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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Oral semaglutide; Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Not yet recruiting
      • Gosford Hospital
    • Westmead, New South Wales, Australia, 2145
      • Not yet recruiting
      • Westmead Children's Hospital- The Clinical Research Centre
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Not yet recruiting
      • Women's & Children's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Children's Hospital
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Murdoch Children'S Research Institute
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Perth Children's' Hospital
• Austria
  • Salzburg, Austria, 5020
    • Recruiting
    • Universitätsklinik für Kinder und Jugendheilkunde Haus E
• Belgium
  • Brussel, Belgium, 1090
    • Withdrawn
    • UZ Brussel
  • Bruxelles, Belgium, 1200
    • Withdrawn
    • Cliniques Universitaires Saint-Luc - Serv. Pédiatrie
  • Namur, Belgium, 5000
    • Withdrawn
    • CHU - UCL Namur - Site Sainte Elisabeth_Namur_1
• Czechia
  • Ostrava-Poruba, Czechia, 708 00
    • Recruiting
    • Fakultni Nemocnice Ostrava
  • Usti nad Labem, Czechia, 40011
    • Recruiting
    • Masarykova nemocnice v Usti nad Labem, o.z. - Detska klinika
• Greece
  • Athens, Greece, GR-11526
    • Recruiting
    • Henry Dunant Hospital Center,2nd Internal Medicine Clinic
  • Athens, Greece, GR-15125
    • Recruiting
    • Athens Paediatric Center
  • Athens, Greece, GR-15125
    • Recruiting
    • Iatriko Athinon (Athens Medical Canter)
  • Haidari-Athens, Greece, GR-12462
    • Recruiting
    • U.G.H. "Attikon", Pediatric Endocrinology Outpatient Clinic
  • Haidari-Athens, Greece, GR-12462
    • Recruiting
    • University Hospital of Athens ATTIKON
  • Ioannina, Greece, 45500
    • Recruiting
    • University General Hospital of Ioannina, Endocrinology
  • Lamia, Greece, GR35100
    • Recruiting
    • General Hospital of Lamia
  • Larissa, Greece, GR-41110
    • Recruiting
    • Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease
  • Penteli, Athens, Greece, 15236
    • Not yet recruiting
    • Pentelis Children's Hospital
  • Thessaloniki, Greece, GR-54636
    • Recruiting
    • "AHEPA" University General Hospital of Thessaloniki
  • Thessaloniki, Greece, GR-54643
    • Recruiting
    • EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes
• India
  • Thriruvananthapuram, India, 695 032
    • Recruiting
    • Jothydev's Diabetes & Research Center
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Recruiting
      • Endolife Specialty Hospitals
  • Maharashtra
    • Kolhapur, Maharashtra, India, 416008
      • Recruiting
      • Excel Endocrine Centre
    • Mumbai, Maharashtra, India, 4000016
      • Recruiting
      • P D Hinduja National Hospital and Medical Research Centre
  • New Delhi
    • New Dehli, New Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences
  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
      • Recruiting
      • Eternal Heart Care Centre
  • Telangana
    • Hyderabad, Telangana, India, 500072
      • Recruiting
      • Ramdev Rao Hospital
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • Withdrawn
      • SSKM
    • Kolkata, West Bengal, India, 700020
      • Not yet recruiting
      • SSKM
• Israel
  • Beer Sheva, Israel, 84101
    • Recruiting
    • Soroka Medical Center - Pediatric Endocrinology
  • Haifa, Israel, 31096
    • Recruiting
    • Rambam Medical Center Children A Dept.
• Lebanon
  • Hazmieh, Lebanon, 21211
    • Recruiting
    • Chronic Care Center
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
  • Putrajaya, Malaysia, 62250
    • Recruiting
    • Hospital Putrajaya
  • Wilayah Persekutuan Kuala Lumpur
    • Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia, 59100
      • Recruiting
      • University Malaya Medical Centre
• Mexico
  • Puebla, Mexico, 72190
    • Recruiting
    • Consultorio de Endocrinología y Pediatría
• Morocco
  • Rabat, Morocco, 10000
    • Recruiting
    • Hôpital D'Enfants
• Netherlands
  • Almere, Netherlands, 1315 RC
    • Suspended
    • De KinderKliniek
  • Den Bosch, Netherlands, 5223 GZ
    • Recruiting
    • Jeroen Bosch Ziekenhuis
• New Zealand
  • Grafton, New Zealand, 1023
    • Recruiting
    • Liggins Institute
• North Macedonia
  • Skopje, North Macedonia, 1000
    • Recruiting
    • PHI University Clinic for Children's Diseases-Skopje
• Portugal
  • Lisboa, Portugal, 1500-650
    • Recruiting
    • Hospital da Luz
  • Lisboa, Portugal, 1649-035
    • Active, not recruiting
    • Centro Hospitalar Lisboa Norte
  • Vila Nova de Gaia, Portugal, 4400-129
    • Recruiting
    • Centro Hospitalar de Vila Nova de Gaia
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Recruiting
    • Ponce Med School Found Inc
• Romania
  • Brasov, Romania, 500260
    • Recruiting
    • Diabet Center SRL
  • Bucharest, Romania, 041451
    • Recruiting
    • Spitalul Clinic de Urgenta pentru Copii "M.S.Curie"
  • Constanta, Romania, 900591
    • Recruiting
    • Emergency County Hospital Constanta
  • Dambovita
    • Targoviste, Dambovita, Romania, 130083
      • Recruiting
      • Spitalul Judetean de Urgenta Targoviste
• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
    • Withdrawn
    • SAHI Sverdlovsk Reg "Regional Children's Clinical Hospital"
  • Izhevsk, Russian Federation, 426009
    • Withdrawn
    • Republic Children's Hospital of Ministry of Health of Udmurt
  • Moscow, Russian Federation, 125373
    • Withdrawn
    • RMAPE
  • Novosibirsk, Russian Federation, 630048
    • Withdrawn
    • NSMU paediatric clinic
  • Omsk, Russian Federation, 644001
    • Completed
    • GFHI Omsk Region "Regional Children's Clinical Hospital"
  • Saint-Petersburg, Russian Federation, 191144
    • Withdrawn
    • SPSBHI City Children out-patient clinic #44
  • Tomsk, Russian Federation, 634050
    • Completed
    • Siberian State Medical University
• Taiwan
  • Taipei, Taiwan, 104
    • Recruiting
    • Mackay Memorial Hospital- Taipei
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Department of Pediatrics, Chang Gung Memorial Hospital-LinKo
• Ukraine
  • Dnipro, Ukraine, 49023
    • Recruiting
    • CNPE "City Clinical Hospital #9 Dnipro City Council"
  • Kharkiv, Ukraine, 61000
    • Recruiting
    • Kharkiv Regional Children Clincial Hospital_Lubyanka
  • Kiev, Ukraine, 01021
    • Withdrawn
    • Scientific and Practical Center of Endocrine Surgery
  • Kyiv, Ukraine, 03039
    • Completed
    • "Verum clinic" LLC
  • Kyiv, Ukraine, 04114
    • Withdrawn
    • Institute of Endocrinology and Metabolism of AMSU
  • Vinnytsia, Ukraine, 21010
    • Withdrawn
    • Vinnytsia Med University based on RegionalEndocrinDispensary
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Recruiting
    • Birmingham Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Withdrawn
      • UAB Ped Endo Children's Hosp
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hosp-Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Withdrawn
      • Yale School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Nemours Chld Clnc Jacksonville
    • Tampa, Florida, United States, 33612
      • Recruiting
      • University of South Florida Diabetes Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Recruiting
      • Columbus Research Foundation
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana Uni School of Med-Ped
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University Of Louisville Research Foundation
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Withdrawn
      • Pennington Biomed Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Recruiting
      • Barry J. Reiner, MD LLC
    • Baltimore, Maryland, United States, 21229
      • Withdrawn
      • Barry J. Reiner, MD LLC
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Suspended
      • University of Mississippi Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • UBMD Peds-Div of Endo/Diabetes
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Child Hosp-Pittsburgh
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Withdrawn
      • Monument Health Clinical Rsrch
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • Recruiting
      • Texas Tech University HSC
    • San Antonio, Texas, United States, 78207
      • Recruiting
      • Univ Of Texas Hlth Science Cntr
    • San Antonio, Texas, United States, 78233
      • Recruiting
      • NE Clin Res of San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University_Richmond

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide - max. tolerated dose; 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; Oral semaglutide treatment for 52 weeks. All participants will be dose-escalated to an individual maximum tolerated dose.
Placebo Comparator: Placebo (semaglutide); 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); Placebo treatment for 52 weeks.

What is the study measuring?

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 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
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
SNAC plasma concentrations	ng/mL	Week 0 - week 52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Estimated): February 17, 2025
• Study Completion (Estimated): March 17, 2026

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: NN9924-4437; U1111-1218-1527 (Other Identifier: World Health Organization (WHO)); 2018-002952-34 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No