E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10003018 |
E.1.2 | Term | Appetite and general nutritional disorders |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036476 |
E.1.2 | Term | Prader-Willi syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10003022 |
E.1.2 | Term | Appetite disorders |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 evaluate the safety and tolerability of one dose of AZP-531 adjusted for bodyweight (2, 3 or 4 mg) administered over 2 weeks as daily subcutaneous injection. |
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E.2.2 | Secondary objectives of the trial |
To evaluate effects of AZP-531 after 2 weeks of administration on fullness/satiety and appetite/prospective food consumption as assessed by Numerical Rating Scales (NRS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients with genetically confirmed diagnosis of Prader-Willi Syndrome using standard DNA methylation test or fluorescent in situ hybridization
• Patients aged 16 years to 40 years old inclusive initially
o Patients aged 12 years old to less than 16 years old after formal decision of the Data Monitoring Committee
• Have evidence of increased appetite or hyperphagia, as judged by the investigator
• Patients on well-balanced controlled diet and on a regular exercise program as recommended in common clinical practice for this patient population
• Women of Child Bearing Potential (WCBP) must have a negative pregnancy test on admission to the study center
• All WCBP, sexually active male subjects, and all partners of subjects should agree to use adequate methods of birth control (diaphragm, condoms with spermicide…) throughout the study and for 30 days after the last dose of study drug
• Adequate renal function, defined as serum creatinine inferior or equal to 1.5 x Upper Limit of Normal (ULN) and urine protein/creatinine ratio <0.2
• Adequate hepatic function, defined as total bilirubin inferior or equal to 1.5 x ULN and Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) levels inferior or equal to 3 x ULN
• Growth hormone treatment will be permitted if doses have been stable for at least 1 month prior to screening
• Psychotropic treatment will be permitted and should be stable at least 1 month prior to screening
• Any other treatment including thyroid hormones should be stable for at least 1 month prior to screening
• Informed consent signed by the patient, parent or legal guardian, as appropriate
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E.4 | Principal exclusion criteria |
• History of chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or suspected alcohol abuse
• Type 1 diabetes
• Insulin treatment
• Use of weight loss agents or drugs known to affect appetite (including GLP-1 analogs) within 2 months prior to screening
• Co-morbid condition or disease (such as respiratory disease or psychiatric disorder) diagnosed less than 1 month prior to screening
• Co-morbid condition or disease or abnormal laboratory finding that would in the investigator judgment increase the subject risk to participating in this study and that will not allow the patient to complete the study
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs
• Participation in a clinical trial with an investigational agent within 2 months prior to screening
• Clinically significant abnormalities on ECG at screening
• Pregnant or lactating woman
• History of hypersensitivity to drugs with a similar chemical structure or class as AZP-531 (Acylated Ghrelin and Unacylated Ghrelin)
• Unwillingness or inability to follow the procedures outlined in the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of safety will be based on patients who have received at least one dose of study medication. Individual and summary statistics including mean, median, standard-deviation (SD) and range will be presented in tabular form by treatment group for vital signs and clinical laboratory data.
Adverse events will be tabulated and summarised according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA) and presented using the total number of AEs and the total number and percent of patients who experienced an AE per treatment group.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs will be collected from the signature of informed consent.
Safety laboratory evaluation will be performed at screening (D-2) and at the end of treatment period (D14)
Vital signs will be obtained at screening (D-2), Baseline (D-1) and at the end of treatment period (D14)
Waist Circumference, Weight, Height and BMI will be measured (derived from weight and height for BMI) at Baseline (D-1) and at the end of treatment period (D14) except for Height (only D-1) |
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E.5.2 | Secondary end point(s) |
The Numeric Rating Scales: fullness/satiety and appetite/prospective food consumption will be presented descriptively by time (before meal, just after meal, 120 minutes after meal), meal (breakfast, lunch), visit (D-1, D1, D14) and treatment.
Analysis of covariance (ANCOVA) or analysis of variance (ANOVA) will be performed at Day 14 for the afforded mentioned parameters. The model will include the parameter at baseline (when appropriate), the stratification variables and the treatment group. Key interactions will also be included to explore subgroup effect (e.g. Age Group-by-Treatment, Genetic Subtype-by-Treatment).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Numerical Rating Scales will be administered to patients at baseline (D-1), first day of treatment (D1) and at the end of treatment period (D14) |
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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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |