Primary outcomeLeast squares mean· Baseline, week 104
Change in Height SDS (Japanese National Reference Data)
| Group | Value (Standard deviation score) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 0.84 | 0.09 |
| NN-220 0.066 mg/kg/Day | 1.47 | 0.09 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataInvestigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCTNCT01927861 (opens ClinicalTrials.gov in a new tab)Other idGHLIQUID-4020Other idU1111-1131-5892Other idJapicCTI-132336
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 51 participants (actual)
- Sponsor
- Novo Nordisk A/S · Industry
- Design
- Randomized · Double masking
- Countries
1 country
Japan
- Start
- 19 Aug 2013
- Primary completion
- 12 Jul 2018
- Completion
- 12 Jul 2018
- First posted
- 23 Aug 2013 (estimated)
- Last update posted
- 10 Aug 2020
- Conditions
- Genetic Disorder · Noonan Syndrome
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2013201420152016201720182019
- Ph 3
Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT0192786119 Aug 2013 to 12 Jul 2018
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- somatropinDrug
Arms2
Experimental
0.033 mg/kg/day
Experimental
0.066 mg/kg/day
Primary outcomes1
Outcomes the sponsor listed as primary.
Change in Height SDS (Japanese National Reference Data)
Time frame · Baseline, week 104
Registry description
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 outcomes(20)
Height Velocity SDS
Time frame · Baseline to week 52
Registry description
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.
Height Velocity SDS
Time frame · Week 52 to week 104
Registry description
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.
Height Velocity
Time frame · Baseline to week 52
Registry description
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
Time frame · Week 52 to week 104
Registry description
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.
Incidence of Treatment Emergent Adverse Events
Time frame · During 104 weeks of treatment
Registry description
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)
Time frame · Baseline, week 104
Registry description
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)
Time frame · Baseline, week 104
Registry description
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)
Time frame · Baseline, week 104
Registry description
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)
Time frame · Baseline, week 104
Registry description
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 (Haematology: Haemoglobin)
Time frame · Baseline, week 104
Registry description
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: Haematocrit)
Time frame · Baseline, week 104
Registry description
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: Neutrophils)
Time frame · Baseline, week 104
Registry description
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 (Haematology: Lymphocytes)
Time frame · Baseline, week 104
Registry description
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)
Time frame · Baseline, week 104
Registry description
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
Time frame · Baseline, week 104
Registry description
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Haematology: Basophils)
Time frame · Baseline, week 104
Registry description
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Time frame · Baseline, week 104
Registry description
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.
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Time frame · Baseline, week 104
Registry description
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.
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
Time frame · Baseline, week 104
Registry description
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 Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Time frame · Baseline, week 104
Registry description
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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline to week 52
Height Velocity SDS
| Group | Value (Standard deviation score) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 2.80 | 1.13 |
| NN-220 0.066 mg/kg/Day | 5.01 | 1.92 |
Secondary outcomeMean· Week 52 to week 104
Height Velocity SDS
| Group | Value (Standard deviation score) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 0.58 | 1.59 |
| NN-220 0.066 mg/kg/Day | 2.65 | 1.76 |
Secondary outcomeMean· Baseline to week 52
Height Velocity
| Group | Value (Centimeters per year (cm/year)) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 7.88 | 0.87 |
| NN-220 0.066 mg/kg/Day | 9.90 | 1.49 |
Secondary outcomeMean· Week 52 to week 104
Height Velocity
| Group | Value (cm/year) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 6.20 | 0.95 |
| NN-220 0.066 mg/kg/Day | 7.99 | 1.20 |
Secondary outcomeNumber· During 104 weeks of treatment
Incidence of Treatment Emergent Adverse Events
| Group | Value (Events) |
|---|---|
| NN-220 0.033 mg/kg/Day | 265 |
| NN-220 0.066 mg/kg/Day | 306 |
Secondary outcomeMean· Baseline, week 104
Change in IGF-I (Insulin-like Growth Factor-I)
| Group | Value (Nanograms per milliliter (ng/mL)) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 90.4 | 65.5 |
| NN-220 0.066 mg/kg/Day | 159.1 | 88.0 |
Secondary outcomeMean· Baseline, week 104
Change in HbA1c (Glycosylated Haemoglobin)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| NN-220 0.033 mg/kg/Day | 0.14 | 0.18 |
| NN-220 0.066 mg/kg/Day | 0.13 | 0.20 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| 0.033 mg/kg/DayParticipants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase). | 0 / 25 | 9 / 25 | 24 / 25 |
| 0.066 mg/kg/DayParticipants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase). | 0 / 26 | 10 / 26 | 26 / 26 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies3
Studies that cite this trial.
More studies
3 studies on this page
PubMed tag: none · 2026
Long-term effectiveness and safety of daily growth hormone therapy in Japanese children with Noonan syndrome: a post-marketing surveillance study.
Muroya et al. 2026Endocrine journal
PMID 41285480PMC12895119DOI 10.1507/endocrj.ej25-0116PUB-41285480
Free to read · publisher termsCC BY-NC-ND
Indexing hint: Randomized controlled trial · 2020
Long-term efficacy and safety of two doses of Norditropin® (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients.
Horikawa et al. 2020Endocrine journalcited by 21
PMID 32269181DOI 10.1507/endocrj.ej19-0371PUB-32269181
Rights unknown
Indexing hint: Randomized controlled trial · 2018
Efficacy and safety of two doses of Norditropin® (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients.
Ozono et al. 2018Endocrine journalcited by 19
PMID 29109363DOI 10.1507/endocrj.ej17-0313PUB-29109363
Full text at the publisher
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 3 Years up to 10 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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)
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