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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,734
- 试验地点
- 796
- 主要终点
- CagriSema (dose 1) versus semaglutide (dose 1): Change in glycated haemoglobin (HbA1c)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female (sex at birth).
- •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.
排除标准
- •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 an eye examination performed within 90 days before screening or in the period between screening and randomisation.
研究组 & 干预措施
Semaglutide Dose 1
Participants will receive once-weekly s.c injection of semaglutide dose 1 for 68 weeks.
干预措施: Semaglutide (Drug)
Cagrilintide Dose 1
Participants will receive once-weekly s.c injection of cagrilintide dose 1 for 68 weeks.
干预措施: Cagrilintide (Drug)
Placebo Dose 2
Participants will receive once-weekly s.c injection of placebo matched to cagrilintide dose 2 and semaglutide dose 2 for 68 weeks.
干预措施: Placebo semaglutide (Drug)
Placebo Dose 1
Participants will receive once-weekly s.c injection of placebo matched to cagrilintide dose 1 and semaglutide dose 1 for 68 weeks.
干预措施: Placebo cagrilintide (Drug)
CagriSema Dose 1
Participants will receive once-weekly subcutaneous (s.c) injections of cagrilintide dose 1 and semaglutide dose 1 for 68 weeks.
干预措施: Semaglutide (Drug)
Semaglutide Dose 2
Participants will receive once-weekly s.c injection of semaglutide dose 2 for 68 weeks.
干预措施: Semaglutide (Drug)
Placebo Dose 1
Participants will receive once-weekly s.c injection of placebo matched to cagrilintide dose 1 and semaglutide dose 1 for 68 weeks.
干预措施: Placebo semaglutide (Drug)
CagriSema Dose 1
Participants will receive once-weekly subcutaneous (s.c) injections of cagrilintide dose 1 and semaglutide dose 1 for 68 weeks.
干预措施: Cagrilintide (Drug)
CagriSema Dose 2
Participants will receive once-weekly s.c injections of cagrilintide dose 2 and semaglutide dose 2 for 68 weeks.
干预措施: Cagrilintide (Drug)
Placebo Dose 2
Participants will receive once-weekly s.c injection of placebo matched to cagrilintide dose 2 and semaglutide dose 2 for 68 weeks.
干预措施: Placebo cagrilintide (Drug)
CagriSema Dose 2
Participants will receive once-weekly s.c injections of cagrilintide dose 2 and semaglutide dose 2 for 68 weeks.
干预措施: Semaglutide (Drug)
结局指标
主要结局
CagriSema (dose 1) versus semaglutide (dose 1): Change in glycated haemoglobin (HbA1c)
时间窗: From baseline (week 0) to end of treatment (week 68)
Measured in percentage-points.
次要结局
- CagriSema versus cagrilintide: Change in HbA1c(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus cagrilintide: Relative change in body weight(From baseline (week 0) to end of treatment (week 68))
- CagriSema (dose 1) versus semaglutide (dose 2): Change in HbA1c(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Relative change in body weight(From baseline (week 0) to end of treatment (week 68))
- Cagrilintide versus placebo: Change in HbA1c(From baseline (week 0) to end of treatment (week 68))
- Cagrilintide versus placebo: Relative change in body weight(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of greater than or equal to (>=) 10 percent (%) weight reduction(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of >= 15 % weight reduction(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of >= 20 % weight reduction(From baseline (week 0) to end of treatment (week 68))
- CagriSema (pooled doses) versus semaglutide (pooled doses): Continuous Glucose Monitoring (CGM) - Change in Time in Range (TIR) 3.9-10.0 millimoles per litre (mmol/L) (70-180 milligrams per decilitre [mg/dL])(From baseline (week -3) to end of treatment (week 68))
- CagriSema versus semaglutide: CGM - Change in time in Tight Target Range (TITR) 3.9-7.8 (mmol/L) (70-140 mg/dL)(From baseline (week -3) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Systolic Blood Pressure (SBP)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in triglycerides(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in non-High Density Lipoprotein (HDL) cholesterols(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: CGM - Change in Time In Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL)(From baseline (week -3) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in high sensitivity C-Reactive Protein (hsCRP)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Fasting Plasma Glucose (FPG)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol])(At end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of HbA1c target values of less than or equal to (≤)6.5% (≤48 mmol/mol)(At end of treatment (week 68))
- CagriSema versus semaglutide: CGM - Change in time above range, >10.0 mmol/L (>180 mg/dL)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: CGM - Change in time above range, >13.9 mmol/L (>250 mg/dL)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: CGM - Within-day glycaemic variability (% coefficient of variation [CV])(At end of treatment (week 68))
- CagriSema versus semaglutide: Achievement of ≥ 5 % weight reduction(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in waist circumference(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Diastolic Blood Pressure (DBP)(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in total cholesterol(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in HDL cholesterol(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in low-density lipoprotein (LDL) cholesterol(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in very low-density lipoprotein (VLDL) cholesterol(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Ratio to baseline in free fatty acids(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Short Form (SF)-36v score- Physical component summary score(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in SF-36v2 score- Mental component summary score(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide: Change in Treatment Related Impact Measure for Diabetes (TRIM-D) score(From baseline (week 0) to end of treatment (week 68))
- CagriSema versus semaglutide, placebo and cagrilintide: Number of treatment emergent adverse events (TEAEs)(From baseline (week 0) to end of study (week 75))
- CagriSema versus semaglutide: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)(From baseline (week 0) to end of study (week 75))
- CagriSema versus semaglutide: Number of severe hypoglycaemic episodes (level 3)(From baseline (week 0) to end of study (week 75))