Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
- Registration Number
- NCT01927861
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial is conducted in Asia. The aim of the trial is to investigate the long-term efficacy and safety of two doses of NN-220 (somatropin) in short stature due to Noonan syndrome.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 51
- Japanese children with Noonan syndrome clinically diagnosed in one of the following ways: 1. Clinically diagnosed by at least two medical experts using van der Burgt score list, 2. Clinically diagnosed by one medical expert using van der Burgt score list and diagnosed by result of genetic testing for Noonan syndrome, 3. Clinically diagnosed by one medical expert using van der Burgt score list and diagnosed by the same medical expert based on the results of centralised evaluation of facial change using van der Burgt score list
- Height SDS (standard deviation score): -2 SDS or below (according to the Japanese reference data)
- Age: boys 3 to below 11 years, girls 3 to below 10 years
- Height records must be available within the period between 40 and 64 weeks prior to Visit 1 (screening)
- Prepubertal children (definition for girls breast and pubes of Tanner stage is I, and none of menses, and for boys testicular volume below 4 mL, and pubes and penis of Tanner stage is I)
- Children with known or suspected hypersensitivity against human growth hormone (hGH) or related products (including any components of the trial products)
- Children with diabetic type diagnosed with the Japanese Diabetes Society Classification
- Children with history or presence of active malignancy
- Children who have received GH (growth hormone) treatment
- Children who have received systemic administration of the following medications within two years prior to Visit 1 (screening): Thyroid hormone (except replacement therapy), antithyroid hormone, androgen, oestrogen, progesterone, anabolic steroid, adrenocortical steroid treatment period for at least 13 weeks), derivative of gonadotropin releasing hormone and somatomedin C (IGF-I)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.033 mg/kg/day somatropin - 0.066 mg/kg/day somatropin -
- Primary Outcome Measures
Name Time Method Change in Height SDS (Japanese National Reference Data) Baseline, week 104 Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline height SDS as a covariate. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the last observation carried forward (LOCF) method.
- Secondary Outcome Measures
Name Time Method Change in Clinical Laboratory Tests (Haematology: Haemoglobin) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Basophils) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Change in Blood Coagulation Test (Prothrombin Time and APTT) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: prothrombin time and APTT. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Haematocrit) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Lymphocytes) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Monocytes) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Incidence of Treatment Emergent Adverse Events During 104 weeks of treatment A treatment emergent adverse event (TEAE; for the pivotal phase) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than the date of visit 12 (104 weeks; end of pivotal phase). For withdrawal participants (if any), an adverse event with onset date no later than 7 days after the last day of NN-220 treatment was included.
Change in IGF-I (Insulin-like Growth Factor-I) Baseline, week 104 Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 104 weeks of treatment. Missing values were imputed using the LOCF method.
Change in HbA1c (Glycosylated Haemoglobin) Baseline, week 104 Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment.
Change in Clinical Laboratory Tests (Haematology: Erythrocytes) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes) Baseline, Week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL cholesterol and HDL cholesterol. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Biochemistry: Total Protein) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Change in Bone Age Baseline, week 208 X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age.
Yearly Change in Bone Age/Change in Chronological Age Week 156, week 208 X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 156 in bone age/change in chronological age was presented.
Height Velocity SDS Week 156 to week 208 Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 208) and height at week 156 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.
Height Velocity Week 156 to week 208 Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 208) and height at week 156 divided by time between those measurement time points and multiplied by 365 days. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Neutrophils) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - blood urea nitrogen, sodium, potassium, chloride, total calcium and phosphorus. Missing values were imputed using the LOCF method.
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure) Baseline, week 208 Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure. Missing values were imputed using the LOCF method.
Change in IGF-I Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 208 weeks of treatment. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Eosinophils) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT Baseline, week 208 AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Change in Vital Signs (Pulse) Baseline, week 208 Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse. Missing values were imputed using the LOCF method.
Change in ECG Baseline, week 208 The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 208 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - AST, ALT, r-GTP and alkaline phosphatase. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Biochemistry: Creatinine) Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - creatinine. Missing values were imputed using the LOCF method.
Change in Bone Age/Chronological Age Baseline, week 208 X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age/chronological age.
Change in Urinalysis (Protein, Glucose and Occult Blood) Baseline, week 208 The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 208 and categorised as negative, trace, 1+, 2+ and 3+. Number of participants in each category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.
Change in Height SDS (Japanese National Reference Data) Baseline, week 208 Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.
Change in Height SDS (Noonan Syndrome Reference Data in Japanese) Baseline, week 208 Height SDS was calculated using the formula: Z=\[(value/M)\^L-1\]/(S\*L); where L, M and S are skewness (L), median (M) and coefficient of variation (S) of Japanese Noonan syndrome' height 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. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.
Incidence of Treatment Emergent AEs Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period) A treatment emergent AE (TEAE) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than 7 days after the last day of NN-220 treatment.
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT Baseline, week 208 AUC of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Change in HbA1c Baseline, week 208 Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment.
Trial Locations
- Locations (1)
Novo Nordisk Investigational Site
🇯🇵Zentsuji, Kagawa, Japan