Phase 3 N=56 Randomized Double-blind Treatment

Effect of Liraglutide for Weight Management in Paediatric Subjects With Prader-Willi Syndrome

Metabolism and Nutrition Disorder · Obesity

Bottom Line

View on ClinicalTrials.gov: NCT02527200 ↗

Enrolled (actual)

Serious AEs

7.1%

Results posted

Feb 2022

Primary outcome: Primary: Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 16 Weeks — -0.18; -0.18; -0.50; -0.48 SDS score

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: liraglutide (Drug); placebo (Drug)
Age: Pediatric, Adult · 6+ yrs
Sex: All
Sponsor: Novo Nordisk A/S
Primary completion: Nov 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 16 Weeks	-0.18; -0.18; -0.50; -0.48; -0.33; -0.29	—
PRIMARY Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 52 Weeks	-0.27; -0.13; -0.79; -0.71; -0.50; -0.36	—
SECONDARY Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 16	27.8; 8.3; 37.5; 57.1; 32.4; 26.3	—
SECONDARY Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 52	29.4; 18.2; 35.7; 42.9; 32.3; 27.8	—
SECONDARY Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 16	0; 0; 6.3; 14.3; 2.9; 5.3	—
SECONDARY Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 52	11.8; 0; 14.3; 28.6; 12.9; 11.1	—
SECONDARY Percentage of Participants With no Increase in BMI SDS at Week 16	66.7; 75.0; 87.5; 100; 76.5; 84.2	—
SECONDARY Percentage of Participants With no Increase in BMI SDS at Week 52	70.6; 72.7; 78.6; 100; 73.3; 81.3	—
SECONDARY Change in BMI From Baseline at Week 16	-0.9; -0.8; -1.1; -1.5; -1.0; -1.1	—
SECONDARY Change in BMI From Baseline at Week 52	0.8; -0.1; -0.6; -0.7; -0.7; -0.4	—
SECONDARY Change in Body Weight (Kilogram (kg)) From Baseline at Week 16	-1.7; -1.1; -0.6; -1.0; -1.2; -1.0	—
SECONDARY Change in Body Weight (kg) From Baseline at Week 52	-0.4; 1.9; 3.0; 2.8; 1.1; 2.3	—
SECONDARY Change in Body Weight (Pounds (lb)) From Baseline at Week 16	-3.7; -2.4; -1.4; -2.1; -2.6; -2.3	—
SECONDARY Change in Body Weight (lb) From Baseline at Week 52	-0.9; 4.3; 6.7; 6.2; 2.5; 5.0	—
SECONDARY Change in Body Weight (Percentage [%]) From Baseline at Week 16	-1.7; -0.7; -1.1; -2.2; -1.4; -1.2	—
SECONDARY Change in Body Weight (%) From Baseline at Week 52	-0.4; 2.3; 6.3; 4.9; 2.6; 3.3	—
SECONDARY Change in Waist Circumference From Baseline at Week 16	-2.50; -2.44; -0.73; -1.04; -1.70; -1.92	—
SECONDARY Change in Waist Circumference From Baseline at Week 52	-2.98; -3.48; 0.45; 0.97; -1.49; -2.09	—
SECONDARY Change in Waist-to-hip Circumference Ratio From Baseline at Week 16	-0.01; -0.02; 0.00; 0.01; -0.01; -0.01	—
SECONDARY Change in Waist-to-hip Circumference Ratio From Baseline at Week 52	-0.01; -0.04; -0.02; -0.01; -0.02; -0.03	—
SECONDARY Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 16	-0.8; -1.7; -1.2; -2.6; -1.0; -2.0	—
SECONDARY Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 52	-0.9; -0.6; -0.7; -2.6; -0.8; -1.3	—
SECONDARY Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 16	0.79; -0.57; -2.79; 1.87; -0.61; 0.24	—
SECONDARY Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 52	0.25; 0.14; -2.42; -0.37; -0.89; -0.03	—
SECONDARY Change in Total Cholesterol From Baseline at Week 16	0.99; 1.06; 1.02; 0.97; 1.00; 1.03	—
SECONDARY Change in Total Cholesterol From Baseline at Week 52	1.00; 1.06; 1.01; 1.07; 1.01; 1.06	—
SECONDARY Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 16	1.01; 1.13; 1.04; 0.96; 1.02; 1.07	—
SECONDARY Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 52	1.02; 1.12; 0.99; 1.06; 1.01; 1.10	—
SECONDARY Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 16	0.96; 1.00; 1.01; 1.12; 0.98; 1.04	—
SECONDARY Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 52	0.99; 1.02; 1.06; 1.08; 1.02; 1.04	—
SECONDARY Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 16	1.02; 1.09; 1.03; 0.93; 1.02; 1.04	—
SECONDARY Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 52	1.02; 1.07; 1.00; 1.07; 1.01; 1.07	—
SECONDARY Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 16	1.05; 0.98; 1.05; 0.80; 1.05; 0.93	—
SECONDARY Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 52	1.06; 0.95; 1.03; 1.13; 1.04; 1.01	—
SECONDARY Change in Triglycerides From Baseline at Week 16	1.04; 0.99; 1.05; 0.80; 1.05; 0.93	—
SECONDARY Change in Triglycerides From Baseline at Week 52	1.07; 0.94; 1.04; 1.12; 1.06; 1.00	—
SECONDARY Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 16	1.52; 1.31; 1.04; 0.99; 1.31; 1.21	—
SECONDARY Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 52	1.15; 1.45; 0.85; 1.05; 1.01; 1.32	—
SECONDARY Change in Systolic and Diastolic Blood Pressure From Baseline at Week 16	-5; -2; 2; 2; -1; -1	—
SECONDARY Change in Systolic and Diastolic Blood Pressure From Baseline at Week 52	-5; 4; 4; 7; -1; 5	—
SECONDARY Change in Glycosylated Haemoglobin (HbA1c) From Baseline at Week 16	-0.2; 0; -0.2; -0.2; -0.2; -0.1	—
SECONDARY Change in HbA1c From Baseline at Week 52	-0.2; 0.1; -0.2; -0.1; -0.2; 0.1	—
SECONDARY Change in Fasting Plasma Glucose (FPG) From Baseline at Week 16	-0.2; 0.1; -0.1; 0.2; -0.2; 0.1	—
SECONDARY Change in FPG From Baseline at Week 52	0; 0.3; 0; 0; 0; 0.2	—
SECONDARY Change in Fasting Insulin From Baseline at Week 16	1.59; 0.78; 1.43; 1.32; 1.52; 0.97	—
SECONDARY Change in Fasting Insulin From Baseline at Week 52	2.03; 0.79; 1.45; 1.22; 1.78; 0.96	—
SECONDARY Change in Fasting C Peptide From Baseline at Week 16	1.14; 0.86; 1.11; 1.08; 1.13; 0.94	—
SECONDARY Change in Fasting C Peptide From Baseline at Week 52	1.34; 0.91; 1.15; 1.09; 1.26; 0.98	—
SECONDARY Number of Participants in Glycaemic Category at Week 16	16; 8; 11; 5; 27; 13	—
SECONDARY Number of Participants in Glycaemic Category at Week 52	13; 4; 10; 2; 23; 6	—
SECONDARY Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 16	1.69; 0.70; 1.55; 1.07; 1.63; 0.82	—
SECONDARY Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 52	2.24; 0.65; 1.50; 1.25; 1.91; 0.88	—
SECONDARY Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 16	1.57; 0.80; 1.43; 1.33; 1.51; 0.97	—
SECONDARY Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 52	2.26; 0.88; 1.45; 1.24; 1.90; 1.02	—
SECONDARY Number of Treatment Emergent Adverse Events	134; 37; 159; 8; 293; 45	—
SECONDARY Number of Severe Treatment Emergent Episodes of Hypoglycaemia	0; 0; 1; 0; 1; 0	—
SECONDARY Number of Blood Glucose Confirmed Symptomatic Episodes of Hypoglycaemia	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Occurrence of Anti-liraglutide Antibodies	2; 1; 3; 14; 8; 22	—
SECONDARY Number of Participants With Change in Electrocardiogram (ECG) From Baseline at Week 16	20; 12; 17; 6; 37; 18	—
SECONDARY Number of Participants With Change in ECG From Baseline at Week 52	20; 12; 17; 6; 37; 18	—
SECONDARY Change in Pulse From Baseline at Week 16	2; -2; 1; -9; 2; -4	—
SECONDARY Change in Pulse From Baseline at Week 52	1; -8; 10; -6; 5; -7	—
SECONDARY Change in Haematology: Haemoglobin From Baseline at Week 16	-0.18; 0.06; -0.20; -0.07; -0.19; 0.01	—
SECONDARY Change in Haematology: Haemoglobin From Baseline at Week 52	-0.14; -0.01; -0.02; -0.02; -0.09; -0.01	—
SECONDARY Change in Haematology: Haematocrit From Baseline at Week 16	-1.8; -0.5; 0.4; -0.6; -0.9; -0.5	—
SECONDARY Change in Haematology: Haematocrit From Baseline at Week 52	-1.4; 0; -0.2; -0.8; -0.9; -0.3	—
SECONDARY Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 16	6; -21; 8; 19; 7; -8	—
SECONDARY Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 52	18; -7; -2; 37; 10; 5	—
SECONDARY Change in Haematology: Erythrocytes From Baseline at Week 16	-0.1; 0; 0.1; 0; -0.1; 0	—
SECONDARY Change in Haematology: Erythrocytes From Baseline at Week 52	-0.1; 0; -0.1; 0; -0.1; 0	—
SECONDARY Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 16	1; 0; 2; 0; 1; 0	—
SECONDARY Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 52	3; -4; 3; 5; 3; -1	—
SECONDARY Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 16	-3; 16; 3; -5; -1; 10	—
SECONDARY Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 52	30; -4; 25; -8; 28; -5	—
SECONDARY Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 16	0.03; -0.51; 0; 0.09; 0.02; -0.31	—
SECONDARY Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 52	-0.38; -0.34; -0.21; -0.04; -0.31; -0.24	—
SECONDARY Change in Biochemistry: Albumin From Baseline at Week 16	0; 0; 0; 0; 0; 0	—
SECONDARY Change in Biochemistry: Albumin From Baseline at Week 52	-0.1; -0.1; 0; 0; 0; -0.1	—
SECONDARY Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 16	-0.01; -0.17; 0.17; -0.04; 0.07; -0.12	—
SECONDARY Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 52	0.03; -0.14; -0.01; 0.17; 0.01; -0.01	—
SECONDARY Change in Hormone Level: Calcitonin From Baseline at Week 16	0; 0; 0.3; 0; 0.1; 0	—
SECONDARY Change in Hormone Level: Calcitonin From Baseline at Week 52	0.1; 0; 0.5; 0; 0.3; 0	—
SECONDARY Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 16	-0.34; -0.01; -0.09; -0.59; -0.23; -0.23	—
SECONDARY Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 52	0.02; -0.48; -0.75; -0.17; -0.30; -0.38	—
SECONDARY Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 16	-0.6; 0.3; 0.7; 0.1; -0.1; 0.2	—
SECONDARY Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 52	-0.4; 1.9; -0.1; 0.8; -0.3; 1.5	—
SECONDARY Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 16	-56.89; -28.23; 2.41; -14.23; -30.31; -23.86	—
SECONDARY Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 52	-25.90; -103.45; -1.47; 10.40; -15.04; -59.66	—
SECONDARY Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 16	0.16; 0.21; 0.25; 1.00; 0.20; 0.46	—
SECONDARY Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 52	0.77; 0.76; 0.25; 0.74; 0.55; 0.76	—
SECONDARY Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 16	-0.04; 0.06; -0.07; 0.22; -0.05; 0.12	—
SECONDARY Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 52	0.16; 0.06; 0.37; 0.30; 0.24; 0.14	—
SECONDARY Change in Hormone Level: Estradiol (Females) From Baseline at Week 16	0.9; 9.2; 1.6; 0; 1.2; 6.1	—
SECONDARY Change in Hormone Level: Estradiol (Females) From Baseline at Week 52	7.0; 13.7; 1.6; 0; 4.1; 11.0	—
SECONDARY Change in Hormone Level: Testosterone (Males) From Baseline at Week 16	1.55; 0.61	—
SECONDARY Change in Hormone Level: Testosterone (Males) From Baseline at Week 52	0.62; -0.34	—
SECONDARY Number of Participants With Change in Pubertal Status From Baseline at Week 16	0; 0; 11; 2; 11; 2	—
SECONDARY Number of Participants With Change in Pubertal Status From Baseline at Week 52	0; 0; 11; 2; 11; 2	—
SECONDARY Number of Participants With Change in Physical Examination From Baseline at Week 16	14; 10; 12; 5; 26; 15	—
SECONDARY Number of Participants With Change in Physical Examination From Baseline at Week 52	14; 10; 12; 5; 26; 15	—
SECONDARY Height Velocity at Week 16	2.113; 2.718; 4.190; 6.898; 3.090; 4.258	—
SECONDARY Height Velocity at Week 52	1.564; 1.839; 4.752; 5.620; 3.004; 3.173	—
SECONDARY Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 16	1; 3; 0; 0; 1; 1	—
SECONDARY Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 52	1; 3; 0; 0; 1; 0	—
SECONDARY Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 16	-2; 1	—
SECONDARY Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 52	-2; 0	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02527200). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.