Clinical trial NCT04596631: A Research Study to Compare a New Medicine Oral Semaglutide to a Dummy Medicine in Children and Teenagers With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 132
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in glycosylated haemoglobin (HbA1c)
timeFrame: Week 0, week 26
Secondary outcomes:
measure: Change from baseline in fasting plasma glucose (FPG)
timeFrame: Week 0, week 26
measure: Change from baseline in body mass index (BMI) standard deviation score (SDS)
timeFrame: Week 0, week 26
measure: Change from baseline in glycosylated haemoglobin (HbA1c)
timeFrame: Week 0, week 52
measure: Change from baseline in FPG
timeFrame: Week 0, week 52
measure: Change from baseline in body weight
timeFrame: Week 0, week 26
measure: Change from baseline in body weight
timeFrame: Week 0, week 52
measure: Relative change from baseline in body weight
timeFrame: Week 0, week 26
measure: Relative change from baseline in body weight
timeFrame: Week 0, week 52
measure: Change from baseline in waist circumference
timeFrame: Week 0, week 26
measure: Change from baseline in waist circumference
timeFrame: Week 0, week 52
measure: Change from baseline in BMI SDS
timeFrame: Week 0, week 52
measure: BMI percentile (age and gender adjusted)
timeFrame: Week 0, week 26
measure: BMI percentile (age and gender adjusted)
timeFrame: Week 0, week 52
measure: Change from baseline in systolic blood pressure
timeFrame: Week 0, week 26
measure: Change from baseline in systolic blood pressure
timeFrame: Week 0, week 52
measure: Change from baseline in diastolic blood pressure
timeFrame: Week 0, week 26
measure: Change from baseline in diastolic blood pressure
timeFrame: Week 0, week 52
measure: 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
timeFrame: At week 26
measure: HbA1c equal to or below 6.5% (48 mmol/mol) (yes/no), American Association of Clinical Endocrinologists (AACE) target
timeFrame: At week 26
measure: HbA1c below 7.0% (53 mmol/mol) (yes/no), ADA target and ISPAD guidelines from 2018
timeFrame: At week 52
measure: HbA1c equal to or below 6.5% (48 mmol/mol) (yes/no), AACE targetat week 26
timeFrame: At week 52
measure: Time to additional anti-diabetic medication (to support the treatment policy estimand)
timeFrame: Week 0 - week 52
measure: Time to rescue medication (to support the hypothetical estimand)
timeFrame: Week 0 - week 52
measure: Number of treatment-emergent adverse events (TEAEs) during exposure to trial product
timeFrame: Week 0 - week 57
measure: Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes
timeFrame: From randomisation (week 0) to week 26
measure: Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes during exposure to trial product
timeFrame: Week 0 - week 57
measure: Treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode
timeFrame: From randomisation (week 0) to week 26
measure: Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode during exposure to trial product
timeFrame: Week 0 - week 57
measure: Change from baseline in amylase
timeFrame: Week 0, week 26
measure: Change from baseline in amylase
timeFrame: Week 0, week 52
measure: Change from baseline in lipase
timeFrame: Week 0, week 26
measure: Change from baseline in lipase
timeFrame: Week 0, week 52
measure: Change from baseline in insulin-like growth factor 1 (IGF-1)
timeFrame: Week 0, week 26
measure: Change from baseline in insulin-like growth factor 1 (IGF-1)
timeFrame: Week 0, week 52
measure: Change from baseline in insulin-like growth factor binding protein 3 (IGFBP 3)
timeFrame: Week 0, week 26
measure: Change from baseline in insulin-like growth factor binding protein 3 (IGFBP 3)
timeFrame: Week 0, week 52
measure: Change from baseline in calcitonin
timeFrame: Week 0, week 26
measure: Change from baseline in calcitonin
timeFrame: Week 0, week 52
measure: Change from baseline in estradiol (for girls)
timeFrame: Week 0, week 26
measure: Change from baseline in estradiol (for girls)
timeFrame: Week 0, week 52
measure: Change from baseline in testosterone (for boys)
timeFrame: Week 0, week 26
measure: Change from baseline in testosterone (for boys)
timeFrame: Week 0, week 52
measure: Change from baseline in prolactin
timeFrame: Week 0, week 26
measure: Change from baseline in prolactin
timeFrame: Week 0, week 52
measure: Change from baseline in thyroid stimulating hormone (TSH/thyrotropin)
timeFrame: Week 0, week 26
measure: Change from baseline in thyroid stimulating hormone (TSH/thyrotropin)
timeFrame: Week 0, week 52
measure: Change from baseline in follicle stimulating hormone (FSH)
timeFrame: Week 0, week 26
measure: Change from baseline in follicle stimulating hormone (FSH)
timeFrame: Week 0, week 52
measure: Change from baseline in luteinizing hormone (LH)
timeFrame: Week 0, week 26
measure: Change from baseline in luteinizing hormone (LH)
timeFrame: Week 0, week 52
measure: Change from baseline in dehydroepiandrosterone sulfate (DHEAS)
timeFrame: Week 0, week 26
measure: Change from baseline in dehydroepiandrosterone sulfate (DHEAS)
timeFrame: Week 0, week 52
measure: Anti-semaglutide antibody status
timeFrame: Week 0 - week 57
measure: Anti-semaglutide antibody titer
timeFrame: Up to 57 weeks
measure: Anti-semaglutide antibodies with in vitro neutralising effect to semaglutide
timeFrame: Week 0 to week 57
measure: Anti-semaglutide antibodies cross reacting with endogenous GLP-1
timeFrame: Week 0 to week 57
measure: Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1
timeFrame: Week 0 to week 57
measure: Height velocity
timeFrame: At week 26
measure: Height velocity
timeFrame: At week 52
measure: Change from baseline in height SDS
timeFrame: Week 0, week 26
measure: Change from baseline in bone age assessment, X-ray
timeFrame: Week 0, week 52
measure: Change from baseline in pubertal assessment (Tanner staging)
timeFrame: Week 0, week 26
measure: Change from baseline in pubertal assessment (Tanner staging)
timeFrame: Week 0, week 52
measure: Change from baseline in pulse rate
timeFrame: Week 0, week 26
measure: Change from baseline in pulse rate
timeFrame: Week 0, week 52
measure: Change from pre-dose to post-dose (25 and 40 min) in lactate
timeFrame: At week 12
measure: Change from pre-dose to post-dose (25 and 40 min) in lactate
timeFrame: At week 26
measure: Apparent clearance (CL/F)
timeFrame: Week 0 - week 52
measure: Average concentration (Cavg)
timeFrame: Week 0 - week 52
measure: SNAC plasma concentrations
timeFrame: Week 0 - week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Jacksonville
country: United States
facility: Nemours Chld Clnc Jacksonville
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Health
state: Florida
city: Tampa
country: United States
facility: University of South Florida Diabetes Center
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Uni School of Med-Ped
state: Indiana
city: Louisville
country: United States
facility: University Of Louisville Research Foundation
state: Kentucky
city: Baltimore
country: United States
facility: Barry J. Reiner, MD LLC
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Buffalo
country: United States
facility: UBMD Peds-Div of Endo/Diabetes
state: New York
city: Pittsburgh
country: United States
facility: UPMC Child Hosp-Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University HSC
state: Texas
city: San Antonio
country: United States
facility: Univ Of Texas Hlth Science Cntr
state: Texas
city: San Antonio
country: United States
facility: NE Clin Res of San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University_Richmond
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth Univ
state: Virginia
city: Westmead
country: Australia
facility: Westmead Children's Hospital- The Clinical Research Centre
state: New South Wales
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's' Hospital
state: Western Australia
city: Salzburg
country: Austria
facility: Universitätsklinik für Kinder und Jugendheilkunde Haus E
city: Ostrava-Poruba
country: Czechia
facility: Fakultní Nemocnice Ostrava
city: Athens
country: Greece
facility: University Hospital of Athens ATTIKON
state: Attica
city: Haidari-Athens
country: Greece
facility: University Hospital of Athens ATTIKON
state: Attica
city: Athens
country: Greece
facility: U.G.H. "Attikon", Pediatric Endocrinology Outpatient Clinic
city: Athens
country: Greece
facility: Henry Dunant Hospital Center,2nd Internal Medicine Clinic
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina, Endocrinology
city: Lamia
country: Greece
facility: General Hospital of Lamia
city: Larissa
country: Greece
facility: Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease
city: Thessaloniki
country: Greece
facility: "AHEPA" University General Hospital of Thessaloniki
city: Guntur
country: India
facility: Endolife Specialty Hospitals
state: Andhra Pradesh
city: Kolhapur
country: India
facility: Excel Endocrine Centre
state: Maharashtra
city: Mumbai
country: India
facility: P D Hinduja National Hospital and Medical Research Centre
state: Maharashtra
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Jaipur
country: India
facility: Eternal Heart Care Centre
state: Rajasthan
city: Hyderabad
country: India
facility: Ramdev Rao Hospital
state: Telangana
city: Hyderabad
country: India
facility: Dr P V Rao - Diabetes Research Centre
state: Telangana
city: Kolkata
country: India
facility: SSKM
state: West Bengal
city: Thriruvananthapuram
country: India
facility: Jothydev's Diabetes & Research Center
city: Beer Sheva
country: Israel
facility: Soroka Medical Center - Pediatric Endocrinology
city: Haifa
country: Israel
facility: Rambam Medical Center Children A Dept.
city: Hazmieh
country: Lebanon
facility: Chronic Care Center
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Wilayah Persekutuan Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Putrajaya
country: Malaysia
facility: Hospital Putrajaya
city: Puebla
country: Mexico
facility: Consultorio de Endocrinología y Pediatría
city: Rabat
country: Morocco
facility: Hôpital d'Enfants
city: Almere
country: Netherlands
facility: De Kinderkliniek
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Grafton
country: New Zealand
facility: Liggins Institute
city: Skopje
country: North Macedonia
facility: PHI University Clinic for Children's Diseases-Skopje
city: Lisboa
country: Portugal
facility: Hospital Da Luz S.A.
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Ponce
country: Puerto Rico
facility: Ponce Med School Found Inc
city: Brasov
country: Romania
facility: Diabet Center SRL
city: Bucharest
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii "M.S.Curie"
city: Constanta
country: Romania
facility: Emergency County Hospital Constanta
city: Omsk
country: Russian Federation
facility: GFHI Omsk Region "Regional Children's Clinical Hospital"
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital- Taipei
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou-Dept of Pediatrics
city: Dnipro
country: Ukraine
facility: CNPE "City Clinical Hospital #9 Dnipro City Council"
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Children Clincial Hospital_Lubyanka
city: Kyiv
country: Ukraine
facility: "Verum clinic" LLC
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: