E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prader-Willi-like phenotype |
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E.1.1.1 | Medical condition in easily understood language |
Prader-Willi-like syndrome |
Prader-Willi-like syndroom |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018747 |
E.1.2 | Term | Growth hormone |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects and safety of GH treatment on body composition, motor development, growth, glucose metabolism, serum lipids, cognition, behaviour, bone mineral density, and quality of life in children with PWL. To investigate the baseline clinical characteristics and underlying (epi)genetic causes of children with PWL and their relation to the effects and safety of GH treatment. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effects and safety of GH treatment on motor development, growth, glucose metabolism, serum lipids, cognition, behaviour, bone mineral density, and quality of life in children with PWL. To investigate the baseline clinical characteristics and underlying (epi)genetic causes of children with PWL and their relation to the effects and safety of GH treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Prader-Willi-like phenotype, according to the PWL criteria (see below), or with a proven molecular diagnosis of a uniparental disomy of chromosome 14 (mUPD14), or a mutation or duplication in the 15q11.2-q13 region (PWS-critical region). - Absence of a molecular diagnosis of PWS. This includes a type 1 (from breakpoint 1 to breakpoint 4) or type 2 (from breakpoint 2 to breakpoint 4) deletion, a uniparental disomy or imprinting center defect of the 15q11.2-q13 region. - Age: o Boys: 4 to 16 years o Girls: 4 to 14 years. - Written informed consent.
PWL criteria: The PWL phenotype is present in case of the following symptoms: • Hyperphagia and/or rapid weight gain between the ages of 1 and 8 years AND • Developmental/psychomotor delay (IQ<85 and/or enrolment in a school for children with special needs) AND • One or more of the following symptoms: o Infantile central hypotonia o Behavioural problems (temper tantrums, (auto)aggression, autistic and/or obsessive compulsive behaviour o Poor speech o Vision abnormalities (e.g. myopia, esotropia) o Short stature (as defined by < -2SD-score, or -2SD relative to the target height) o Small hands and feet for height and/or age. N.B. Patients diagnosed with UPD14 or a mutation/duplication in the 15q11.2 (Prader-Willi critical) region do not have to meet the PWL-criteria. |
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E.4 | Principal exclusion criteria |
- Non-cooperative behavior - Extremely low dietary intake of less than the minimally required intake according to WHO - Use of medication to reduce weight - BMI > +4SD |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study parameter will be the difference of the change in body fat percentage between the treatment group and control group during the first six months after the start of the study, as assessed by the DXA scan. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Six months, twelve months, 24 months. |
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E.5.2 | Secondary end point(s) |
At baseline: - Clinical characteristics of PWL - (Epi)genetic abnormalities found in the subjects with PWL - Baseline serum IGF-1 levels and GH peak levels during a GH stimulation test (clonidine test).
A difference between the change during the first six months of the study in the treatment versus the control group, in: - Height, weight, head circumference - Resting Energy Expenditure - Lean body mass - Laboratory parameters: glucose metabolism, serum lipids, thyroid hormone levels, IGF-I and IGF binding proteins, ghrelin. - Blood pressure - Sleep-related breathing disorders. - Cognition, behaviour and social emotional development
A difference between measurements at the start of the GH treatment and measurements after twelve and 24 months in all subjects: - Body fat percentage - Height, weight, head circumference, sitting height, arm span, length of foot, tibia and hand - Resting Energy Expenditure - Lean body mass - Laboratory parameters: glucose metabolism, serum lipids, thyroid hormone levels, IGF-I and IGF binding proteins, ghrelin. - Blood pressure - Sleep-related breathing disorders. - Cognition, behaviour and social emotional development |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Six months, twelve months, 24 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |