Clinical trial NCT01927861: Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
Official title: A 52-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Short Stature With Noonan Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Genetic Disorder
Noonan Syndrome
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2013-08-23
Enrollment: 51
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Change in Height SDS (Japanese National Reference Data)
timeFrame: Baseline, week 104
Secondary outcomes:
measure: Height Velocity SDS
timeFrame: Baseline to week 52
measure: Height Velocity SDS
timeFrame: Week 52 to week 104
measure: Height Velocity
timeFrame: Baseline to week 52
measure: Height Velocity
timeFrame: Week 52 to week 104
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: During 104 weeks of treatment
measure: Change in IGF-I (Insulin-like Growth Factor-I)
timeFrame: Baseline, week 104
measure: Change in HbA1c (Glycosylated Haemoglobin)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Haematocrit)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Neutrophils)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Monocytes)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Eosinophils)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Haematology: Basophils)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
timeFrame: Baseline, week 104
measure: Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
timeFrame: Baseline, Week 104
measure: Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
timeFrame: Baseline, week 104
measure: Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
timeFrame: Baseline, week 104
measure: Change in Bone Age
timeFrame: Baseline, week 104
measure: Change in Bone Age/Chronological Age
timeFrame: Baseline, week 104
measure: Yearly Change in Bone Age/Change in Chronological Age
timeFrame: Baseline, week 52
measure: Yearly Change in Bone Age/Change in Chronological Age
timeFrame: Week 52, week 104
measure: Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
timeFrame: Baseline, week 104
measure: Change in Vital Signs (Pulse)
timeFrame: Baseline, week 104
measure: Change in Urinalysis (Protein, Glucose and Occult Blood)
timeFrame: Baseline, week 104
measure: Change in Blood Coagulation Test (Prothrombin Time and APTT)
timeFrame: Baseline, week 104
measure: Change in ECG
timeFrame: Baseline, week 104
measure: Change in Height SDS (Japanese National Reference Data)
timeFrame: Baseline, week 208
measure: Change in Height SDS (Noonan Syndrome Reference Data in Japanese)
timeFrame: Baseline, week 208
measure: Height Velocity
timeFrame: Week 104 to week 156
measure: Height Velocity
timeFrame: Week 156 to week 208
measure: Height Velocity SDS
timeFrame: Week 104 to week 156
measure: Height Velocity SDS
timeFrame: Week 156 to week 208
measure: Incidence of Treatment Emergent AEs
timeFrame: Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)
measure: Change in IGF-I
timeFrame: Baseline, week 208
measure: Change in HbA1c
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
timeFrame: Baseline, Week 208
measure: Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Haematocrit)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Neutrophils)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Monocytes)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Eosinophils)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Haematology: Basophils)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
timeFrame: Baseline, week 208
measure: Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
timeFrame: Baseline, week 208
measure: Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
timeFrame: Baseline, week 208
measure: Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
timeFrame: Baseline, week 208
measure: Change in Bone Age
timeFrame: Baseline, week 208
measure: Change in Bone Age/Chronological Age
timeFrame: Baseline, week 208
measure: Yearly Change in Bone Age/Change in Chronological Age
timeFrame: Week 104, week 156
measure: Yearly Change in Bone Age/Change in Chronological Age
timeFrame: Week 156, week 208
measure: Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
timeFrame: Baseline, week 208
measure: Change in Vital Signs (Pulse)
timeFrame: Baseline, week 208
measure: Change in Urinalysis (Protein, Glucose and Occult Blood)
timeFrame: Baseline, week 208
measure: Change in Blood Coagulation Test (Prothrombin Time and APTT)
timeFrame: Baseline, week 208
measure: Change in ECG
timeFrame: Baseline, week 208
Other outcomes:
Locations:
city: Asahikawa, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Iruma-gun, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kyoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Maebashi-shi, Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Nagoya, Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Niigata-shi, Niigata
country: Japan
facility: Novo Nordisk Investigational Site
city: Oita
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Saitama-city, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Saitama-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Sendai-shi, Miyagi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shizuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tochigi
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Zentsuji, Kagawa
country: Japan
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Horikawa R, Ogata T, Matsubara Y, Yokoya S, Ogawa Y, Nishijima K, Endo T, Ozono K. Long-term efficacy and safety of two doses of Norditropin(R) (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients. Endocr J. 2020 Aug 28;67(8):803-818. doi: 10.1507/endocrj.EJ19-0371. Epub 2020 May 9.
citation: Ozono K, Ogata T, Horikawa R, Matsubara Y, Ogawa Y, Nishijima K, Yokoya S. Efficacy and safety of two doses of Norditropin(R) (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients. Endocr J. 2018 Feb 26;65(2):159-174. doi: 10.1507/endocrj.EJ17-0313. Epub 2017 Nov 7.