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 Once-daily Basal Insulin With or Without Metformin

Type 2 Diabetes Clinical Trial

— REIMAGINE 3  

Official title:

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 as Add on to Once-daily Basal Insulin With or Without Metformin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06323161
• Other study ID #: NN9388-7637
• Secondary ID: U1111-1283-07542
• Status: Recruiting
• Phase: Phase 3
• Start date: March 26, 2024
• Est. completion date: November 4, 2025

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at how much CagriSema helps people 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. Participant will get either CagriSema or "dummy" medicine and which treatment they get is decided by chance. Participant will take the study medicine together with their current diabetes medicine (once-daily insulin with or without metformin). For each participant, the study will last for about one year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: November 4, 2025
• Est. primary completion date: September 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female.
• Age 18 years or above at the time of signing the informed consent.
• Diagnosed with type 2 diabetes mellitus =180 days before screening.
• On stable once-daily dose of basal insulin (minimum of 0.25 units per kilogram per day (U/kg/day) or 20 U/day) alone or in combination with metformin (at effective or maximum tolerated dose as judged by the investigator) for 90 days prior to screening.
• 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 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 (eGFR) less than 30 milliliters 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 other than stated in the inclusion criteria within 90 days before screening.
• 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.
• Known hypoglycaemia unawareness as indicated by the investigator according to Clarke's questionnaire question 8.
• Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Cagrilintide
Participants will receive once-weekly cagrilintide subcutaneously.
• Semaglutide
Participants will receive once-weekly semaglutide subcutaneously.
• Placebo
Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously.

Locations

Country	Name	City	State
China	Chinese People's Liberation Army General Hospital	Beijing	Beijing
China	Jinan Central Hospital	Ji'nan	Shandong
China	The Second Affiliated Hospital of Nanjing Medical University_Nanjing	Nanjing	Jiangsu
China	Shanghai Pudong New Area People's Hospital	Shanghai	Shanghai
China	The Affiliated Hospital of Jiangsu University_Zhenjiang	Zhenjiang	Jiangsu
Japan	Kumanomae Nishimura Internal Medical Clinic	Arakawa-ku, Tokyo
Japan	Akaicho Clinic	Chiba-shi, Chiba
Japan	Futata Tetsuhiro Clinic Meinohama	Fukuoka-shi, Fukuoka
Japan	Kunisaki Makoto Clinic	Fukuoka-shi, Fukuoka
Japan	Sasaki Hospital Internal Medicine	Hokkaido
Japan	Naka Kinen Clinic	Ibaraki
Japan	H.E.C Science Clinic	Kanagawa
Japan	Minami Akatsuka Clinic	Mito-shi, Ibaraki
Japan	Manda Memorial Hospital	Sapporo-shi, Hokkaido	Hokkaido, Japan
Japan	Fukuwa Clinic	Tokyo
Japan	Kato Clinic of Internal Medicine	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Tokyo
Japan	Tsuruma Kaneshiro Diabetes Clinic	Yamato-shi	Kanagawa
Serbia	Healthcare centre Zvezdara	Belgrade	RS
Serbia	Healthcare centre Kragujevac	Kragujevac	RS
Serbia	Healthcare centre Nis	Nis	RS
Serbia	University Clinical Centre Nis	Nis	RS
Serbia	Policlinic for diabetes	Zajecar
Slovakia	MOMED, s.r.o	Kralovsky Chlmec
Slovakia	DIA - KONTROL s.r.o.	Levice
Slovakia	SIN AZUCAR s.r.o.	Malacky
Slovakia	ENRIN, s.r.o.	Rimavska Sobota
Slovakia	LUDIA, s.r.o.	Spisska Nova Ves
South Africa	Vuyo Clinical Research	Bloemfontein	Free State
South Africa	Ashmed Medi-Centre	Cape Town	Western Cape
South Africa	Lenasia Clinical Trial Centre	Lenasia	Gauteng
South Africa	Clinical Trial Systems (CTC)	Pretoria	Gauteng
South Africa	Prinshof Medical Campus	Pretoria	Gauteng
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Elite Research Center	Flint	Michigan
United States	PlanIt Research, PLLC	Houston	Texas
United States	Synergy Groups Medical	Houston	Texas
United States	Palm Research Center Inc.	Las Vegas	Nevada
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Solaris Clinical Research	Meridian	Idaho
United States	Bioclinical Research Alliance	Miami	Florida
United States	Clinical Research Associates	Nashville	Tennessee
United States	TPMG Clinical Research	Newport News	Virginia
United States	Alliance for Multispec Res	Newton	Kansas
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Iowa Diab & Endo Res Center	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  China,  Japan,  Serbia,  Slovakia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycated Haemoglobin (HbA1c)	Measured in percentage (%)- points.	From baseline (week 0) to end of treatment (week 40)
Secondary	Relative Change in Body Weight	Measured in percentage (%).	From baseline (week 0) to end of treatment (week 40)
Secondary	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)
Secondary	Number of Participants Who Achieve =15% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Participants Who Achieve HbA1c Target Values of Less than (<) 7.0% (<53 millimole per mole [mmol/mol])	Measured as count of participants.	At end of treatment (week 40)
Secondary	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)
Secondary	Change in Fasting Plasma Glucose (FPG)	Measured as millimole per liter (mmol/L).	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Insulin Dose	Measured in units (u).	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Participants Who Achieve Insulin Dose Equal to (=) 0 Units	Measured as count of participants.	At end of treatment (week 40)
Secondary	Change in 7-point Self-measured Plasma Glucose (SMPG) Profiles: Mean 7-point profile and Mean postprandial increment (over all meals)	Measured in mmol/L.	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Participants Who Achieve =5% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Participants Who Achieve =20% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Waist Circumference	Measured in centimeter (cm).	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Systolic Blood Pressure (SBP)	Measured in millimeter of mercury (mmHg).	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Diastolic Blood Pressure (DBP)	Measured in mmHg.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in High Sensitivity C-reactive Protein (hsCRP)	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Non-high Density Lipoprotein (Non-HDL) Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Triglycerides	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Low-Density Lipoprotein (LDL) Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Very Low-Density Lipoprotein (VLDL) cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: HDL Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Total Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Ratio to Baseline in Lipids: Free Fatty Acids	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Short Form-36 Version 2.0 Health Survey (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)
Secondary	Change in SF-36v2: 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)
Secondary	Change in SF-36v2: Mental Component Summary Core	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)
Secondary	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)
Secondary	Change in Leptin	Measured in nanogram per milliliter (ng/mL).	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Soluble Leptin Receptor	Measured in ng/mL.	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	Measured as count of events.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Secondary	Number of Clinically Significant Hypoglycaemic Episodes (level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose Meter)	Measured as count of episodes.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Secondary	Number of Clinically Significant Hypoglycaemic Episodes (level 3)	Measured as count of episodes. Hypoglycaemic episodes (level 3) is hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold.	From baseline (week 0) to end of treatment +7 weeks (week 47)