Genetic DisorderPhase 3NCT01927861
Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
A Phase 3 study testing somatropin in people with Genetic Disorder and Noonan Syndrome, run by Novo Nordisk A/S at 27 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- Genetic Disorder, Noonan Syndrome
- What is being tested?
- somatropin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 27 sitesJapan
- Study dates
- 19 Aug 2013to 12 Jul 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
Japan27 sites
Novo Nordisk Investigational Site
Asahikawa, Hokkaido, 078-8510
Novo Nordisk Investigational Site
Fukuoka, 812-8582
Novo Nordisk Investigational Site
Fukuoka, 830-0011
Novo Nordisk Investigational Site
Iruma-gun, Saitama, 350 0495
Novo Nordisk Investigational Site
Kanagawa, 216-8511
Novo Nordisk Investigational Site
Kanagawa, 232-8555
Novo Nordisk Investigational Site
Kyoto, 602-8566
Novo Nordisk Investigational Site
Maebashi-shi, Gunma, 371-8511
Novo Nordisk Investigational Site
Miyazaki, 889-1692
Novo Nordisk Investigational Site
Nagoya, Aichi, 467-8602
Novo Nordisk Investigational Site
Niigata-shi, Niigata, 951 8520
Novo Nordisk Investigational Site
Ōita, 879-5593
Novo Nordisk Investigational Site
Osaka, 534-0021
Novo Nordisk Investigational Site
Osaka, 594-1101
Novo Nordisk Investigational Site
Saitama-city, Saitama, 336-8522
Novo Nordisk Investigational Site
Saitama-shi, Saitama, 330-8777
Novo Nordisk Investigational Site
Sapporo, Hokkaido, 065-8611
Novo Nordisk Investigational Site
Sendai-shi, Miyagi, 980 8574
Novo Nordisk Investigational Site
Shizuoka, 431-3192
Novo Nordisk Investigational Site
Tochigi, 329-0498
Novo Nordisk Investigational Site
Tokyo, 113-8519
Novo Nordisk Investigational Site
Tokyo, 113-8655
Novo Nordisk Investigational Site
Tokyo, 157 8535
Novo Nordisk Investigational Site
Tokyo, 160-8582
Novo Nordisk Investigational Site
Tokyo, 162-8666
Novo Nordisk Investigational Site
Tokyo, 183-8561
Novo Nordisk Investigational Site
Zentsuji, Kagawa, 765-8507
About this study
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
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.
- Conditions
- Genetic Disorder, Noonan Syndrome
- Being tested
- somatropin
- Medical subject headings
- Genetic Diseases, Inborn, Noonan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
somatropinDrug
Administered subcutaneously (s.c., under the skin) in a daily regimen for at least 104 weeks. Subject will be offered to continue treatment for another 104 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 0.033 mg/kg/day | Experimental | Not described Receives: Drug: somatropin |
| 0.066 mg/kg/day | Experimental | Not described Receives: Drug: somatropin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Height SDS (Japanese National Reference Data)
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.
Measured: Baseline, week 104
Secondary outcomes (66)
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) 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.
Measured: Baseline to week 52
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 104) and height at week 52 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.
Measured: Week 52 to week 104
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days.
Measured: Baseline to week 52
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 104) and height at week 52 divided by time between those measurement time points and multiplied by 365 days.
Measured: Week 52 to week 104
Incidence of Treatment Emergent Adverse Events
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.
Measured: During 104 weeks of treatment
Change in IGF-I (Insulin-like Growth Factor-I)
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.
Measured: Baseline, week 104
Change in HbA1c (Glycosylated Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Monocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Basophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL (low-density lipoprotein) cholesterol and HDL (high-density lipoprotein) cholesterol. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (r-GTP) and alkaline phosphatase. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
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.
Measured: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - creatinine. Missing values were imputed using the LOCF method.
Measured: Baseline, Week 104
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
AUC (area under the curve) 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 104 was evaluated based on the oral glucose tolerance test (OGTT). Change from baseline results are presented as 'ratio to baseline'.
Measured: Baseline, week 104
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
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 104 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.
Measured: Baseline, week 104
Change in Bone Age
X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the radius, ulna and short bones (RUS) score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age.
Measured: Baseline, week 104
Change in Bone Age/Chronological Age
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.
Measured: Baseline, week 104
Yearly Change in Bone Age/Change in Chronological Age
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 baseline (week 0) in bone age/change in chronological age was presented.
Measured: Baseline, week 52
Yearly Change in Bone Age/Change in Chronological Age
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 52 in bone age/change in chronological age was presented.
Measured: Week 52, week 104
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
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.
Measured: Baseline, week 104
Change in Vital Signs (Pulse)
Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse.
Measured: Baseline, week 104
Change in Urinalysis (Protein, Glucose and Occult Blood)
The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 104 and categorised as negative, trace, 1+, 2+ and 3+. Missing values were imputed using the LOCF method. Number of participants in each category at baseline and week 104 are presented.
Measured: Baseline, week 104
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: Prothrombin time and APTT (activated partial thromboplastin time). Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in ECG
The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 104 and categorised as normal, abnormal NCS (not clinically significant) or abnormal CS (clinically significant). Number of participants in each ECG category at baseline and week 104 are presented. Missing values were imputed using the LOCF method.
Measured: Baseline, week 104
Change in Height SDS (Japanese National Reference Data)
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.
Measured: Baseline, week 208
Change in Height SDS (Noonan Syndrome Reference Data in Japanese)
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.
Measured: Baseline, week 208
Height Velocity
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 156) and height at week 104 divided by time between those measurement time points and multiplied by 365 days. Missing values were imputed using the LOCF method.
Measured: Week 104 to week 156
Height Velocity
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.
Measured: Week 156 to week 208
Height Velocity SDS
Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 156) and height at week 104 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.
Measured: Week 104 to week 156
Height Velocity SDS
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.
Measured: Week 156 to week 208
Incidence of Treatment Emergent AEs
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.
Measured: Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)
Change in IGF-I
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.
Measured: Baseline, week 208
Change in HbA1c
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, Week 208
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Monocytes)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Haematology: Basophils)
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
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.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
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.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
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.
Measured: Baseline, week 208
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - creatinine. Missing values were imputed using the LOCF method.
Measured: Baseline, week 208
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
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'.
Measured: Baseline, week 208
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
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'.
Measured: Baseline, week 208
Change in Bone Age
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.
Measured: Baseline, week 208
Change in Bone Age/Chronological Age
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.
Measured: Baseline, week 208
Yearly Change in Bone Age/Change in Chronological Age
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 104 in bone age/change in chronological age was presented.
Measured: Week 104, week 156
Yearly Change in Bone Age/Change in Chronological Age
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.
Measured: Week 156, week 208
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
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.
Measured: Baseline, week 208
Change in Vital Signs (Pulse)
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.
Measured: Baseline, week 208
Change in Urinalysis (Protein, Glucose and Occult Blood)
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.
Measured: Baseline, week 208
Change in Blood Coagulation Test (Prothrombin Time and APTT)
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.
Measured: Baseline, week 208
Change in ECG
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.
Measured: Baseline, week 208
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2013 (estimated)
- Study start19 Aug 2013
- Primary completion12 Jul 2018
- Study completion12 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Genetic DisorderStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01927861
- Sponsor's protocol ID
- GHLIQUID-4020
- Other IDs
- U1111-1131-5892, JapicCTI-132336
- Status last verified
- Jul 2020
- First submitted
- 20 Aug 2013
- Last updated
- 10 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 32269181Ozono 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.
PubMed 29109363Muroya K, Kawai M, Yamagishi H, Endo T, Pietropoli A, Ferran JM, Horikawa R. Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study. Endocr J. 2026 Feb 2;73(2):229-241. doi: 10.1507/endocrj.EJ25-0116. Epub 2025 Nov 22.
PubMed 41285480
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01927861
- Acronym / sponsor ID
- GHLIQUID-4020
- Conditions
- Genetic Disorder, Noonan Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2013 (actual)
- Primary completion
- 12 Jul 2018 (actual)
- Study completion
- 12 Jul 2018 (actual)
- First posted
- 23 Aug 2013 (estimated)
- Results
- Posted 14 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.033 mg/kg/day | Experimental | Drug: somatropin |
| 0.066 mg/kg/day | Experimental | Drug: somatropin |
Who may qualify
- Ages
- 3 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| somatropinAdministered subcutaneously (s.c., under the skin) in a daily regimen for at least 104 weeks. Subject will be offered to continue treatment for another 104 weeks. | Drug | 0.033 mg/kg/day, 0.066 mg/kg/day |
Primary outcome
Change in Height SDS (Japanese National Reference Data)
Time frame: 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.
66 secondary outcomes
Height Velocity SDS
Time frame: Baseline to week 52
Height Velocity SDS
Time frame: Week 52 to week 104
Height Velocity
Time frame: Baseline to week 52
Height Velocity
Time frame: Week 52 to week 104
Incidence of Treatment Emergent Adverse Events
Time frame: During 104 weeks of treatment
Change in IGF-I (Insulin-like Growth Factor-I)
Time frame: Baseline, week 104
Change in HbA1c (Glycosylated Haemoglobin)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Monocytes)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Haematology: Basophils)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Time frame: Baseline, week 104
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
Time frame: Baseline, Week 104
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
Time frame: Baseline, week 104
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
Time frame: Baseline, week 104
Change in Bone Age
Time frame: Baseline, week 104
Change in Bone Age/Chronological Age
Time frame: Baseline, week 104
Yearly Change in Bone Age/Change in Chronological Age
Time frame: Baseline, week 52
Yearly Change in Bone Age/Change in Chronological Age
Time frame: Week 52, week 104
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Time frame: Baseline, week 104
Change in Vital Signs (Pulse)
Time frame: Baseline, week 104
Change in Urinalysis (Protein, Glucose and Occult Blood)
Time frame: Baseline, week 104
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Time frame: Baseline, week 104
Change in ECG
Time frame: Baseline, week 104
Change in Height SDS (Japanese National Reference Data)
Time frame: Baseline, week 208
Change in Height SDS (Noonan Syndrome Reference Data in Japanese)
Time frame: Baseline, week 208
Height Velocity
Time frame: Week 104 to week 156
Height Velocity
Time frame: Week 156 to week 208
Height Velocity SDS
Time frame: Week 104 to week 156
Height Velocity SDS
Time frame: Week 156 to week 208
Incidence of Treatment Emergent AEs
Time frame: Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)
Change in IGF-I
Time frame: Baseline, week 208
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32269181Horikawa 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.
- Results publication: PubMed 29109363Ozono 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.
- Derived from this study: PubMed 41285480Muroya K, Kawai M, Yamagishi H, Endo T, Pietropoli A, Ferran JM, Horikawa R. Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study. Endocr J. 2026 Feb 2;73(2):229-241. doi: 10.1507/endocrj.EJ25-0116. Epub 2025 Nov 22.
- Clinical Trials at Novo NordiskLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Registry (GCR, 1452) study director
Novo Nordisk A/S
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing somatropin in people with Genetic Disorder and Noonan Syndrome, run by Novo Nordisk A/S at 27 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Height SDS (Japanese National Reference Data) (time frame: Baseline, week 104). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01927861, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2020.