive once-weekly semaglutide subcutaneously.
Placebo Comparator: Placebo Dose 2; Participants will receive once-weekly s.c injection of placebo matched to Cagrisema (cagrilintide and semaglutide) dose 2 for 40 weeks.	Drug: Placebo; Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously.
Active Comparator: Cagrisema Dose 1; Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 8-week dose escalation period until target dose (dose 1) of CagriSema (cagrilintide and semaglutide) is achieved and maintained up to 32 weeks.	Drug: Cagrilintide; Participants will receive once-weekly cagrilintide subcutaneously.; Drug: Semaglutide; Participants will receive once-weekly semaglutide subcutaneously.
Placebo Comparator: Placebo Dose 1; Participants will receive once-weekly s.c injection of placebo matched to Cagrisema (cagrilintide and semaglutide) dose 1 for 40 weeks.	Drug: Placebo; Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycated haemoglobin (HbA1c)	Measured as percentage (%)-points.	From baseline (week 0) to end of treatment (week 40)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in body weight	Measured in %.	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve greater than or equal to (>=) 10% body weight reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve >=15% body weight reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol])	Measured as count of participants.	At end of treatment (week 40)
Number of participants who achieve HbA1c target values of less than or equal to (<=) 6.5% (<= 48 mmol/mol)	Measured as count of participants.	At end of treatment (week 40)
Change in Fasting Plasma Glucose (FPG)	Measured in millimoles per liter (mmol/L).	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve >=5% body weight reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve >=20% body weight reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Change in waist circumference	Measured in centimeters (cm).	From baseline (week 0) to end of treatment (week 40)
Change in systolic blood pressure (SBP)	Measured in millimeters of mercury (mmHg).	From baseline (week 0) to end of treatment (week 40)
Change in diastolic blood pressure (DBP)	Measured in mmHg.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in high sensitivity C-reactive protein (hsCRP)	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Total cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: High-density lipoprotein (HDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Low-density lipoprotein (LDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Very low-density lipoprotein (VLDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Triglycerides	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Free fatty acids	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to baseline in lipids: Non-HDL cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Number of participants who achieve type 2 diabetes (T2D) remission (HbA1c <6.5% and no antidiabetic medication)	Measured as count of participants.	At end of study (week 52)
Ratio to baseline in oral glucose tolerance test (OGTT) based oral glucose disposition index (DIo)	Measured as ratio.	From baseline (week 0) to end of treatment (week 40)
Change in experienced level of energy as measured by the SF-36v2 Health Survey Acute (SF-36v2) Vitality score	Measured as score points. SF-36v2 Acute measures Health-Related Quality of Life (HRQoL). The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The vitality score range is from 25.6 to 69.1.	From baseline (week 0) to end of treatment (week 40)
Change in SF-36v2 score: Physical Component Summary score	Measured as score points. SF-36v2 Acute measures HRQoL. The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The score range for physical component summary is 6.1 to 79.7.	From baseline (week 0) to end of treatment (week 40)
Change in SF-36v2 score: Mental Component Summary score	Measured as score points. SF-36v2 Acute measures HRQoL. The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The score range for mental component summary score is -3.8 to 78.7.	From baseline (week 0) to end of treatment (week 40)
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score	Measured as score points. DTSQs measures treatment satisfaction and diabetes-specific quality of life. The measure consists of 8 items yielding 1 global score and 2 single item scores. Higher scores on the global score indicate greater satisfaction with treatment. Lower scores on the single-item scores indicate BG levels closer to the ideal, while higher scores indicate problems. Single-item scores (score range): Perceived frequency of hyperglycaemia (0-6), Perceived frequency of hypoglycaemia (0-6). Global score (score range): Total Treatment Satisfaction (0-36).	From baseline (week 0) to end of treatment (week 40)
Change in leptin	Measured in nanograms per milliliter (ng/mL).	From baseline (week 0) to end of treatment (week 40)
Change in soluble leptin receptor	Measured in ng/mL.	From baseline (week 0) to end of treatment (week 40)
Number of Treatment Emergent Adverse Events (TEAEs)	Measured as count of events.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol (54 milligrams per deciliter [mg/dL]), confirmed by blood glucose (BG) meter	Measured as count of episodes.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold	Measured as count of episodes.	From baseline (week 0) to end of treatment + 7 weeks (week 47)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2024
• Primary Completion (Estimated): August 12, 2025
• Study Completion (Estimated): November 4, 2025

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 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; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: NN9388-4895; 2022-502677-42 (Other Identifier: European Medical Agency (EMA)); U1111-1283-0404 (Other Identifier: World Health Organization (WHO))

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