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

Diabetes Mellitus, Type 2 Clinical Trial

— PIONEER TEENS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04596631
• Other study ID #: NN9924-4437
• Secondary ID: U1111-1218-15272
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2, 2020
• Est. completion date: March 17, 2026

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: March 17, 2026
• Est. primary completion date: February 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Oral semaglutide
Oral semaglutide treatment for 52 weeks. All participants will be dose-escalated to an individual maximum tolerated dose.
• Placebo (semaglutide)
Placebo treatment for 52 weeks.

Locations

Country	Name	City	State
Australia	Monash Children's Hospital	Clayton	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Perth Children's' Hospital	Nedlands	Western Australia
Australia	Women's & Children's Hospital	North Adelaide	South Australia
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	Westmead Children's Hospital- The Clinical Research Centre	Westmead	New South Wales
Austria	Universitätsklinik für Kinder und Jugendheilkunde Haus E	Salzburg
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires Saint-Luc - Serv. Pédiatrie	Bruxelles
Belgium	CHU - UCL Namur - Site Sainte Elisabeth_Namur_1	Namur
Czechia	Fakultní Nemocnice Ostrava	Ostrava-Poruba
Czechia	Fakultní Nemocnice Ostrava	Ostrava-Poruba
Czechia	Masarykova nemocnice v Usti nad Labem, o.z. - Detska klinika	Usti nad Labem
Greece	Athens Paediatric Center	Athens
Greece	Henry Dunant Hospital Center,2nd Internal Medicine Clinic	Athens
Greece	Iatriko Athinon (Athens Medical Canter)	Athens
Greece	U.G.H. "Attikon", Pediatric Endocrinology Outpatient Clinic	Haidari-Athens
Greece	University Hospital of Athens ATTIKON	Haidari-Athens	Attica
Greece	University General Hospital of Ioannina, Endocrinology	Ioannina
Greece	General Hospital of Lamia	Lamia
Greece	Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease	Larissa
Greece	Pentelis Children's Hospital	Penteli, Athens
Greece	"AHEPA" University General Hospital of Thessaloniki	Thessaloniki
Greece	EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes	Thessaloniki
India	Endolife Specialty Hospitals	Guntur	Andhra Pradesh
India	Ramdev Rao Hospital	Hyderabad	Telangana
India	Eternal Heart Care Centre	Jaipur	Rajasthan
India	Excel Endocrine Centre	Kolhapur	Maharashtra
India	SSKM	Kolkata	West Bengal
India	SSKM	Kolkata	West Bengal
India	P D Hinduja National Hospital and Medical Research Centre	Mumbai	Maharashtra
India	All India Institute of Medical Sciences	New Dehli	New Delhi
India	Jothydev's Diabetes & Research Center	Thriruvananthapuram
Israel	Soroka Medical Center - Pediatric Endocrinology	Beer Sheva
Israel	Rambam Medical Center Children A Dept.	Haifa
Lebanon	Chronic Care Center	Hazmieh
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Putrajaya	Putrajaya
Mexico	Consultorio de Endocrinología y Pediatría	Puebla
Morocco	Hôpital d'Enfants	Rabat
Netherlands	De Kinderkliniek	Almere
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
New Zealand	Liggins Institute	Grafton
North Macedonia	PHI University Clinic for Children's Diseases-Skopje	Skopje
Portugal	Centro Hospitalar Lisboa Norte	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Puerto Rico	Ponce Med School Found Inc	Ponce
Romania	Diabet Center SRL	Brasov
Romania	Spitalul Clinic de Urgenta pentru Copii "M.S.Curie"	Bucharest
Romania	Emergency County Hospital Constanta	Constanta
Romania	Spitalul Judetean de Urgenta Targoviste	Targoviste	Dambovita
Russian Federation	SAHI Sverdlovsk Reg "Regional Children's Clinical Hospital"	Ekaterinburg
Russian Federation	Republic Children's Hospital of Ministry of Health of Udmurt	Izhevsk
Russian Federation	RMAPE	Moscow
Russian Federation	NSMU paediatric clinic	Novosibirsk
Russian Federation	GFHI Omsk Region "Regional Children's Clinical Hospital"	Omsk
Russian Federation	SPSBHI City Children out-patient clinic #44	Saint-Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Taiwan	Mackay Memorial Hospital- Taipei	Taipei
Taiwan	Department of Pediatrics, Chang Gung Memorial Hospital-LinKo	Taoyuan
Ukraine	CNPE "City Clinical Hospital #9 Dnipro City Council"	Dnipro
Ukraine	Kharkiv Regional Children Clincial Hospital_Lubyanka	Kharkiv
Ukraine	Scientific and Practical Center of Endocrine Surgery	Kiev
Ukraine	"Verum clinic" LLC	Kyiv
Ukraine	Institute of Endocrinology and Metabolism of AMSU	Kyiv
Ukraine	Vinnytsia Med University based on RegionalEndocrinDispensary	Vinnytsia
United Kingdom	Birmingham Children's Hospital	Birmingham
United States	Texas Tech University HSC	Amarillo	Texas
United States	Children's Healthcare Atlanta	Atlanta	Georgia
United States	Barry J. Reiner, MD LLC	Baltimore	Maryland
United States	Barry J. Reiner, MD LLC	Baltimore	Maryland
United States	Pennington Biomed Research Center	Baton Rouge	Louisiana
United States	UAB Ped Endo Children's Hosp	Birmingham	Alabama
United States	UBMD Peds-Div of Endo/Diabetes	Buffalo	New York
United States	Pediatric Endo UVHS	Charlottesville	Virginia
United States	Columbus Research Foundation	Columbus	Georgia
United States	Indiana Uni School of Med-Ped	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Chld Clnc Jacksonville	Jacksonville	Florida
United States	Children's Hosp-Los Angeles	Los Angeles	California
United States	University Of Louisville Research Foundation	Louisville	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School Of Medicine	New Haven	Connecticut
United States	UPMC Child Hosp-Pittsburgh	Pittsburgh	Pennsylvania
United States	Monument Health Clinical Rsrch	Rapid City	South Dakota
United States	Virginia Commonwealth University_Richmond	Richmond	Virginia
United States	NE Clin Res of San Antonio	San Antonio	Texas
United States	Univ Of Texas Hlth Science Cntr	San Antonio	Texas
United States	University of South Florida Diabetes Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  Greece,  India,  Israel,  Lebanon,  Malaysia,  Mexico,  Morocco,  Netherlands,  New Zealand,  North Macedonia,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

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