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

• ClinicalTrials.gov Identifier: NCT02527200
• Recruitment Status: Completed
• First Posted: August 18, 2015
• Results First Posted: February 3, 2022
• Last Update Posted: November 21, 2022
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metabolism and Nutrition Disorder; Obesity	Drug: liraglutide; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Liraglutide for Weight Management in Paediatric Subjects With Prader-Willi Syndrome.
• Actual Study Start Date: November 9, 2015
• Actual Primary Completion Date: November 4, 2020
• Actual Study Completion Date: November 19, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Liraglutide	Drug: liraglutide; Injected s.c./ subcutaneously (under the skin) This trial consists of a part A and a part B. Part A of the trial is conducted in obese adolescents with PWS. Part B of the trial is conducted in obese children with PWS. Entry into part A and part B of the trial will be sequential.
Placebo Comparator: Placebo	Drug: placebo; Injected s.c./ subcutaneously (under the skin) This trial consists of a part A and a part B. Part A of the trial is conducted in obese adolescents with PWS. Part B of the trial is conducted in obese children with PWS. Entry into part A and part B of the trial will be sequential.

Outcome Measures

Primary Outcome Measures :

1. Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 16 Weeks [ Time Frame: Week 0, Week 16 ]
   Change in BMI SDS from baseline to week 16 is presented. BMI SDS also called Z-scores, was calculated using the following formula: Z=[(y / M)^L - 1] / S*L; where L, M and S are median (M), Box-cox power (L) and variation coefficient (S) of children/adolescents', y= individual BMI. BMI provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. Possible values range from -3 to +3, a negative score being beneficial.
2. Change in Body Mass Index (BMI) Standard Deviation Score (SDS) From Baseline to 52 Weeks [ Time Frame: Week 0, Week 52 ]
   Change in BMI SDS from baseline to week 52 is presented. BMI SDS also called Z-scores, was calculated using the following formula: Z=[(y / M)^L - 1] / S*L; where L, M and S are median (M), Box-cox power (L) and variation coefficient (S) of children/adolescents', y= individual BMI. BMI provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. Possible values range from -3 to +3, a negative score being beneficial.

Secondary Outcome Measures :

1. Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 16 [ Time Frame: At week 16 ]
   Percentage of participants achieving more than or equal to (≥) 5% reduction in their baseline (week 0) BMI at week 16 is presented. In below table, 'Yes' infers percentage of participants who achieved ≥ 5% reduction in their baseline (week 0) BMI at week 16 and 'No' infers percentage of participants who did not achieve ≥ 5% reduction in their baseline (week 0) BMI at week 16.
2. Percentage of Participants Achieving ≥ 5% Reduction in Baseline BMI at Week 52 [ Time Frame: At week 52 ]
   Percentage of participants achieving more than or equal to (≥) 5% reduction in their baseline (week 0) BMI at week 52 is presented. In below table, 'Yes' infers percentage of participants who achieved ≥ 5% reduction in their baseline (week 0) BMI at week 52 and 'No' infers percentage of participants who did not achieve ≥ 5% reduction in their baseline (week 0) BMI at week 52.
3. Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 16 [ Time Frame: At week 16 ]
   Percentage of participants achieving more than or equal to (≥) 10% reduction in their baseline (week 0) BMI at week 16 is presented. In below table, 'Yes' infers percentage of participants who achieved ≥ 10% reduction in their baseline (week 0) BMI at week 16 and 'No' infers percentage of participants who did not achieve ≥ 10% reduction in their baseline (week 0) BMI at week 16.
4. Percentage of Participants Achieving ≥ 10% Reduction in Baseline BMI at Week 52 [ Time Frame: At week 52 ]
   Percentage of participants achieving more than or equal to (≥) 10% reduction in their baseline (week 0) BMI at week 52 is presented. In below table, 'Yes' infers percentage of participants who achieved ≥ 10% reduction in their baseline (week 0) BMI at week 52 and 'No' infers percentage of participants who did not achieve ≥ 10% reduction in their baseline (week 0) BMI at week 52.
5. Percentage of Participants With no Increase in BMI SDS at Week 16 [ Time Frame: At week 16 ]
   Percentage of participants with no increase in BMI SDS at week 16 is presented. In below table, 'Yes' infers percentage of participants with no increase in BMI SDS at week 16 and 'No' infers percentage of participants with increase in BMI SDS at week 16.
6. Percentage of Participants With no Increase in BMI SDS at Week 52 [ Time Frame: At week 52 ]
   Percentage of participants with no increase in BMI SDS at week 52 is presented. In below table, 'Yes' infers percentage of participants with no increase in BMI SDS at week 52 and 'No' infers percentage of participants with increase in BMI SDS at week 52.
7. Change in BMI From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
   Change in body mass index (BMI) from baseline to week 16 is presented.
8. Change in BMI From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
   Change in body mass index (BMI) from baseline to week 52 is presented.
9. Change in Body Weight (Kilogram (kg)) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
   Change in body weight (kg) from baseline to week 16 is presented.
10. Change in Body Weight (kg) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in body weight (kg) from baseline to week 52 is presented.
11. Change in Body Weight (Pounds (lb)) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in body weight (lb) from baseline to week 16 is presented.
12. Change in Body Weight (lb) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in body weight (lb) from baseline to week 52 is presented.
13. Change in Body Weight (Percentage [%]) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in body weight (%) from baseline to week 16 is presented.
14. Change in Body Weight (%) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in body weight (%) from baseline to week 52 is presented.
15. Change in Waist Circumference From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in waist circumference from baseline to week 16 is presented.
16. Change in Waist Circumference From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in waist circumference from baseline to week 52 is presented.
17. Change in Waist-to-hip Circumference Ratio From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in waist-to-hip circumference ratio from baseline to week 16 is presented.
18. Change in Waist-to-hip Circumference Ratio From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in waist-to-hip circumference ratio from baseline to week 52 is presented.
19. Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in hyperphagia score (hyperphagia total score and hyperphagic behaviour, drive and severity score respectively), from baseline to week 16 is presented. The Hyperphagia Questionnaire (HQ)- Total Score. It contains 11 questions which are categorised into 3 subscales; Hyperphagic Behaviour, Hyperphagic Drive, and Hyperphagia Severity. The subscales are summed together to compute the Total Score. The Total Score ranges from 11-55, with higher scores indicating more hyperphagia and a worse outcome. The HQ-Behaviour Factor Score ranges from 5-25, with higher scores indicating more hyperphagic behaviours and a worse outcome. The HQ- Drive Factor Score ranges from 4-20, with higher scores indicating higher hyperphagic drive and a worse outcome. The HQ- Severity Factor Score ranges from 2-10, with higher scores indicating higher severity.
20. Change in Hyperphagia Score: Total Score and Hyperphagic Behaviour, Drive and Severity Score From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in hyperphagia score (hyperphagia total score and hyperphagic behaviour, drive and severity score respectively), from baseline to week 52 is presented.The Hyperphagia Questionnaire (HQ)- Total Score. It contains 11 questions which are categorised into 3 subscales; Hyperphagic Behaviour, Hyperphagic Drive, and Hyperphagia Severity. The subscales are summed together to compute the Total Score. The Total Score ranges from 11-55, with higher scores indicating more hyperphagia and a worse outcome. The HQ-Behaviour Factor Score ranges from 5-25, with higher scores indicating more hyperphagic behaviours and a worse outcome. The HQ- Drive Factor Score ranges from 4-20, with higher scores indicating higher hyperphagic drive and a worse outcome. The HQ- Severity Factor Score ranges from 2-10, with higher scores indicating higher severity.
21. Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in hsCRP from baseline to week 16 is presented.
22. Change in High Sensitivity C Reactive Protein (hsCRP) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in hsCRP from baseline to week 52 is presented.
23. Change in Total Cholesterol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in Total cholesterol (measured as millimoles per liter (mmol/L) from baseline to week 16 is presented as ratio to baseline.
24. Change in Total Cholesterol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in total cholesterol (measured as millimoles per liter (mmol/L) from baseline to week 52 is presented as ratio to baseline.
25. Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in LDL-cholesterol (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
26. Change in Low Density Lipoprotein (LDL)-Cholesterol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in LDL-cholesterol (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
27. Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in HDL-cholesterol (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
28. Change in High Density Lipoprotein (HDL)-Cholesterol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in HDL-cholesterol (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
29. Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in non-HDL cholesterol (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
30. Change in Non-high Density Lipoprotein (Non-HDL) Cholesterol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in non-HDL cholesterol (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
31. Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in VLDL cholesterol (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
32. Change in Very Low-density Lipoprotein (VLDL) Cholesterol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in VLDL cholesterol (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
33. Change in Triglycerides From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in triglycerides (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
34. Change in Triglycerides From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in triglycerides (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
35. Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in free fatty acids (measured as mmol/L) from baseline to week 16 is presented as ratio to baseline.
36. Change in Fasting Lipid: Free Fatty Acids (FFA) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in free fatty acids (measured as mmol/L) from baseline to week 52 is presented as ratio to baseline.
37. Change in Systolic and Diastolic Blood Pressure From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to week 16 is presented.
38. Change in Systolic and Diastolic Blood Pressure From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to week 52 is presented.
39. Change in Glycosylated Haemoglobin (HbA1c) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in HbA1c from baseline to week 16 is presented.
40. Change in HbA1c From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in HbA1c from baseline to week 52 is presented.
41. Change in Fasting Plasma Glucose (FPG) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in FPG from baseline to week 16 is presented.
42. Change in FPG From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in FPG from baseline to week 52 is presented.
43. Change in Fasting Insulin From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in fasting insulin (measured as picomoles per litre (pmol/L)) from baseline to week 16 is presented as ratio to baseline.
44. Change in Fasting Insulin From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in fasting insulin (measured as picomoles per litre (pmol/L)) from baseline to week 52 is presented as ratio to baseline.
45. Change in Fasting C Peptide From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in fasting C peptide (measured as nano moles per liter (nmol/L)) from baseline to week 16 is presented as ratio to baseline.
46. Change in Fasting C Peptide From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in fasting C peptide (measured as nano moles per liter (nmol/L)) from baseline to week 52 is presented as ratio to baseline.
47. Number of Participants in Glycaemic Category at Week 16 [ Time Frame: week 16 ]
    Number of participants in glycaemic categories, "normoglycaemia, pre-diabetes and type 2 diabetes" at Week 16 are presented. These categories were set as per the following criteria: 1) Normoglycaemia: FPG <5.6 mmol/L (<100 mg/dL) and/or HbA1c <5.7%. 2) Pre-diabetes: FPG 5.6-6.9 mmol/L (both inclusive), FPG 100-125 mg/dL (both inclusive) or HbA1c 5.7-6.4% (both inclusive). 3) Type 2 diabetes: FPG ≥7.0 mmol/L (≥126 mg/dL) and/or HbA1c ≥6.5%.
48. Number of Participants in Glycaemic Category at Week 52 [ Time Frame: Week 52 ]
    Number of participants in glycaemic categories, "normoglycaemia, pre-diabetes and type 2 diabetes" at Week 52 are presented. These categories were set as per the following criteria: 1) Normoglycaemia: FPG <5.6 mmol/L (<100 mg/dL) and/or HbA1c <5.7%. 2) Pre-diabetes: FPG 5.6-6.9 mmol/L (both inclusive), FPG 100-125 mg/dL (both inclusive) or HbA1c 5.7-6.4% (both inclusive). 3) Type 2 diabetes: FPG ≥7.0 mmol/L (≥126 mg/dL) and/or HbA1c ≥6.5%.
49. Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in HOMA-B from baseline to week 16 is presented as ratio to baseline. HOMA-B was calculated as: Beta-cell function (%) = 20·fasting insulin[mU/L]/(FPG[mmol/L]-3.5).
50. Change in Homeostasis Model Assessment of Beta-cell Function (HOMA-B) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in HOMA-B from baseline to week 52 is presented as ratio to baseline. HOMA-B was calculated as: Beta-cell function (%) = 20·fasting insulin[mU/L]/(FPG[mmol/L]-3.5).
51. Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in HOMA-IR from baseline to week 16 is presented as ratio to baseline. HOMA-IR was calculated as: Insulin resistance (%) = fasting plasma glucose [mmol/L] x fasting insulin [mmol/L]/ 22.5.
52. Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in HOMA-IR from baseline to week 52 is presented as ratio to baseline. HOMA-IR was calculated as: Insulin resistance (%) = fasting plasma glucose [mmol/L] x fasting insulin [mmol/L]/ 22.5.
53. Number of Treatment Emergent Adverse Events [ Time Frame: From week 0 to week 54 ]
    An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The endpoint was evaluated based on the data from on-treatment period. On-treatment period included AEs are with an onset date on or after the first day of trial product administration and any of the following dates, whichever came first: a) 14 days after the last day on trial product, or b) Follow-up visit (week 54) for participants with trial product discontinuation, or c) Last study visit (participants withdrawn without follow-up visit (week 54)).
54. Number of Severe Treatment Emergent Episodes of Hypoglycaemia [ Time Frame: From week 0 to week 54 ]
    Hypoglycaemic episode (blood glucose less than or equal to (<=) 3.9 mmol/L (70 mg/dL) Or greater than (>) 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 14 days after the last day on randomised treatment. Severe hypoglycaemia defined by American Diabetes Association (ADA) 2013 and International Society for Paediatric and Adolescent Diabetes (ISPAD) 2018: hypoglycaemic episode associated with severe cognitive impairment requiring external assistance for recovery. Endpoint was evaluated based on data from in-trial period which was defined as events with onset date on or after the first day of trial product administration and no later than the last study visit (week 54).
55. Number of Blood Glucose Confirmed Symptomatic Episodes of Hypoglycaemia [ Time Frame: From week 0 to week 54 ]
    Symptomatic blood glucose confirmed hypoglycaemia: An episode that is blood glucose confirmed by plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episode is defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 14 days after the last day on randomised treatment. Endpoint was evaluated based on data from in-trial period which was defined as events with onset date on or after the first day of trial product administration and no later than the last study visit (week 54).
56. Number of Participants With Occurrence of Anti-liraglutide Antibodies [ Time Frame: From week 0 to week 54 ]
    Number of participants with occurrence of anti-liraglutide antibodies is presented. In the below table, 'Yes' infers number of participants with occurrence of anti- liraglutide antibodies and 'No' infers number of participants without anti- liraglutide antibodies.
57. Number of Participants With Change in Electrocardiogram (ECG) From Baseline at Week 16 [ Time Frame: Week 0, Week 16 ]
    A 12-lead ECG was performed at baseline (week 0) and week 16 and categorised as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). Number of participants in each ECG category at week 0 and weeks 16 are presented.
58. Number of Participants With Change in ECG From Baseline at Week 52 [ Time Frame: Week 0, Week 52 ]
    A 12-lead ECG was performed at baseline (week 0) and week 52 and categorised as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). Number of participants in each ECG category at week 0 and week 52 are presented.
59. Change in Pulse From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in pulse from baseline to week 16 is presented.
60. Change in Pulse From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in pulse from baseline to week 52 is presented.
61. Change in Haematology: Haemoglobin From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in haemoglobin from baseline to week 16 is presented.
62. Change in Haematology: Haemoglobin From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in haemoglobin from baseline to week 52 is presented.
63. Change in Haematology: Haematocrit From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in haematocrit from baseline to week 16 is presented.
64. Change in Haematology: Haematocrit From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in haematocrit from baseline to week 52 is presented.
65. Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in thrombocytes, leukocytes, eosinophils, neutrophils, basophils, lymphocytes, monocytes from baseline to week 16 is presented.
66. Change in Haematology: Thrombocytes, Leukocytes, Eosinophils, Neutrophils, Basophils, Lymphocytes, Monocytes From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in thrombocytes, leukocytes, eosinophils, neutrophils, basophils, lymphocytes, monocytes from baseline to week 52 is presented.
67. Change in Haematology: Erythrocytes From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in erythrocytes from baseline to week 16 is presented.
68. Change in Haematology: Erythrocytes From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in erythrocytes from baseline to week 52 is presented.
69. Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in creatinine and bilirubin (total) from baseline to week 16 is presented.
70. Change in Biochemistry: Creatinine and Bilirubin (Total) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in creatinine and bilirubin (total) from baseline to week 52 is presented.
71. Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in creatine kinase, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) from baseline to week 16 is presented.
72. Change in Biochemistry: Creatine Kinase, Amylase, Lipase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in creatine kinase, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) from baseline to week 52 is presented.
73. Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in urea, sodium, potassium, calcium total and calcium albumin-corrected from baseline to week 16 is presented.
74. Change in Biochemistry: Urea, Sodium, Potassium, Calcium Total and Calcium Albumin-corrected From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in urea, sodium, potassium, calcium total and calcium albumin-corrected from baseline to week 52 is presented.
75. Change in Biochemistry: Albumin From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in albumin from baseline to week 16 is presented.
76. Change in Biochemistry: Albumin From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in albumin from baseline to week 52 is presented.
77. Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in CEA serum from baseline to week 16 is presented.
78. Change in Hormone Level: Carcinoembryonic Antigen (CEA) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in CEA serum from baseline to week 52 is presented.
79. Change in Hormone Level: Calcitonin From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in calcitonin from baseline to week 16 is presented.
80. Change in Hormone Level: Calcitonin From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in calcitonin from baseline to week 52 is presented.
81. Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in TSH and prolactin from baseline to week 16 is presented.
82. Change in Hormone Level: Thyroid Stimulating Hormone (TSH) and Prolactin From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in TSH and prolactin from baseline to week 52 is presented.
83. Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in free T4 and ACTH from baseline to week 16 is presented.
84. Change in Hormone Level: Free Thyroxine (Free T4) and Adrenocorticotropic Hormone (ACTH) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in free T4 and ACTH from baseline to week 52 is presented.
85. Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in IGF-1 and cortisol from baseline to week 16 is presented.
86. Change in Hormone Level: Insulin-like Growth Factor-1 (IGF-1) and Cortisol From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in IGF-1 and cortisol from baseline to week 52 is presented.
87. Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in DHEAS from baseline to week 16 is presented.
88. Change in Hormone Level: Dehydroepiandrosterone Sulfate (DHEAS) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in DHEAS from baseline to week 52 is presented.
89. Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in LH and FSH from baseline to week 16 is presented.
90. Change in Hormone Level: Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in LH and FSH from baseline to week 52 is presented.
91. Change in Hormone Level: Estradiol (Females) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in estradiol (only for females) from baseline to week 16 is presented.
92. Change in Hormone Level: Estradiol (Females) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in estradiol (only for females) from baseline to week 52 is presented.
93. Change in Hormone Level: Testosterone (Males) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    Change in testosterone (only for males) from baseline to week 16 is presented. The testosterone analysis for Part B could not be performed due to an unforeseen change in the assay used by the central laboratory to measure testosterone during the trial. This change in methodology prevented a direct comparison of values measured at different time points during the trial.
94. Change in Hormone Level: Testosterone (Males) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    Change in testosterone (only for males) from baseline to week 52 is presented. The testosterone analysis for Part B could not be performed due to an unforeseen change in the assay used by the central laboratory to measure testosterone during the trial. This change in methodology prevented a direct comparison of values measured at different time points during the trial.
95. Number of Participants With Change in Pubertal Status From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    This outcome measure presents "pubertal status results" which is based on Tanner staging recorded at baseline (week 0), week 16. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Results are presented for the following categories: 1) For female: breast development and pubic hair development, 2) For male: penis development and pubic hair development. Each category shows number of participants in stages 1 to 5, where stage 1 represents "early pubertal development" and stage 5 represents "pubertal development equivalent to that of an adult".
96. Number of Participants With Change in Pubertal Status From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    This outcome measure presents "pubertal status results" which is based on Tanner staging recorded at baseline (week 0) and week 52. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Results are presented for the following categories: 1) For female: breast development and pubic hair development, 2) For male: penis development and pubic hair development. Each category shows number of participants in stages 1 to 5, where stage 1 represents "early pubertal development" and stage 5 represents "pubertal development equivalent to that of an adult".
97. Number of Participants With Change in Physical Examination From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
    This outcome measure presents number of participants with physical examination findings, "normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS)" at baseline (week 0), week 16. These findings were categorised by the investigator. Results include examination of: general appearance; head, ears, eyes, nose, throat, neck; respiratory system; cardiovascular system (CVS); gastrointestinal (GI) system including mouth; musculoskeletal system; central nervous system (CNS) and peripheral nervous system (PNS); skin; thyroid gland and lymph node palpation.
98. Number of Participants With Change in Physical Examination From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
    This outcome measure presents number of participants with physical examination findings, "normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS)" at baseline (week 0) and week 52. These findings were categorised by the investigator. Results include examination of: general appearance; head, ears, eyes, nose, throat, neck; respiratory system; cardiovascular system (CVS); gastrointestinal (GI) system including mouth; musculoskeletal system; central nervous system (CNS) and peripheral nervous system (PNS); skin; thyroid gland and lymph node palpation.
99. Height Velocity at Week 16 [ Time Frame: Week 16 ]
    Height velocity was the change in height per year. The height velocity was calculated as the difference between current height and baseline divided by by time duration in days between those measurement time points and multiplied by 365 days. Height velocity calculated at Weeks 16 is presented.
100. Height Velocity at Week 52 [ Time Frame: week 52 ]
     Height velocity was the change in height per year. The height velocity was calculated as the difference between current height and baseline divided by by time duration in days between those measurement time points and multiplied by 365 days. Height velocity calculated at Week 52 are presented.
101. Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 16 [ Time Frame: Week 0, week 16 ]
     C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment [C-CASA]) is an interview-based rating scale to systematically assess suicidality, suicidal behaviour, suicidal ideation. Suicidality: emergence of any suicidal ideation or suicidal behaviour. Suicidal behaviour: when response is "yes" for any of the questions- actual attempt to suicide, engaged in non-suicidal self-injurious behaviour, interrupted attempt, aborted attempt, preparatory acts. Suicidal ideation: when response is "yes" for any of the questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide. This outcome measure presents number of participants with "suicidal ideation or suicidal behaviour on C-SSRS" assessed at baseline (week 0), week 16. The questionnaire was not used in Part B due to the young age of the participants in Part B.
102. Part A: Number of Participants With Change in Columbia Suicidality Severity Rating Scale (C-SSRS) at Week 52 [ Time Frame: Week 0, week 52 ]
     C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment [C-CASA]) is an interview-based rating scale to systematically assess suicidality, suicidal behaviour, suicidal ideation. Suicidality: emergence of any suicidal ideation or suicidal behaviour. Suicidal behaviour: when response is "yes" for any of the questions- actual attempt to suicide, engaged in non-suicidal self-injurious behaviour, interrupted attempt, aborted attempt, preparatory acts. Suicidal ideation: when response is "yes" for any of the questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide. This outcome measure presents number of participants with "suicidal ideation or suicidal behaviour on C-SSRS" assessed at baseline (week 0), week 52. The questionnaire was not used in Part B due to the young age of the participants in Part B.
103. Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 16 [ Time Frame: Week 0, week 16 ]
     Change in Patient Health Questionnaire 9 (PHQ-9) was evaluated from baseline (week 0) to weeks 16. The PHQ-9 questionnaire is a 9-item depression module included in the patient health questionnaire, a self-administered diagnostic tool used for assessment of mental disorders. The PHQ-9 total score ranges from 0-27; total scores of 1-4 represent no depression, total scores of 5-9 represent mild depression, total scores of 10-14 represent moderate depression, total scores of 15-19 represent moderately severe depression and total scores of 20-27 represent severe depression. The questionnaire was not used in Part B due to the young age of the participants in Part B.
104. Part A: Change in Patient Reported Health Questionnaire-9 (PHQ-9) From Baseline at Week 52 [ Time Frame: Week 0, week 52 ]
     Change in Patient Health Questionnaire 9 (PHQ-9) was evaluated from baseline (week 0) to weeks 52. The PHQ-9 questionnaire is a 9-item depression module included in the patient health questionnaire, a self-administered diagnostic tool used for assessment of mental disorders. The PHQ-9 total score ranges from 0-27; total scores of 1-4 represent no depression, total scores of 5-9 represent mild depression, total scores of 10-14 represent moderate depression, total scores of 15-19 represent moderately severe depression and total scores of 20-27 represent severe depression. The questionnaire was not used in Part B due to the young age of the participants in Part B.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Novo Nordisk Investigational Site

Santa Monica, California, United States, 90404

United States, Maryland

Novo Nordisk Investigational Site

Baltimore, Maryland, United States, 21229

United States, New York

Novo Nordisk Investigational Site

Buffalo, New York, United States, 14203

Novo Nordisk Investigational Site

Mineola, New York, United States, 11501

United States, Ohio

Novo Nordisk Investigational Site

Columbus, Ohio, United States, 43235

Australia, New South Wales

Novo Nordisk Investigational Site

Camperdown, New South Wales, Australia, 2050

Australia, Victoria

Novo Nordisk Investigational Site

Parkville, Victoria, Australia, 3052

Canada, Alberta

Novo Nordisk Investigational Site

Calgary, Alberta, Canada, T3B 6A8

Canada, Quebec

Novo Nordisk Investigational Site

Montreal, Quebec, Canada, H4A 3J1

France

Novo Nordisk Investigational Site

ANGERS cedex 09, France, 49033

Novo Nordisk Investigational Site

Bordeaux, France, 33076

Novo Nordisk Investigational Site

Brest, France, 29609

Novo Nordisk Investigational Site

BRON cedex, France, 69677

Novo Nordisk Investigational Site

Haguenau, France, 67504

Novo Nordisk Investigational Site

Lille, France, 59037

Novo Nordisk Investigational Site

MARSEILLE Cédex 05, France, 13385

Novo Nordisk Investigational Site

MONTPELLIER cedex 05, France, 34295

Novo Nordisk Investigational Site

Nice, France, 06200

Novo Nordisk Investigational Site

Paris, France, 75012

Novo Nordisk Investigational Site

Paris, France, 75015

Novo Nordisk Investigational Site

Rouen, France, 76031

Novo Nordisk Investigational Site

Toulouse cedex 9, France, 31059

Italy

Novo Nordisk Investigational Site

Fiumicino, Italy, 00050

Novo Nordisk Investigational Site

Milano, Italy, 20132

Novo Nordisk Investigational Site

Padova, Italy, 35128

Netherlands

Novo Nordisk Investigational Site

Rotterdam, Netherlands, 3015 CN

New Zealand

Novo Nordisk Investigational Site

Grafton, New Zealand, 1023

Turkey

Novo Nordisk Investigational Site

Ankara, Turkey, 06010

Novo Nordisk Investigational Site

Istanbul, Turkey, 34093

Novo Nordisk Investigational Site

Istanbul, Turkey, 34890

Novo Nordisk Investigational Site

Samsun, Turkey, 55139

Novo Nordisk Investigational Site

Trabzon, Turkey, 61080

Sponsors and Collaborators

Novo Nordisk A/S

  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:

Study Protocol  [PDF] March 25, 2021

Statistical Analysis Plan  [PDF] December 14, 2020

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

Publications of Results:

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.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02527200
• Other Study ID Numbers: NN8022-4179; 2014-004415-37 ( EudraCT Number ); U1111-1162-7884 ( Other Identifier: WHO ); NL54145.078.15 ( Other Identifier: CCMO )
• First Posted: August 18, 2015
• Results First Posted: February 3, 2022
• Last Update Posted: November 21, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prader-Willi Syndrome; Nutrition Disorders; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overnutrition; Liraglutide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists