A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weight

Novo Nordisk

Status and phase: Enrolling; Phase 3

Conditions: Overweight; Obesity

Treatments: Drug: Placebo cagrilintide; Drug: Cagrilintide; Drug: Placebo semaglutide; Drug: Semaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT07253285

U1111-1299-4751 (Other Identifier)

NN9838-4968

2023-509176-42 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 460 estimated patients

Sex: All

Ages: 8 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 exclusion criteria also apply
• HbA1c greater than or equal to 6.5% (48 mmol/mol) as measured by the central laboratory at screening.
• Treatment with glucose-lowering agent(s) prescribed for the indication of diabetes or pre-diabetes within 90 days before screening.

For participants with T2D at screening the following exclusion criteria also apply

• Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire.
• Recurrent severe hypoglycaemic episodes within 1 year before screening, as judged by the investigator.
• Positive insulinoma associated protein-2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.
• Treatment with any medication for the indication of diabetes other than those 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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460 participants in 4 patient groups, including a placebo group

CagriSema

Experimental group

Description:

Participants will receive once weekly subcutaneous (s.c.) dose of CagriSema (cagrilintide and semaglutide) in a dose escalation regimen in the main phase for up to 16 weeks and maintained for 52 weeks and further continue to receive the same dose or maximum tolerated dose (MTD) in the open-label extension phase for up to 156 weeks.

Treatment:

Drug: Semaglutide

Drug: Placebo semaglutide

Drug: Placebo cagrilintide

Drug: Cagrilintide

Semaglutide

Experimental group

Description:

Participants will receive once weekly s.c. dose of semaglutide in a dose escalation regimen in the main phase for up to 16 weeks and maintained for 52 weeks.

Treatment:

Drug: Semaglutide

Drug: Placebo semaglutide

Cagrilintide

Experimental group

Description:

Participants will receive once weekly s.c. dose of cagrilintide in a dose escalation regimen in the main phase for up to 16 weeks and maintained for 52 weeks, further continue to receive the same dose as the dose escalation regimen or MTD in the open-label extension phase for up to 156 weeks.

Treatment:

Drug: Placebo cagrilintide

Drug: Cagrilintide

Placebo

Placebo Comparator group

Description:

Participants will receive once weekly s.c. dose of placebo matched to cagrilintide/semaglutide in a dose escalation regimen in the main phase for up to 16 weeks and maintained for 52 weeks. Participants will further continue to receive the same dose escalation regimen as CagriSema for 16 weeks, later continue to receive the same dose or MTD in the open-label extension phase for up to 140 weeks.

Treatment:

Drug: Placebo semaglutide

Drug: Placebo cagrilintide