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A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor (REIMAGINE 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06065540
Recruitment Status : Recruiting
First Posted : October 4, 2023
Last Update Posted : May 14, 2024
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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Brief Summary:
The study will look at how well CagriSema helps people lower their blood sugar and body weight. CagriSema is a new weekly medicine that combines two medicines called semaglutide and cagrilintide. CagriSema will be compared to the two medicines semaglutide and cagrilintide, when they are taken alone. CagriSema will also be compared to a "dummy" medicine without any active ingredient. The study will be done in participants who have type 2 diabetes. Participants will take the study medicine together with the current diabetes medicine (metformin with or without an SGLT2 inhibitor).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Cagrilintide Drug: Semaglutide Drug: Placebo cagrilintide Drug: Placebo semaglutide Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) s.c. in Doses 2.4/2.4 mg and 1.0/1.0 mg Once Weekly Versus Semaglutide 2.4 mg and 1.0 mg, Cagrilintide 2.4 mg and Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Metformin With or Without an SGLT2 Inhibitor
Actual Study Start Date : September 27, 2023
Estimated Primary Completion Date : November 26, 2025
Estimated Study Completion Date : January 14, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight
Drug Information available for: Semaglutide

Arms and Interventions
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Arm Intervention/treatment
Experimental: CagriSema 2.4 mg/2.4 mg
Participants will receive once-weekly subcutaneous (s.c) injections of 2.4 mg cagrilintide and 2.4 mg semaglutide for 68 weeks.
 Drug: Cagrilintide
Participants will receive once-weekly s.c injection of cagrilintide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of cagrilintide is reached.

Drug: Semaglutide
Participants will receive once-weekly s.c injection of semaglutide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of semaglutide is reached.
Experimental: CagriSema 1.0 mg/1.0 mg
Participants will receive once-weekly s.c injections of 1.0 mg cagrilintide and 1.0 mg semaglutide for 68 weeks.
 Drug: Cagrilintide
Participants will receive once-weekly s.c injection of cagrilintide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of cagrilintide is reached.

Drug: Semaglutide
Participants will receive once-weekly s.c injection of semaglutide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of semaglutide is reached.
Active Comparator: Semaglutide 2.4 mg
Participants will receive once-weekly s.c injection of 2.4 mg semaglutide for 68 weeks.
 Drug: Semaglutide
Participants will receive once-weekly s.c injection of semaglutide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of semaglutide is reached.
Active Comparator: Semaglutide 1.0 mg
Participants will receive once-weekly s.c injection of 1.0 mg semaglutide for 68 weeks.
 Drug: Semaglutide
Participants will receive once-weekly s.c injection of semaglutide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of semaglutide is reached.
Active Comparator: Cagrilintide 2.4 mg
Participants will receive once-weekly s.c injection of 2.4 mg cagrilintide for 68 weeks.
 Drug: Cagrilintide
Participants will receive once-weekly s.c injection of cagrilintide at escalating doses every week until maintenance dose of 2.4 mg and 1.0 mg of cagrilintide is reached.
Placebo Comparator: Placebo 2.4 mg/2.4 mg
Participants will receive once-weekly s.c injection of placebo matched to 2.4 mg cagrilintide and 2.4 mg semaglutide for 68 weeks.
 Drug: Placebo cagrilintide
Participants will receive placebo matched to cagrilintide subcutaneously.

Drug: Placebo semaglutide
Participants will receive placebo matched to semaglutide subcutaneously.
Placebo Comparator: Placebo 1.0 mg/1.0 mg
Participants will receive once-weekly s.c injection of placebo matched to 1.0 mg cagrilintide and 1.0 mg semaglutide for 68 weeks.
 Drug: Placebo cagrilintide
Participants will receive placebo matched to cagrilintide subcutaneously.

Drug: Placebo semaglutide
Participants will receive placebo matched to semaglutide subcutaneously.


Outcome Measures
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Primary Outcome Measures :
  1. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg versus 1.0 mg): Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  2. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg versus 1.0 mg): Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage.


Secondary Outcome Measures :
  1. CagriSema 2.4 mg/2.4 mg versus cagrilintide 2.4 mg: Change in HbA1c [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  2. CagriSema 2.4 mg/2.4 mg versus cagrilintide 2.4 mg: Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage.

  3. CagriSema 2.4 mg/2.4 mg versus semaglutide 1.0 mg: Change in HbA1c [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  4. CagriSema 2.4 mg/2.4 mg versus semaglutide 1.0 mg: Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage.

  5. Cagrilintide 2.4 mg versus placebo: Change in HbA1c [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  6. Cagrilintide 2.4 mg versus placebo: Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage.

  7. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Achievement of greater than or equal to (>=) 10 percent (%) weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as count of participants.

  8. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Achievement of >= 15 % weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as count of participants.

  9. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Achievement of >= 20 % weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as count of participants.

  10. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): CGM - Change in time in Tight Target Range (TITR) 3.9-7.8 millimoles per litre (mmol/L) (70-140 milligrams per decilitre [mg/dL]) [ Time Frame: From baseline (week -3) to end of treatment (week 68) ]
    Measured in percentage-points.

  11. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Systolic Blood Pressure (SBP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in millimeters of mercury (mmHg).

  12. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in triglycerides [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of triglycerides.

  13. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in non-High Density Lipoprotein (HDL) cholesterols [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of non-HDL cholesterol.

  14. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): CGM - Change in Time In Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) [ Time Frame: From baseline (week -3) to end of treatment (week 68) ]
    Measured in percentage-points.

  15. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in high sensitivity C-Reactive Protein (hsCRP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of hsCRP.

  16. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Fasting Plasma Glucose (FPG) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in mmol/L.

  17. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Achievement of HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol]) [ Time Frame: At end of treatment (week 68) ]
    Measured as count of participants.

  18. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Achievement of HbA1c target values of less than or equal to (≤)6.5% (≤48 mmol/mol) [ Time Frame: At end of treatment (week 68) ]
    Measured as count of participants.

  19. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): CGM - Change in time above range, >10.0 mmol/L (>180 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  20. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): CGM - Change in time above range, >13.9 mmol/L (>250 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in percentage-points.

  21. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): CGM - Within-day glycaemic variability (% coefficient of variation [CV]) [ Time Frame: At end of treatment (week 68) ]
    Measured in percentage.

  22. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg versus 1.0 mg): Achievement of ≥ 5 % weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as count of participants.

  23. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in centimetre.

  24. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Diastolic Blood Pressure (DBP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured in mmHg.

  25. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in total cholesterol [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of total cholesterol.

  26. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in HDL cholesterol [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of HDL cholesterol.

  27. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in low-density lipoprotein (LDL) cholesterol [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of LDL cholesterol.

  28. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in very low-density lipoprotein (VLDL) cholesterol [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of VLDL.

  29. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Ratio to baseline in free fatty acids [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    Measured as ratio of free fatty acids.

  30. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Short Form (SF)-36v score- Physical component summary score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    SF-36v2 measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 acute scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an standard deviation of 10. Physical component summary score range from 6.1 to 79.7, with higher scores indicating better functional health and well-being.

  31. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in SF-36v2 score- Mental component summary score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    SF-36v2 measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 acute scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an standard deviation of 10. Mental component summary score range from -3.8 to 78.7, with higher scores indicating better functional health and well-being.

  32. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    DTSQc measures treatment satisfaction and diabetes-specific quality of life (QoL). The measure consists of 8 items yielding 1 global score and 2 single item scores. Total treatment satisfaction scores range from 0-36, with higher scores indicating greater satisfaction; the perceived frequency of hyperglycemia/hypoglycemia items are scored separately, with lower scores indicating better perceived blood glucose control.

  33. CagriSema versus semaglutide (2.4 mg/2.4 mg versus 2.4 mg and 1.0 mg/1.0 mg vs 1.0 mg): Change in Treatment Related Impact Measure for Diabetes (TRIM-D) score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
    TRIM-D measures impact of diabetes treatment. The measure consists of 28 items yielding 5 domain scores and a total score. The scores were transformed to a 0-100 scale with higher scores indicating a better health state.

  34. CagriSema (2.4 mg/2.4 mg and 1.0 mg/1.0 mg) versus semaglutide (2.4 mg and 1.0 mg), placebo and cagrilintide 2.4 mg: Number of treatment emergent adverse events (TEAEs) [ Time Frame: From baseline (week 0) to end of study (week 75) ]
    Measured as count of events.

  35. CagriSema (2.4 mg/2.4 mg and 1.0 mg/1.0 mg) versus semaglutide (2.4 mg and 1.0 mg), placebo and cagrilintide 2.4 mg: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) [ Time Frame: From baseline (week 0) to end of study (week 75) ]
    Measured as count of episodes.

  36. CagriSema (2.4 mg/2.4 mg and 1.0 mg/1.0 mg) versus semaglutide (2.4 mg and 1.0 mg), placebo and cagrilintide 2.4 mg: Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline (week 0) to end of study (week 75) ]
    Measured as count of episodes. Hypoglycaemia episodes (level 3) are the episodes associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female.
  • Age 18 years or above at the time of signing the informed consent.
  • Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening.
  • Stable daily dose(s) greater than or equal to 90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator: metformin with or without Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors.
  • Glycated haemoglobin (HbA1c) 7.0-10.5 percent (53-91 millimoles per mole [mmol/mol]) (both inclusive) as determined by central laboratory at screening.
  • Body Mass Index (BMI) greater than or equal to 25 kilogram per square metre ( 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:

  • Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square metre (mL/min/1.73 m^2) as determined by central laboratory at screening.
  • 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 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06065540


Contacts
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Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Transparency (dept. 2834) Novo Nordisk A/S
More Information
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT06065540    
Other Study ID Numbers: NN9388-4896
U1111-1283-0427 ( Other Identifier: World Health Organization (WHO) )
2022-502678-18 ( EudraCT Number )
First Posted: October 4, 2023    Key Record Dates
Last Update Posted: May 14, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Semaglutide
Glucagon-Like Peptide-1 Receptor Agonists
Hypoglycemic Agents
Physiological Effects of Drugs