French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome

Study Overview
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Brief Summary
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This is a non-interventional registry of children treated with Norditropin® for short stature due to Noonan Syndrome (NS). This study aims to provide data on long-term growth evolution and safety of Norditropin® as well as Health Related Quality of Life (HRQoL) data. This registry will include the entirety of children treated with Norditropin® for short stature due to NS over the inclusion period. The decision to initiate treatment with commercially available Norditropin® is made by the patient/parents/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study.

Official Title
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French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome

Conditions
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Noonan Syndrome

Intervention / Treatment
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* Drug: Norditropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a clinical and/or genetic diagnosis of NS Patients who are treated with Norditropin® (already treated or initiating) and who are followed in a participating center The decision to initiate treatment with commercially available Norditropin® has been made by the patient/parents/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study Exclusion Criteria: Patients/Parents/LAR opposed to the collection and processing of their children's medical data Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Incident patients<br>Children initiated Norditropin® upon their inclusion in the study but independently from the decision to participate in this study | Drug: Norditropin<br>* Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.<br>* Other names: Somatropin;|
| Prevalent patients - finished growth upon inclusion<br>Children were already treated with Norditropin® before their inclusion in the study and finished their growth upon their inclusion. Data collected retrospectively from medical records | Drug: Norditropin<br>* Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.<br>* Other names: Somatropin;|
| Prevalent patients - not finished growth upon inclusion<br>Children were already treated with Norditropin® before their inclusion in the study and did not finish their growth upon inclusion. Data collected both retrospectively and prospectively | Drug: Norditropin<br>* Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.<br>* Other names: Somatropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in height standard deviation score | Measured in standard deviation scores (SDS) ranging from -10 to +10 | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse drug reactions (ADR) | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Number of serious adverse drug reactions (SADR) | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Number of serious adverse events (SAE) | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Number of adverse events (AE) | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Education | Number of participants is measured under the categorical variables - standard education, education with assistance and educational measures | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| School level | Number of participants is measured under the variables - preschool, elementary school, secondary school and high school | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Educational measures | Number of participants is measured under the categorical variables - physiotherapy, psychomotricity, occupational therapy and speech therapy | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Tanner stage | Measured as units on scale. 3 sub-scales used - Pubic hair scale, Female breast development scale and Male external genitalia scale. Tanner stages range from Stage 1 to 5 with Tanner Stage 1 corresponding to the pre-pubertal form and Tanner Stage 5 corresponding to the final adult form | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in pulse rate | Measured in beats per minute | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in diastolic blood pressure | Measured in millimeters of Mercury (mm Hg) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in systolic blood pressure | Measured in mm Hg | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in corrected QT-interval (Electrocardiogram) | Measured in millisecond (msec) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in echocardiogram parameters (mm) | Change in Left ventricular interventricular septal maximum thickness in diastole and Left ventricular end diastolic diameter is measured in millimeter (mm) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in echocardiogram parameters (%) | Change in Left Ventricular Fractional Shortening (LVFS) and Left Ventricular Ejection Fraction (LVEF) is measured in percentage (%) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in echocardiogram parameters (cm/s) | Change in Diastolic function (Ea and Aa) measured in centimeters per second (cm/s) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in complete blood count (CBC) (g/dL) | Change in Haemoglobin (Hb) measured in grams per deciLiter (g/dL) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in CBC (G/L) | Change in white blood cells, lymphocytes, monocytes and platelets measured in grams per liter (G/L) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Insulin-like growth factor 1 (IGF-1) level (ng/ml) | Measured in nanograms per milliliter (ng/ml) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in IGF-1 level (SDS) | Measured in SDS | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Haemoglobin A1c (HbA1c) level | Measured in % | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting insulin level | Measured in milligrams per deciliter (mg/dL) or milli-international units per litre (mUI/L) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting blood glucose level | Measured in mg/dL or g/L or millimoles per litre (mmol/L) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting total cholesterol | Measured in mg/dl or g/L or mmol/L | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting triglycerides | Measured in mg/dL or g/L or mmol/L | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting high-density lipoproteins (HDL) cholesterol | Measured in mg/dL or g/L or mmol/L | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting low-density lipoproteins (LDL) cholesterol | Measured in mg/dL or g/L or mmol/L | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in fasting total cholesterol/HDL ratio | Ratio of fasting total cholesterol and HDL | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in inhibin B | Measured in picograms per milliliter (pg/mL) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Anti-Müllerian Hormone (AMH) | Measured in milligrams per milliliter (mg/mL) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Luteinizing Hormone (LH) (female from 8 years old and male from 9 years old) | Measured in mg/mL | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Follicle-Stimulating Hormone (FSH) (female from 8 years old and male from 9 years old) | Measured in International units per litre (UI/L) or mUI/mL | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in oestradiol (female from 8 years old and male from 9 years old) | Measured in pg/mL | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in testosterone (female from 8 years old and male from 9 years old) | Measured in ng/mL | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in dose of Norditropin® treatment | Measured in milligram per kilogram per day (mg/kg/day) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Frequency of injections of Norditropin® treatment per week | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Number of modifications (change in dosage/ temporary stop) | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Reasons for treatment modifications | Measured in number of participants under categorical variable - safety (occurrence of ARs or AEs), growth too fast, growth too slow, patient's or parents/LAR choice; and other | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Duration of temporary stop | Measured in months | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Total duration of Norditropin® treatment | Measured in years | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Total cumulative dose of Norditropin® treatment | Measured in mg/kg | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Type and number of concomitant treatments | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Type and number of concomitant treatments linked to an adverse event | Count of events | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in weight | Measured in SDS | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in body mass index (BMI) | Measured in kilogram per square metre (kg/m^2) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in bone age | Measured in year | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in height velocity (cm/year) | Measured in cm/year | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in height velocity (SDS/year) | Measured in SDS/year | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Type and number of NS comorbidities | Number of participants measured under categorical variables - Cardiac defects including pulmonary valve stenosis and hypertrophic cardiomyopathy, Orthopaedic issues (pectus, scoliosis) and Anorchia in males | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) | 
| Change in Health-Related Quality of Life (HRQoL) score (PedsQL) | PedsQL score used to assess the HRQoL, ranges from 1 to 100 (higher scores indicate better HRQoL) | From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years) |