Clinical trial NCT02918279: Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity
Official title: Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity. 56-week, Double-blind, Randomised, Parallel-group, Placebo-controlled Multi-national Trial Followed by a 26-week Period Off Study-drug
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolism and Nutrition Disorder
Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-09-28
Enrollment: 251
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted globally. The aim of this trial is to investigate the effect of liraglutide for weight management in pubertal adolescent subjects with obesity.


Eligibility criteria: Inclusion Criteria:

* Informed consent 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, age 12 to less than 18 years at the time of signing informed consent and less than 18 years at date of randomisation
* BMI corresponding to equal to or above 30 kg/m\^2 for adults by international cut-off points and equal or above the 95th percentile for age and sex (for diagnosis of obesity)
* Stable body weight during the previous 90 days before screening V2 (below 5 kg self-reported weight change)
* History of failing to lose sufficient weight with lifestyle modification as judged by the investigator and documented in subject's medical record

Exclusion Criteria:

* Pre-pubertal subjects (Tanner stage 1) at screening V2
* Type 1 diabetes mellitus (T1DM)
* Family or personal history of multiple endocrine neoplasia type 2 (MEN2)
* Medullary thyroid carcinoma (MTC)
* History of pancreatitis (acute or chronic)
* Subjects with secondary causes of obesity (i.e., hypothalamic, genetic or endocrine causes)
* Treatment with medications within 90 days before screening V2 that, based on the investigator's judgement, may cause significant weight change. This should also include treatment with any of the following medications: pramlintide, orlistat, zonisamide, topiramate, lorcaserin, phenteremine, bupropion, naltrexone, glucagon-like peptide-1 (GLP-1) receptor agonists, or metformin (used as treatment for obesity)
* Anti-diabetic treatment other than metformin
* History of major depressive disorder within 2 years before screening V2

Primary outcomes:
measure: Change in BMI SDS (Week 0, Week 56)
timeFrame: Week 0, week 56
Secondary outcomes:
measure: Percent of Subjects Achieving ≥5% Reduction in Baseline BMI
timeFrame: Weeks 30, 56 and 82
measure: Percent of Subjects Achieving ≥10% Reduction in Baseline BMI
timeFrame: Weeks 30, 56 and 82
measure: Change in BMI SDS ((Week 0, Week 30); (Week 0, Week 82); (Week 56, Week 82))
timeFrame: (Week 0, week 30); (Week 0, week 82); (Week 56, week 82)
measure: Change in BMI
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Body Weight (kg)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Body Weight (%)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Body Weight (lb)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Waist Circumference
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Waist-to-hip Circumference Ratio
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in hsCRP
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: Total Cholesterol (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: LDL-cholesterol (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: HDL-cholesterol (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: Non-HDL Cholesterol (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: VLDL Cholesterol (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: Triglycerides (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Lipid: FFA (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Systolic and Diastolic Blood Pressure
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in HbA1c
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in FPG
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting Insulin (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Fasting C-peptide (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Glycaemic Category
timeFrame: Week -2, week 30, week 56 and week 82
measure: Change in HOMA-B (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in HOMA-IR (Ratio to Baseline)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in IWQOL-Kids
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in BMI SDS (%)
timeFrame: (Week 0, week 30); (Week 0, week 56)
measure: Change in Nutritional Compliance
timeFrame: Week 0, week 30 and week 56
measure: Number of Treatment Emergent Adverse Events
timeFrame: Week 0-56 + 14 days
measure: Number of Treatment Emergent Hypoglycaemic Episodes (ADA/ISPAD Classification)
timeFrame: Week 0-56 + 14 days
measure: Number of Treatment Emergent Hypoglycaemic Episodes (Novo Nordisk/ISPAD Classification)
timeFrame: Week 0-56 + 14 days
measure: Occurrence of Anti-liraglutide Antibodies
timeFrame: Weeks 0, 30, 56, 58, 70 and 82
measure: Change in Pulse
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in ECG
timeFrame: Week -14, week 30, week 56 and week 82
measure: Change in Haematology: Haemoglobin
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Haematology: Haematocrit
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Haematology: Thrombocytes, Leucocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes and Monocytes
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Haematology: Erythrocytes
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Biochemistry: Creatinine and Bilirubin (Total)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Biochemistry: Urea (BUN), Sodium, Potassium, Calcium Total and Calcium Albumin-corrected
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Biochemistry: Albumin
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Biochemistry: CEA
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: Calcitonin
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: TSH and Prolactin
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: Free T4 and ACTH
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: IGF-1 and Cortisol
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: DHEAS
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: LH and FSH
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: Estradiol (Females)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Hormone Level: Testosterone (Males)
timeFrame: Week 0, week 30, week 56 and week 82
measure: Change in NTX1
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in CTX1
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in P1NP
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Alkaline Phosphatase (Bone)
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Pubertal Status
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in Physical Examination
timeFrame: Week 0, week 30, week 56 and week 82
measure: Change in Height SDS
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in C-SSRS
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
measure: Change in PHQ-9
timeFrame: (Week 0, week 30); (Week 0, week 56); (Week 56, week 82)
Other outcomes:
Locations:
city: Meridian
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Baton Rouge
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Buffalo
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Pittsburgh
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Goose Creek
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edegem
country: Belgium
facility: Novo Nordisk Investigational Site
city: Hasselt
country: Belgium
facility: Novo Nordisk Investigational Site
city: Leuven
country: Belgium
facility: Novo Nordisk Investigational Site
city: Namur
country: Belgium
facility: Novo Nordisk Investigational Site
city: Ciudad Madero
country: Mexico
facility: Novo Nordisk Investigational Site
state: Tamaulipas
city: Puebla
country: Mexico
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Rostov-on-Don
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Samara
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Stavropol
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tomsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Ufa
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Göteborg
country: Sweden
facility: Novo Nordisk Investigational Site
city: Huddinge
country: Sweden
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Uppsala
country: Sweden
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR)
role: STUDY_DIRECTOR
References:
citation: Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020 May 28;382(22):2117-2128. doi: 10.1056/NEJMoa1916038. Epub 2020 Mar 31.