A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight (REDEFINE 2)

• ClinicalTrials.gov Identifier: NCT05394519
• Recruitment Status: Active, not recruiting
• First Posted: May 27, 2022
• Last Update Posted: May 16, 2024
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: May 24, 2022
• First Posted Date: May 27, 2022
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: February 1, 2023
• Estimated Primary Completion Date: December 11, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 24, 2023)

• Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in percentage (%).
• Achievement of greater than or equal to (≥) 5% weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.

Original Primary Outcome Measures (submitted: May 24, 2022)

• Relative change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %
• Achievement of greater than or equal to 5% weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant

Current Secondary Outcome Measures (submitted: November 24, 2023)

• Achievement of ≥ 20% weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.
• Relative change in body weight [ Time Frame: From baseline (week 0) to week 20 ]
  Measured in %.
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in centimeter (cm).
• Change in Glycated Haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %-points.
• Change in Systolic Blood Pressure (SBP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in millimeter of mercury (mmHg).
• Change in Impact of Weight on Quality Of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in score points.
• Change in Short Form-36 Version 2.0 Health Survey Acute (SF-36v2 Acute) Physical Functioning score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in score points.
• Change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in kilogram (kg).
• Change in body mass index (BMI) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in kilogram per meter square (kg/m^2).
• Improvement in weight category (BMI, underweight below 18.5, normal weight 18.5 to below 25, overweight 25.0 to below 30, obesity class I 30 to below 35, obesity class II 35 to below 40, obesity class III above 40) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.
• Achievement of HbA1c less than or equal to (≤) 6.5% [ Time Frame: At end of treatment (week 68) ]
  Count of participant.
• Change in Fasting Plasma Glucose (mmol/L) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in millimoles per liter (mmol/L).
• Change in Fasting Plasma Glucose (mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in milligram per deciliter (mg/dL)
• Ratio to baseline in fasting serum insulin [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in ratio.
• Change in Diastolic Blood Pressure (DBP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in mmHg.
• Ratio to baseline in C-reactive protein (CRP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in ratio.
• Ratio to baseline in lipids: Total cholesterol, High-density lipoprotein (HDL) cholesterol, Low-density lipoprotein (LDL) cholesterol, Very low-density lipoprotein (VLDL) cholesterol, Triglycerides and Free fatty acids [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in ratio.
• Change in IWQOL-Lite-CT: Total score, Physical and Psycosocial score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  IWQOL-Lite-CT is a 20-item clinical outcomes assessment (COA) instrument used to assess the impact of body weight changes in obesity studies on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. Score ranges for composite score (physical composite, psychosocial composite and physical function composite) and Total score is 0-100. Higher scores indicate better level of functioning.
• Change in Control of Eating Questionnaire (CoEQ): Craving Control score, Positive Mood score, Craving for Sweet score, Craving for Savoury food score, Hunger score and Satiety score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  CoEQ is a 19-item multidimensional patient-reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), and craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). Higher score represents a greater level of Craving Control.
• Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite-CT Physical Function score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.
• Achievement of at least 3.7-point increase (yes/no) in SF-36v2 Acute Physical Functioning score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.
• Change in IWQOL-Lite-CT Physical Function score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
• Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite -CT Physical Function score for subgroup [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant.
• Continuous glucose monitoring: Change in mean glucose (mmol/L) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in mmol/L.
• Continuous glucose monitoring: Change in mean glucose (mg/L) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in mg/L.
• CGM: Change in time above range (TAR) >10.0 mmol/L (>180 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %-points.
• CGM: Change in time in range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %-points.
• CGM: Change in time above high range (TAHR) >13.9 mmol/L (>250 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %-points.
• CGM: Change in time in tight range (TITR) 3.9-7.8 mmol/L (71-140 mg/dL) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in %-points.
• CGM: Within-day glycaemic variability (% CV) [ Time Frame: At end of treatment (week 68) ]
  Measured in %.
• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From baseline (week 0) to end of study (week 75) ]
  Count of events.
• Number of Treatment Emergent Serious adverse events (TESAEs) [ Time Frame: From baseline (week 0) to end of study (week 75) ]
  Count of events.
• 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) ]
  Count of episodes.
• Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold [ Time Frame: From baseline (week 0) to end of study (week 75) ]
  Count of episodes.

Original Secondary Outcome Measures (submitted: May 24, 2022)

• Achievement of ≥ 20% weight reduction [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Count of participant
• Relative change in body weight [ Time Frame: From baseline (week 0) to week 20 ]
  Measured in %
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in cm
• Change in Glycated Haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  %-points
• Change in Systolic Blood Pressure (SBP) [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Measured in mmHg
• Change in Quality Of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Score points
• Change in Short Form-36 Version 2.0 (SF-36v2) Physical Functioning score [ Time Frame: From baseline (week 0) to end of treatment (week 68) ]
  Score points

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight
• Official Title: Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema s.c. 2.4 mg/2.4 mg) Once-weekly in Participants With Overweight or Obesity and Type 2 Diabetes

Brief Summary

This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight. Participants will either get CagriSema or a dummy medicine. Which treatment they get is decided by chance.

The study will last for about 1½ years. Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Overweight
• Obesity
• Type 2 Diabetes Mellitus

Intervention

• Drug: Cagrilintide
  Cagrilintide administered subcutaneously (s.c., under the skin) once-weekly
• Drug: Semaglutide
  Semaglutide administered subcutaneously (s.c., under the skin) once-weekly
• Drug: Placebo cagrilintide
  Placebo cagrilintide administered subcutaneously (s.c., under the skin) once-weekly
• Drug: Placebo semaglutide
  Placebo semaglutide administered subcutaneously (s.c., under the skin) once-weekly

Study Arms

• Experimental: CagriSema
  Cagrilintide + semaglutide once weekly
  Interventions:

  • Drug: Cagrilintide
  • Drug: Semaglutide
• Placebo Comparator: Placebo
  Placebo cagrilintide + semaglutide once weekly
  Interventions:

  • Drug: Placebo cagrilintide
  • Drug: Placebo semaglutide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 24, 2022): 1200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 29, 2025
• Estimated Primary Completion Date: December 11, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female
• Age above or equal to 18 years at the time of signing informed consent
• BMI greather than or equal to 27.0 kg/m^2
• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening
• Treatment with either lifestyle intervention, or treatment with 1-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), thiazolidinediones, or sulphonylureas (SU)s as a single agent or in combination) according to local label
• Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and dosing frequency) for at least 90 days before screening
• HbA1c 7%-10% (53-86 mmol/mol) (both inclusive) as measured by the central laboratory at screening

Exclusion Criteria:

• Clinically significant or severe hypoglycaemia within 6 months before screening or history of hypoglycaemia unawareness
• Renal impairment with estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2, as measured by the 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, Germany, Hungary, India, Ireland, Japan, Malaysia, Poland, Puerto Rico, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT05394519
• Other Study ID Numbers: NN9838-4609; U1111-1267-4287 ( Other Identifier: World Health Organization (WHO) ); 2021-005121-24 ( EudraCT Number ); jRCT2031220671 ( Registry Identifier: jRCT (Japan) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Novo Nordisk A/S
• Verification Date: May 2024