Overweight, Obesity
Conditions
Brief summary
This study will look at how well CagriSema and cagrilintide help children and adolescents with excess body weight lose weight. The study has 2 parts: main and extension study. In the main study, participants will either get CagriSema (a new study drug), cagrilintide (a new study drug), semaglutide (a drug that doctors can already prescribe to adolescents and adults) or placebo (a placebo looks like the treatment being tested, but doesn't have any active ingredients in it). Which treatment participants will get is decided by chance. Participants who get semaglutide in the main study will not take part in the extension study. If participants take part in the extension study, they will get either CagriSema or cagrilintide in this part of the study. Like all drugs, the study drugs may have side effects. The total time participants will be in the main study is about 1 year and 6 months. If participants take part in the extension study, the total time is about 4 years and 10 months.
Interventions
DRUGCagrilintide
Participants will receive cagrilintide subcutaneously.
DRUGSemaglutide
Participants will receive semaglutide subcutaneously.
Participants will receive placebo matched to cagrilintide subcutaneously.
Participants will receive placebo matched to semaglutide subcutaneously.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures. The main phase of the study is double blinded and followed by an open label extension phase.
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent of parent(s) or legally acceptable representative (LAR) of participant and child assent, as age-appropriate, obtained before any study related activities. Study related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. * The parent(s) or LAR of the child must sign and date the Informed Consent Form (according to local requirements) * The child must sign and date the Child Assent Form or provide oral assent (according to local requirements). * Male or female. * Aged 8 to less than (\<) 18 years at the time of signing the informed consent. * Body mass index (BMI), at screening, corresponding to: * Greater than or equal to (\>=) 95th percentile for children aged 8 to \< 12 years (Tanner stage 1-5) * \>= 95th percentile or \>= 85th percentile with the presence of at least one obesity-related complication including, but not limited to, type 2 diabetes (T2D), hypertension, dyslipidaemia or obstructive sleep apnoea for adolescents aged 12 to \< 18 years (Tanner stage 2-5). * Laboratory parameters, as measured by the central lab at screening, within normal sex- and age-specific ranges of total calcium, phosphate, alkaline phosphatase, parathyroid hormone. * History of at least one unsuccessful effort to lose sufficient body weight after participation in a structured lifestyle modification programme (diet and exercise counselling) for at least 3 months. * Body weight greater than (\>) 45 kilograms (kg) at screening. For participants with T2D at screening the following inclusion criteria also apply * Glycated haemoglobin (HbA1c) less than or equal to (\<=)10.0 percent (%) (86 millimoles per mole \[mmol/mol\]) as measured by central laboratory at screening. * Treatment with lifestyle intervention or treatment with metformin according to local label. * Treatment with metformin should be stable (same dose and dosing frequency) for at least 56 days before screening. Key
Exclusion criteria
* Treatment with any medication prescribed for obesity or weight management within 90 days before screening. * Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: * Liposuction and/or abdominoplasty, if performed \> 1 year before screening. * Adjustable gastric banding, if the band has been removed \> 1 year before screening. * Intragastric balloon, if the balloon has been removed \> 1 year before screening. * Duodenal-jejunal bypass liner (e.g., Endobarrier), if the sleeve has been removed \>1 year before screening. * Uncontrolled thyroid disease. * Endocrine, hypothalamic, or syndromic obesity. * A self-reported (or by parent(s)/LAR, where applicable) change in body weight \> 5 % within 90 days before screening irrespective of medical records. * Type 1 diabetes or monogenic diabetes. For participants without T2D at screening the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative change in body mass index (BMI) | Baseline (week 0), week 68 | Measured in percentage (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change in body weight | Baseline (week 0), week 68 | Measured in %. |
| Change in BMI Standard Deviation Score (SDS) | Baseline (week 0), week 68 | Measured as SDS score. |
| Relative change in BMI | Baseline (week 0), week 68 and week 224 | Measured in %. |
| Number of participants in weight category reduction | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved greater than or equal to (>=) 5 percent (%) reduction of body weight (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=10% reduction of body weight (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=15% reduction of body weight (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=20% reduction of body weight (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=25% reduction of body weight (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=5% reduction of BMI (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=10% reduction of BMI (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=15% reduction of BMI (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=20% reduction of BMI (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved >=25% reduction of BMI (yes/no) | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who achieved normal BMI | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants who shifted from obese to non-obese BMI class | Baseline (week 0), week 68 | Measured as count of participants. |
| Change in waist circumference | Baseline (week 0), week 68 and week 224 | Measured in centimeter (cm). |
| Change in waist-to-height ratio | Baseline (week 0), week 68 | Measured as ratio. |
| Absolute change in total fat mass by dual energy X-ray absorption (DXA) | Baseline (week 0), week 68 | Measured in kilograms (kg). |
| Relative to baseline change in total fat mass by DXA | Baseline (week 0), week 68 | Measured in %. |
| Relative to total body mass change in total fat mass by DXA | Baseline (week 0), week 68 | Measured in % points. |
| Absolute change in visceral fat mass by DXA | Baseline (week 0), week 68 | Measured in kg. |
| Relative to baseline change in visceral fat mass by DXA | Baseline (week 0), week 68 | Measured in %. |
| Relative to total body mass change in visceral fat mass by DXA | Baseline (week 0), week 68 | Measured in % points. |
| Absolute change in lean body mass by DXA | Baseline (week 0), week 68 | Measured in kg. |
| Relative to total body mass change in lean body mass by DXA | Baseline (week 0), week 68 | Measured in % points. |
| Absolute change in total (neck-to-knee) muscle and fat volumes by Magnetic Resonance Imaging (MRI) - total muscle and total fat | Baseline (week 0), week 68 and week 224 | Measured in liters (L). |
| Relative to baseline change in total (neck-to-knee) muscle and fat volumes by MRI - total muscle and total fat | Baseline (week 0), week 68 and week 224 | Measured in %. |
| Change in ectopic fat content by MRI - liver fat MRI-Proton Density Fat Fraction (MRI-PDFF), pancreatic fat, kidney fat and thigh muscle fat infiltration | Baseline (week 0), week 68 and week 224 | Measured in % points. |
| Absolute change in abdominal fat volumes by MRI - subcutaneous fat and visceral fat | Baseline (week 0), week 68 and week 224 | Measured in liters. |
| Relative to baseline change in abdominal fat volumes by MRI - subcutaneous fat and visceral fat | Baseline (week 0), week 68 and week 224 | Measured in %. |
| Absolute change in thigh muscle and fat volumes by MRI - thigh fat free muscle and thigh subcutaneous fat | Baseline (week 0), week 68 and week 224 | Measured in liters. |
| Relative to baseline change in thigh muscle and fat volumes by MRI - thigh fat free muscle and thigh subcutaneous fat | Baseline (week 0), week 68 and week 224 | Measured in %. |
| Ratio to baseline in liver stiffness measured by Magnetic Resonance Elastography (MRE) | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Change in BMI percentage of the 95th percentile | Baseline (week 0), week 68 | Measured in % points. |
| Ratio to baseline highly sensitive C-reactive protein (hs-CRP) | Baseline (week 0), week 68 | Measured as ratio. |
| Ratio to baseline in lipids: Total cholesterol | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Ratio to baseline in lipids: High Density Lipoprotein (HDL) cholesterol | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Ratio to baseline in lipids: Low Density Lipoprotein (LDL) cholesterol | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Ratio to baseline in lipids: Very Low Density Lipoprotein (VLDL) cholesterol | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Ratio to baseline in lipids: Triglycerides | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Ratio to baseline in lipids: Non-HDL cholesterol | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Change in Alanine Transaminase (ALT) | Baseline (week 0), week 68 and week 224 | Measured in Units per Liter (U/L). |
| Change in systolic blood pressure | Baseline (week 0), week 68 and week 224 | Measured in millimeters of mercury (mmHg). |
| Change in diastolic blood pressure | Baseline (week 0), week 68 and week 224 | Measured in mmHg. |
| Ratio to baseline in liver stiffness measured by ultrasonographic methods | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Change in glycated haemoglobin (HbA1c) (% points) | Baseline (week 0), week 68 and week 224 | Measured in % points. |
| Change in HbA1c (millimoles per mole [mmol/mol]) | Baseline (week 0), week 68 and week 224 | Measured in mmol/mol. |
| Change in Fasting Plasma Glucose (FPG) (millimoles per liter [mmol/L]) | Baseline (week 0), week 68 | Measured in mmol/L. |
| Change in FPG (milligrams per deciliter [mg/dL]) | Baseline (week 0), week 68 | Measured in mg/dL. |
| Ratio to baseline in fasting serum insulin | Baseline (week 0), week 68 and week 224 | Measured as ratio. |
| Number of participants with prediabetes who achieved HbA1c less than (<) 5.7% (defined as 5.7 % less than or equal to [<=] HbA1c <6.5 %) at baseline | At week 68 | Measured as count of participants. |
| Number of participants with normoglycemia (defined as HbA1c < 5.7 %) at baseline, development of HbA1c greater than or equal to (>=) 5.7 % | At week 68 | Measured as count of participants. |
| Number of participants with prediabetes (5.7 % <= HbA1c < 6.5 %) at baseline, development of HbA1c >= 6.5% | At week 68 | Measured as count of participants. |
| Number of participants with HbA1c >=6.5% at baseline, achievement of HbA1c <6.5% | At week 68 | Measured as count of participants. |
| Number of participants taking glucose lowering medication at baseline, stop or decrease | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants taking antihypertensive medication at baseline, stop or decrease | Baseline (week 0), week 68 | Measured as count of participants. |
| Number of participants taking lipid lowering medication at baseline, stop or decrease | Baseline (week 0), week 68 | Measured as count of participants. |
| Impact of Weight on Quality of Life-Kids (IWQOL Kids) - Physical comfort domain score | Baseline (week 0), week 68 and week 224 | Measured as score points. IWQOL-Kids measures weight-related quality of life in adolescents (ages 11-19 years) but will be administered to all study participants. The measure consists of 27-items yielding 4 sub-scale scores, and 1 total score. Higher scores indicate better weight-related quality of life. Subscale scores (score range): physical comfort (0-100), body esteem (0-100), social life (0-100), family relations (0-100) and total score (0-100). |
| IWQOL Kids - Body esteem domain score | Baseline (week 0), week 68 and week 224 | Measured as score points. IWQOL-Kids measures weight-related quality of life in adolescents (ages 11-19 years) but will be administered to all study participants. The measure consists of 27-items yielding 4 sub-scale scores, and 1 total score. Higher scores indicate better weight-related quality of life. Subscale scores (score range): physical comfort (0-100), body esteem (0-100), social life (0-100), family relations (0-100) and total score (0-100). |
| IWQOL Kids - Social life domain score | Baseline (week 0), week 68 and week 224 | Measured as score points. IWQOL-Kids measures weight-related quality of life in adolescents (ages 11-19 years) but will be administered to all study participants. The measure consists of 27-items yielding 4 sub-scale scores, and 1 total score. Higher scores indicate better weight-related quality of life. Subscale scores (score range): physical comfort (0-100), body esteem (0-100), social life (0-100), family relations (0-100) and total score (0-100). |
| IWQOL Kids - Family-relations score | Baseline (week 0), week 68 and week 224 | Measured as score points. IWQOL-Kids measures weight-related quality of life in adolescents (ages 11-19 years) but will be administered to all study participants. The measure consists of 27-items yielding 4 sub-scale scores, and 1 total score. Higher scores indicate better weight-related quality of life. Subscale scores (score range): physical comfort (0-100), body esteem (0-100), social life (0-100), family relations (0-100) and total score (0-100). |
| IWQOL Kids - Total score | Baseline (week 0), week 68 and week 224 | Measured as score points. IWQOL-Kids measures weight-related quality of life in adolescents (ages 11-19 years) but will be administered to all study participants. The measure consists of 27-items yielding 4 sub-scale scores, and 1 total score. Higher scores indicate better weight-related quality of life. Subscale scores (score range): physical comfort (0-100), body esteem (0-100), social life (0-100), family relations (0-100) and total score (0-100). |
| Control of Eating Questionnaire (COEQ) | Baseline (week 0), week 68 and week 224 | Measured as score points. 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), 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). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control. |
| Change in proteomics-based serum biomarkers including biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) | Baseline (week 0), week 68 and week 224 | Measured as counts. |
| Number of treatment-emergent adverse events (TEAEs) | Baseline (week 0), week 68 and week 224 | Measured as count of events. |
| Number of treatment-emergent serious adverse events (TESAEs) | Baseline (week 0), week 68 and week 224 | Measured as count of events. |
| Number of treatment-emergent hypoglycaemic episodes | Baseline (week 0), week 68 and week 224 | Measured as count of events. |
| Change in pulse rate | Baseline (week 0), week 68 | Measured in beats per minute (beats/min). |
| Change in calcitonin | Baseline (week 0), week 68 | Measured in nanograms per liter (ng/L). |
| Apparent clearance (CL/F) of semaglutide and cagrilintide at steady state | Baseline (week 0), week 68 | Measured in liters per hour (L/h). |
| Average concentration (Cavg) of semaglutide and cagrilintide at steady state | Baseline (week 0), week 68 | Measured in nanomoles per liter (nmol/L). |
| Area under the steady-state concentration-time curves (AUCt) in the dosing interval of semaglutide and cagrilintide | Baseline (week 0), week 68 | Measured in hours nanomoles per liter (h·nmol/L). |
Countries
Australia, Austria, Belgium, Bulgaria, China, Colombia, Croatia, Denmark, Hungary, India, Israel, Italy, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Contacts
CONTACTNovo Nordisk
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed