Research Study to Look at How Well Cagrilintide Together With Semaglutide Works in People With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT04982575
• Recruitment Status: Completed
• First Posted: July 29, 2021
• Results First Posted: July 27, 2023
• Last Update Posted: July 27, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

This study looks at how well a new medicine called cagrilintide works together with semaglutide on blood sugar levels in people with type 2 diabetes compared to cagrilintide alone or semaglutide alone.

Before a new medicine can be prescribed to people it needs to be tested to see if it is safe and effective.

Participants will either get cagrilintide and semaglutide together or cagrilintide and a dummy medicine or semaglutide and a dummy medicine. Which treatment participants get is decided by chance.

A dummy medicine (placebo) looks like the study medicine but does not contain any active medicine. The dummy medicine is in the study to see if the study medicine works as expected.

Participants will get 2 injections per week on the same day. Participants will take the study medicine with a pen. A pen is a medical tool with a needle used for injections under the skin. The study doctor or staff will show how.

The study will last for about 39 weeks. Participants will have 12 visits at the clinic and 5 phone calls with the study doctor.

At 6 of the clinic visits participants must not eat and drink for 8 hours before the visit (water is allowed).

Women who can become pregnant cannot take part in this study. Only women that are surgically sterilised or post-menopausal are allowed to participate in this study Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: Semaglutide 2.4 mg; Drug: Cagrilintide 2.4 mg; Drug: Placebo (semaglutide); Drug: Placebo (cagrilintide)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Co-administration of Cagrilintide s.c. 2.4 mg and Semaglutide s.c. 2.4 mg Once Weekly in Subjects With Type 2 Diabetes
• Actual Study Start Date: August 2, 2021
• Actual Primary Completion Date: July 7, 2022
• Actual Study Completion Date: July 7, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cagrilintide 2.4 mg and semaglutide 2.4 mg; Participants will receive cagrilintide and semaglutide once a week as injections for 32 weeks.	Drug: Semaglutide 2.4 mg; Semaglutide administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks; Drug: Cagrilintide 2.4 mg; Cagrilintide administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks
Active Comparator: Cagrilintide 2.4 mg and placebo (semaglutide); Participants will receive cagrilintide and placebo (semaglutide) once a week as injections for 32 weeks	Drug: Cagrilintide 2.4 mg; Cagrilintide administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks; Drug: Placebo (semaglutide); Placebo (semaglutide) administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks
Active Comparator: Semaglutide 2.4 mg and Placebo (cagrilintide); Participants will receive semaglutide and placebo (cagrilintide) once a week as injections for 32 weeks	Drug: Semaglutide 2.4 mg; Semaglutide administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks; Drug: Placebo (cagrilintide); Placebo (cagrilintide) administered s.c. (subcutaneously, under the skin) once weekly. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 32 weeks

Outcome Measures

Primary Outcome Measures :

1. Change in Glycated Haemoglobin (HbA1c): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Semaglutide 2.4 mg + Placebo (Cagrilintide) [ Time Frame: Week 0, Week 32 ]
   Change in HbA1c from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site. The on-treatment without rescue medication period is a subset of the 'on-treatment' observation period and represents the time period where subjects are considered exposed to trial product but have not initiated any rescue medications.

Secondary Outcome Measures :

1. Change in Glycated Haemoglobin (HbA1c): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Cagrilintide 2.4 mg + Placebo (Semaglutide) [ Time Frame: Week 0, Week 32 ]
   Change in HbA1c from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
2. Percentage Change in Body Weight: Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Semaglutide 2.4 mg + Placebo (Cagrilintide) [ Time Frame: Week 0, Week 32 ]
   Percenatge change in body weight from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
3. Change in Body Weight (Kilogram): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Semaglutide 2.4 mg + Placebo (Cagrilintide) [ Time Frame: Week 0, Week 32 ]
   Change in body weight from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
4. Change in Fasting Plasma Glucose (FPG): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Semaglutide 2.4 mg + Placebo (Cagrilintide) [ Time Frame: Week 0, Week 32 ]
   Change in FPG from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
5. CGM: Change in Mean Glucose: Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Cagrilintide 2.4 mg + Placebo (Semaglutide) [ Time Frame: Week 0, Week 32 ]
   Change in mean glucose from baslline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
6. Percentage of Time Above Range (TAR) Greater Than 10.0 mmol/L (Greater Than 180 mg/dL) Measured Using CGM (Continuous Glucose Monitoring): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Cagrilintide 2.4 mg + Placebo (Semaglutide) [ Time Frame: At week 32 ]
   Percentage of TAR greater than 10.0 mmol/L (greater than 180 mg/dL) at week 32 is presented. The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range greater than 10.0 mmol/L (greater than 180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
7. Percentage of Time in Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) Measured Using CGM (Continuous Glucose Monitoring): Cagrilintide 2.4 mg + Semaglutide 2.4 mg Versus Cagrilintide 2.4 mg + Placebo (Semaglutide) [ Time Frame: At week 32 ]
   Percentage of TIR 3.9-10.0 mmol/L (70-180 mg/dL) at week 32 is presented. The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site.
8. Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From baseline (week 0) to week 37 ]
   An adverse event (AE) is any untoward medical occurrence in a clinical trial participants administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. On treatment observation period starts at the date of first dose of trial product and ends at the first date of any of the following; the date of last dose of trial product +35 days for AEs and hypoglycaemic episodes/+ 14 days for other endpoints; the end-date for the 'in-trial' observation period.
9. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0mmol/L (54mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) [ Time Frame: From baseline (week 0) to week 37 ]
   Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 37 are presented. On treatment observation period starts at the date of first dose of trial product and ends at the first date of any of the following; the date of last dose of trial product +35 days for AEs and hypoglycaemic episodes/+ 14 days for other endpoints; the end-date for the 'in-trial' observation period.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Female of non-childbearing potential or male
• Age above or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) greater than or equal to 27.0 kg/m^2
• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening
• Glycated haemoglobin (HbA1c) of 7.5-10.0% (58-86 mmol/mol) (both inclusive) as assessed by central laboratory at screening
• Stable daily dose(s) ≥ 90 days before screening of the following antidiabetic drug(s) or combination regimen(s) at maximum tolerated or effective dose as judged by the investigator: metformin with or without Sodium-glucose co-transporter-2 (SGLT2) inhibitor

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
• Renal impairment with estimated Glomerular Filtration Rate (eGFR) below 60 ml/min/1.73m^2 by central laboratory at 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

Contacts and Locations

Locations

United States, Alabama

Novo Nordisk Investigational Site

Birmingham, Alabama, United States, 35294

United States, California

Novo Nordisk Investigational Site

Los Alamitos, California, United States, 90720

Novo Nordisk Investigational Site

Los Angeles, California, United States, 90057

Novo Nordisk Investigational Site

Spring Valley, California, United States, 91978

United States, Colorado

Novo Nordisk Investigational Site

Golden, Colorado, United States, 80401

United States, Florida

Novo Nordisk Investigational Site

Orlando, Florida, United States, 32825

Novo Nordisk Investigational Site

Plantation, Florida, United States, 33324

United States, Hawaii

Novo Nordisk Investigational Site

Honolulu, Hawaii, United States, 96814

United States, Illinois

Novo Nordisk Investigational Site

Gillespie, Illinois, United States, 62033

United States, Maryland

Novo Nordisk Investigational Site

Oxon Hill, Maryland, United States, 20745

United States, North Carolina

Novo Nordisk Investigational Site

Greensboro, North Carolina, United States, 27408

Novo Nordisk Investigational Site

Wilmington, North Carolina, United States, 28401

United States, North Dakota

Novo Nordisk Investigational Site

Fargo, North Dakota, United States, 58104

United States, Tennessee

Novo Nordisk Investigational Site

Kingsport, Tennessee, United States, 37660

United States, Texas

Novo Nordisk Investigational Site

Dallas, Texas, United States, 75230

Novo Nordisk Investigational Site

Houston, Texas, United States, 77079

Novo Nordisk Investigational Site

Longview, Texas, United States, 75605

United States, Washington

Novo Nordisk Investigational Site

Olympia, Washington, United States, 98502

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

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

  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:

Study Protocol  [PDF] June 16, 2021

Statistical Analysis Plan  [PDF] March 12, 2022

More Information

Publications:

Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, Mathieu C, Pedersen SD, Davies M. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023 Aug 26;402(10403):720-730. doi: 10.1016/S0140-6736(23)01163-7. Epub 2023 Jun 23.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04982575
• Other Study ID Numbers: NN9838-4862
• First Posted: July 29, 2021
• Results First Posted: July 27, 2023
• Last Update Posted: July 27, 2023
• Last Verified: July 2023

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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