A Research Study to Compare a New Medicine Oral Semaglutide to a Dummy Medicine in Children and Teenagers With Type 2 Diabetes

Study Overview
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Brief Summary
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This study compares 2 medicines for type 2 diabetes: semaglutide (new medicine) and a dummy medicine (placebo). Semaglutide will be tested to see how well it works compared to the dummy medicine. The study will also test if semaglutide is safe in children and teenagers. Participants will either get semaglutide or the dummy medicine - which one is decided by chance. Participants will take 1 tablet of the study medicine every morning on an empty stomach. They have to wait 30 minutes before they eat, drink or take any other medication by mouth. The study will last for about 1 year and 3 months (66 weeks). Participants will have 12 clinic visits and 8 phone calls with the study doctor. At all 12 clinic visits, participants will have blood samples taken. Participants will also be asked some questions.

Official Title
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Efficacy and Safety of Oral Semaglutide Versus Placebo Both in Combination With Metformin and/or Basal Insulin in Children and Adolescents With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Oral semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent from parent(s) or legally acceptable representative (LAR) and child assent from the subject obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Male or female, aged 10 to below 18 years at the day of randomisation HbA1c 6.5%-11.0% (47-97 mmol/mol) (both inclusive) Diagnosed with type 2 diabetes mellitus according to the American Diabetes Association criteria and treated with: stable metformin dose (stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 56 days or longer prior to screening) or stable metformin dose and a stable dose of basal insulin (stable dose of basal insulin is defined as basal insulin treatment equal to or more than 30 days prior to screening, compared to the dose at screening, dose adjustments of ± 25% are allowed) or stable dose of basal insulin Exclusion Criteria: Diagnosis of type 1 diabetes Maturity onset diabetes of the young (MODY) Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide - max. tolerated dose<br>Participants will receive semaglutide tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise. | Drug: Oral semaglutide<br>* Oral semaglutide treatment for 52 weeks. All participants will be dose-escalated to an individual maximum tolerated dose.<br>|
| Placebo Comparator: Placebo (semaglutide)<br>Participants will receive semaglutide placebo tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise. | Drug: Placebo (semaglutide)<br>* Placebo treatment for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glycosylated haemoglobin (HbA1c) | Percentage point | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose (FPG) | mmol/L | Week 0, week 26 | 
| Change from baseline in body mass index (BMI) standard deviation score (SDS) | SDS | Week 0, week 26 | 
| Change from baseline in glycosylated haemoglobin (HbA1c) | Percentage point | Week 0, week 52 | 
| Change from baseline in FPG | mmol/L | Week 0, week 52 | 
| Change from baseline in body weight | kg | Week 0, week 26 | 
| Change from baseline in body weight | kg | Week 0, week 52 | 
| Relative change from baseline in body weight | Percentage | Week 0, week 26 | 
| Relative change from baseline in body weight | Percentage | Week 0, week 52 | 
| Change from baseline in waist circumference | cm | Week 0, week 26 | 
| Change from baseline in waist circumference | cm | Week 0, week 52 | 
| Change from baseline in BMI SDS | SDS | Week 0, week 52 | 
| BMI percentile (age and gender adjusted) | Percent | Week 0, week 26 | 
| BMI percentile (age and gender adjusted) | Percent | Week 0, week 52 | 
| Change from baseline in systolic blood pressure | mmHg | Week 0, week 26 | 
| Change from baseline in systolic blood pressure | mmHg | Week 0, week 52 | 
| Change from baseline in diastolic blood pressure | mmHg | Week 0, week 26 | 
| Change from baseline in diastolic blood pressure | mmHg | Week 0, week 52 | 
| HbA1c below 7.0% (53 mmol/mol) (yes/no), American Diabetes Association (ADA) target and International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines from 2018 | Count of participants | At week 26 | 
| HbA1c equal to or below 6.5% (48 mmol/mol) (yes/no), American Association of Clinical Endocrinologists (AACE) target | Count of participants | At week 26 | 
| HbA1c below 7.0% (53 mmol/mol) (yes/no), ADA target and ISPAD guidelines from 2018 | Count of participants | At week 52 | 
| HbA1c equal to or below 6.5% (48 mmol/mol) (yes/no), AACE targetat week 26 | Count of participants | At week 52 | 
| Time to additional anti-diabetic medication (to support the treatment policy estimand) | Days | Week 0 - week 52 | 
| Time to rescue medication (to support the hypothetical estimand) | Days | Week 0 - week 52 | 
| Number of treatment-emergent adverse events (TEAEs) during exposure to trial product | Count of events | Week 0 - week 57 | 
| Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes | Count of episodes | From randomisation (week 0) to week 26 | 
| Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes during exposure to trial product | Count of episodes | Week 0 - week 57 | 
| Treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode | Count of participants | From randomisation (week 0) to week 26 | 
| Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode during exposure to trial product | Count of participants | Week 0 - week 57 | 
| Change from baseline in amylase | U/L | Week 0, week 26 | 
| Change from baseline in amylase | U/L | Week 0, week 52 | 
| Change from baseline in lipase | U/L | Week 0, week 26 | 
| Change from baseline in lipase | U/L | Week 0, week 52 | 
| Change from baseline in insulin-like growth factor 1 (IGF-1) | ng/mL | Week 0, week 26 | 
| Change from baseline in insulin-like growth factor 1 (IGF-1) | ng/mL | Week 0, week 52 | 
| Change from baseline in insulin-like growth factor binding protein 3 (IGFBP 3) | ng/mL | Week 0, week 26 | 
| Change from baseline in insulin-like growth factor binding protein 3 (IGFBP 3) | ng/mL | Week 0, week 52 | 
| Change from baseline in calcitonin | pmol/L | Week 0, week 26 | 
| Change from baseline in calcitonin | pmol/L | Week 0, week 52 | 
| Change from baseline in estradiol (for girls) | pmol/L | Week 0, week 26 | 
| Change from baseline in estradiol (for girls) | pmol/L | Week 0, week 52 | 
| Change from baseline in testosterone (for boys) | nmol/L | Week 0, week 26 | 
| Change from baseline in testosterone (for boys) | nmol/L | Week 0, week 52 | 
| Change from baseline in prolactin | mIU/L | Week 0, week 26 | 
| Change from baseline in prolactin | mIU/L | Week 0, week 52 | 
| Change from baseline in thyroid stimulating hormone (TSH/thyrotropin) | mIU/L | Week 0, week 26 | 
| Change from baseline in thyroid stimulating hormone (TSH/thyrotropin) | mIU/L | Week 0, week 52 | 
| Change from baseline in follicle stimulating hormone (FSH) | mIU/mL | Week 0, week 26 | 
| Change from baseline in follicle stimulating hormone (FSH) | mIU/mL | Week 0, week 52 | 
| Change from baseline in luteinizing hormone (LH) | mIU/mL | Week 0, week 26 | 
| Change from baseline in luteinizing hormone (LH) | mIU/mL | Week 0, week 52 | 
| Change from baseline in dehydroepiandrosterone sulfate (DHEAS) | μmol/L | Week 0, week 26 | 
| Change from baseline in dehydroepiandrosterone sulfate (DHEAS) | μmol/L | Week 0, week 52 | 
| Anti-semaglutide antibody status | Count of participants | Week 0 - week 57 | 
| Anti-semaglutide antibody titer | Count of participants | Up to 57 weeks | 
| Anti-semaglutide antibodies with in vitro neutralising effect to semaglutide | Count of participants | Week 0 to week 57 | 
| Anti-semaglutide antibodies cross reacting with endogenous GLP-1 | Count of participants | Week 0 to week 57 | 
| Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1 | Count of participants | Week 0 to week 57 | 
| Height velocity | cm/year | At week 26 | 
| Height velocity | cm/year | At week 52 | 
| Change from baseline in height SDS | SDS | Week 0, week 26 | 
| Change from baseline in bone age assessment, X-ray | Years | Week 0, week 52 | 
| Change from baseline in pubertal assessment (Tanner staging) | Stage 1-5 where 5 is full sexual maturity | Week 0, week 26 | 
| Change from baseline in pubertal assessment (Tanner staging) | Stage 1-5 where 5 is full sexual maturity | Week 0, week 52 | 
| Change from baseline in pulse rate | Beats/minute | Week 0, week 26 | 
| Change from baseline in pulse rate | Beats/minute | Week 0, week 52 | 
| Change from pre-dose to post-dose (25 and 40 min) in lactate | mmol/L | At week 12 | 
| Change from pre-dose to post-dose (25 and 40 min) in lactate | mmol/L | At week 26 | 
| Apparent clearance (CL/F) | L/h | Week 0 - week 52 | 
| Average concentration (Cavg) | nmol/L | Week 0 - week 52 | 
| SNAC plasma concentrations | ng/mL | Week 0 - week 52 |