Clinical trial NCT02527200: Effect of Liraglutide for Weight Management in Paediatric Subjects With Prader-Willi Syndrome
Official title: Effect of Liraglutide for Weight Management in Paediatric Subjects With Prader-Willi Syndrome.
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: 2015-08-18
Enrollment: 56
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
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 paediatric subjects with Prader-Willi Syndrome.


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
* Confirmed diagnosis of PWS (Prader-Willi Syndrome) (by genetic testing)
* Male or female, age at the time of signing informed consent: - Part A: above or equal to 12 years and less than 18 years
* Tanner stage 2-5 pubertal development for part A, and Tanner stage 1 for part B
* BMI (body mass index) corresponding to equal or above 30 kg/m\^2 for adults by international cut-off points1 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 ( below 10 kg self-reported weight change)
* Testing has been performed to evaluate for adrenal insufficiency and documented in medical record

Exclusion Criteria:

* Type 1 diabetes mellitus (T1DM)
* Type 2 diabetes mellitus (T2DM)
* Calcitonin equal or above 50 ng/L
* No change in treatment plan with growth hormone (GH) from randomisation to the end of the open-label period patients on growth hormone to stay on, patients off GH to stay off during this period. Adjustments in doses of growth hormone will be permitted)
* Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroids Carcinoma (MTC)
* History of pancreatitis (acute or chronic)
* Treatment with any medication prescribed for weight loss within 90 days before screening (e.g. orlistat, zonisamide, topiramate/phentermine, lorcaserin, phentermine, bupropion/naltrexone,liraglutide, metformin)
* Untreated adrenal insufficiency
* Suggestive history of, or significant risk of gastroparesis (e.g. marked abdominal bloating post meal, history of vomiting, severe constipation), as judged by the Investigator

Primary outcomes:
measure: Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 16 Weeks
timeFrame: Week 0, Week 16
measure: Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 52 Weeks
timeFrame: Week 0, Week 52
Secondary outcomes:
measure: Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 16
timeFrame: At week 16
measure: Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 52
timeFrame: At week 52
measure: Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 16
timeFrame: At week 16
measure: Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 52
timeFrame: At week 52
measure: Percentage of Participants With no Increase in BMI SDS at Week 16
timeFrame: At week 16
measure: Percentage of Participants With no Increase in BMI SDS at Week 52
timeFrame: At week 52
measure: Change in BMI From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in BMI From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Body Weight (Kilogram (kg)) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Body Weight (kg) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Body Weight (Pounds (lb)) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Body Weight (lb) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Body Weight (Percentage [%]) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Body Weight (%) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Waist Circumference From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Waist Circumference From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Waist-to-hip Circumference Ratio From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Waist-to-hip Circumference Ratio From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Total Cholesterol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Total Cholesterol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Triglycerides From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Triglycerides From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Systolic and Diastolic Blood Pressure From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Systolic and Diastolic Blood Pressure From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Glycosylated Haemoglobin (HbA1c) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in HbA1c From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Fasting Plasma Glucose (FPG) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in FPG From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Fasting Insulin From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Fasting Insulin From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Fasting C Peptide From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Fasting C Peptide From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Number of Participants in Glycaemic Category at Week 16
timeFrame: week 16
measure: Number of Participants in Glycaemic Category at Week 52
timeFrame: Week 52
measure: Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Number of Treatment Emergent Adverse Events
timeFrame: From week 0 to week 54
measure: Number of Severe Treatment Emergent Episodes of Hypoglycaemia
timeFrame: From week 0 to week 54
measure: Number of Blood Glucose Confirmed Symptomatic Episodes of Hypoglycaemia
timeFrame: From week 0 to week 54
measure: Number of Participants With Occurrence of Anti-liraglutide Antibodies
timeFrame: From week 0 to week 54
measure: Number of Participants With Change in Electrocardiogram (ECG) From Baseline at Week 16
timeFrame: Week 0, Week 16
measure: Number of Participants With Change in ECG From Baseline at Week 52
timeFrame: Week 0, Week 52
measure: Change in Pulse From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Pulse From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Haematology: Haemoglobin From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Haematology: Haemoglobin From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Haematology: Haematocrit From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Haematology: Haematocrit From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Haematology: Erythrocytes From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Haematology: Erythrocytes From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Biochemistry: Albumin From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Biochemistry: Albumin From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Calcitonin From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Calcitonin From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Estradiol (Females) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Estradiol (Females) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Change in Hormone Level: Testosterone (Males) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Change in Hormone Level: Testosterone (Males) From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Number of Participants With Change in Pubertal Status From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Number of Participants With Change in Pubertal Status From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Number of Participants With Change in Physical Examination From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Number of Participants With Change in Physical Examination From Baseline at Week 52
timeFrame: Week 0, week 52
measure: Height Velocity at Week 16
timeFrame: Week 16
measure: Height Velocity at Week 52
timeFrame: week 52
measure: Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 16
timeFrame: Week 0, week 16
measure: Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 52
timeFrame: Week 0, week 52
measure: Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 16
timeFrame: Week 0, week 16
measure: Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 52
timeFrame: Week 0, week 52
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Buffalo
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Mineola
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Camperdown
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: Parkville
country: Australia
facility: Novo Nordisk Investigational Site
state: Victoria
city: Calgary
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: ANGERS cedex 09
country: France
facility: Novo Nordisk Investigational Site
city: Bordeaux
country: France
facility: Novo Nordisk Investigational Site
city: Brest
country: France
facility: Novo Nordisk Investigational Site
city: BRON cedex
country: France
facility: Novo Nordisk Investigational Site
city: Haguenau
country: France
facility: Novo Nordisk Investigational Site
city: Lille
country: France
facility: Novo Nordisk Investigational Site
city: MARSEILLE Cédex 05
country: France
facility: Novo Nordisk Investigational Site
city: MONTPELLIER cedex 05
country: France
facility: Novo Nordisk Investigational Site
city: Nice
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Rouen
country: France
facility: Novo Nordisk Investigational Site
city: Toulouse cedex 9
country: France
facility: Novo Nordisk Investigational Site
city: Fiumicino
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Padova
country: Italy
facility: Novo Nordisk Investigational Site
city: Rotterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Grafton
country: New Zealand
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Samsun
country: Turkey
facility: Novo Nordisk Investigational Site
city: Trabzon
country: Turkey
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Diene G, Angulo M, Hale PM, Jepsen CH, Hofman PL, Hokken-Koelega A, Ramesh C, Turan S, Tauber M. Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity. J Clin Endocrinol Metab. 2022 Dec 17;108(1):4-12. doi: 10.1210/clinem/dgac549.