E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity
(Prader-Willi syndrome) |
|
E.1.1.1 | Medical condition in easily understood language |
Abnormal or excessive body fat accumulation/excess proportion of total body fat
(Prader-Willi syndrome) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of liraglutide versus placebo on weight loss in obese paediatric subjects with Prader-Willi syndrome (PWS) at 16 weeks and versus no treatment at 52 weeks |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy of liraglutide versus placebo on glycaemic control in obese children and adolescents with PWS at 16 weeks and versus no treatment at 52 weeks.
2. To estimate the liraglutide steady state exposure in obese children and adolescents with PWS after 16 weeks of treatment.
3. To compare the safety of liraglutide versus placebo in obese children and adolescents with PWS at 16 weeks and versus no treatment at 52 weeks. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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
2. Confirmed diagnosis of PWS (by genetic testing)
3. Male or female, age at the time of signing informed consent:
– Part A: ≥ 12 and < 18 years
– Part B: ≥ 6 and < 12 years
4. Tanner stage 2−5 pubertal development for part A, and Tanner stage 1 for part B
5. BMI corresponding to ≥ 30 kg/m^2 for adults by international cut-off points and ≥ the 95th percentile for age and sex (for diagnosis of obesity)
6. Stable body weight during the previous 90 days before screening (< 10 kg self-reported weight change)
7. Testing has been performed to evaluate for adrenal insufficiency and documented in medical record |
|
E.4 | Principal exclusion criteria |
1. Type 1 diabetes mellitus (T1DM)
2. Type 2 diabetes mellitus (T2DM)
3. Calcitonin ≥ 50 ng/L
4. 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)
5. Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroids Carcinoma (MTC)
6. History of pancreatitis (acute or chronic)
7. 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)
8. Untreated adrenal insufficiency
9. Suggestive history of, or significant risk of gastroparesis (e.g. marked abdominalbloating post-meal, history of vomiting, severe constipation), as judged by the investigator |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in body mass index (BMI) standard deviation score (SDS)
2. Change in body mass index (BMI) standard deviation score (SDS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From baseline to 16 weeks
2. From baseline to 52 weeks |
|
E.5.2 | Secondary end point(s) |
1. Percent of subjects achieving ≥ 5% reduction in baseline BMI
2. Percent of subjects achieving ≥ 10% reduction in baseline BMI
Change in:
3. BMI
4. Body weight (kilogram (kg), pounds (lb) and percent (%))
5. Hyperphagia score:
a. total score and
b. hyperphagic behaviour, drive and severity score
6. Systolic and diastolic blood pressure
7. Glucose metabolism: glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. - 2.: At weeks 16 and 52
3. - 7.: From baseline to 16 and 52 weeks |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double-blind period followed by open-label period |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
European Union |
New Zealand |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 3 |