Short Stature Children Born Small for Gestational Age (SGA)
Conditions
Brief summary
The study compares 2 medicines used for the treatment of children who are born small and who stayed small: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Participants will either get somapacitan or Norditropin® - which treatment is decided by chance. Both participants and the study doctor will know which treatment the participants get. The study will last for 5 years. Participants will take either an injection once every week or once every day.
Interventions
DRUGSomapacitan
Somapacitan injected under the skin once a week.
DRUGNorditropin®
Norditropin® injected under the skin once a day.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Pre-pubertal children, boys: 1. age between 2.5 and 11.0 years at screening. 2. testes volume below 4 ml. * Pre-pubertal children, girls: 1. age between 2.5 and 10.0 years at screening. 2. Tanner stage 1 for breast development (no palpable glandular breast tissue). * Born small for gestational age (birth length and/or weight below -2 standard deviation scores) (according to national standards). * Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and gender at screening according to the standards of Centers for Disease Control and Prevention at screening. * Impaired height velocity defined as annualized height velocity below the 50th percentile for chronological age and gender according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening. * No prior exposure to growth hormone therapy or Insulin-like Growth Factor-I (IGF-I) treatment.
Exclusion criteria
* Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements. * Children with hormonal deficiencies including suspected or confirmed growth hormone deficiency according to local practise. * Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening. * Children requiring inhaled glucocorticoid therapy at a dose of greater than 400 μg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening. * Concomitant administration of other treatments that may have an effect on growth, e.g but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder. * Diagnosis of attention deficit hyperactivity disorder. * Prior history or presence of malignancy including intracranial tumours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height Velocity | Baseline (week 0); week 26 | Height velocity (HV) was derived from height measurements taken at baseline (week 0) and week 26 visit as: HV = (height at 26 weeks visit - height at baseline)/(time from baseline to 26 weeks visit in years). The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ratio of Bone Age Versus Chronological Age | Baseline (week 0); week 52 | Change in ratio of bone age (years) versus chronological age (years) from baseline (week 0) to week 52 is presented. X-rays of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. X-ray images were sent to a central imaging laboratory for evaluation. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 52 or last trial contact, whichever came first. |
| Change in Height Standard Deviation Score (HSDS) | Baseline (week 0); week 26 | Change in HSDS from baseline (week 0) to week 26 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. HSDS = \[(height/population median)\^skewness - 1\]/(skewness \* population standard deviation) where skewness, median and standard deviation is given by a reference growth table for the corresponding chronological age. The range for HSDS was -10 to +10. Negative scores indicated a height below the mean height for a child with the same age and gender, whereas positive scores indicated a height above the mean height for a child with the same age and gender. Positive value in change from baseline in HSDS indicated that HSDS was better than baseline HSDS In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first. |
| Change in Height Velocity Standard Deviation Score (HVSDS) | Baseline (week 0); week 26 | Change in HVSDS from baseline (week 0) to week 26 is presented. HVSDS was derived using Prader standards. HV SDS was calculated using the formula: HV SDS = (height velocity - mean)/standard deviation (SD), where height velocity was the height velocity variable measured, mean and SD of height velocity by gender and age for the reference population. The range for HVSDS was -10 to +10. Negative scores indicated a height velocity below the mean height velocity for a child with the same age and gender, whereas positive scores indicated a height velocity above the mean height velocity for a child with the same age and gender. Positive value in change from baseline in HVSDS indicated that HVSDS was better than baseline HVSDS. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first. |
| Change in Fasting Plasma Glucose | Baseline (week 0); week 26 | Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
| Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | Baseline (week 0); week 26 | Change in HOMA-B from baseline (week 0) to week 26 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin (picomoles per liter \[pmol/L\]) \* 1/6(microunit per milliliter \[µU/mL\]))/ FPG(mmol/L)-3.5). HOMA-beta score ranges from minus infinity to infinity (no limits). Higher score means better beta-cell function for HOMA-beta. Negative change from baseline (week 0) in HOMA-B indicated a worse outcome. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
| Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Baseline (week 0); week 26 | Change in HOMA-IR from baseline (week 0) to week 26 is presented. Insulin resistance is a condition in which cells fail to respond to normal actions of hormone in body. HOMA-IR is calculated using a participant's fasting plasma insulin and glucose levels. HOMA-IR = fasting serum insulin (micro international units per milliliter (μU/ml)) × fasting plasma glucose (millimoles per liter (mmol/l)) / 22.5. HOMA-IR scores are classified as follows: less than 1.0: considered insulin sensitive, 0.5-1.4: considered healthy, above 1.8: considered early insulin resistance; above 2.7 is considered significant insulin resistance. HOMA-IR score ranges from 0-infinity (no upper limit). Higher the score, higher the level of insulin resistance. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
| Change in Glycated Haemoglobin (HbA1c) | Baseline (week 0); week 26 | Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
| Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | Baseline (week 0); week 26 | Change in IGF-I SDS from baseline (week 0) to week 26 is presented. IGF-I SDS was provided by the central laboratory; its calculation is based on the actual value of IGF-1 minus mean reference value of IGF-1 divided by reference standard deviation of IGF-1. The range for IGF-I SDS was from -10 to +10. Negative scores indicated a IGF-I below the mean IGF-I for a child with the same age and gender, whereas positive scores indicated a IGF-I above the mean IGF-I for a child with the same age and gender. Positive value in change from baseline in IGF-I SDS indicated that IGF-I SDS was higher than baseline IGF-I SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
| Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | Baseline (week 0); week 26 | Change in IGFBP-3 SDS from baseline (week 0) to week 26 is presented. The range for IGFBP-3 SDS was from -10 to +10. Negative scores indicated a IGFBP-3 below the mean IGFBP-3 for a child with the same age and gender, whereas positive scores indicated a IGFBP-3 above the mean IGFBP-3 for a child with the same age and gender. Positive value in change from baseline in IGFBP-3 SDS indicated that IGFBP-3 SDS was higher than baseline IGFBP-3 SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first. |
Countries
Algeria, Austria, Canada, Denmark, Estonia, France, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Norway, Poland, Russia, Serbia, Spain, Switzerland, Thailand, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Reporting Anchor and Disclosure 1452
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 38 sites in 12 countries as follows (number of sites that screened participants/ number of sites that randomized participants): Austria (2/1), France (2/2), Hungary (1/1), India (3/3), Israel (1/1), Italy (2/2), Japan (10/10), Latvia (1/1), Russia (6/6), Thailand (2/1), Ukraine (2/2) and United States (6/5).
Pre-assignment details
Participants were randomized (1:1:1:1:1 ratio) to receive either once-weekly Somapacitan or daily Norditropin treatment during the main phase (26-week) and extension phase I (26-week). Followed by 208-week additional long-term safety extension phase (extension II) and a 30-day follow-up period. Results in this summary are reported based on main phase and extension phase I. The extension phase II is still ongoing and results will be posted after one year of study completion date.
Participants by arm
| Arm | Count |
|---|---|
| Norditropin 0.035 mg/kg/Day Participants received 0.035 mg/kg/day subcutaneous injection of norditropin daily during the main phase (26-week) and extension phase I (26-week). | 12 |
| Norditropin 0.067 mg/kg/Day Participants received 0.067 mg/kg/day subcutaneous injection of norditropin daily during the main phase (26-week) and extension phase I (26-week). | 13 |
| Somapacitan 0.16 mg/kg/Week Participants received 0.16 mg/kg/week subcutaneous injection of somapacitan once weekly during the main phase (26-week) and extension phase I (26-week). | 12 |
| Somapacitan 0.20 mg/kg/Week Participants received 0.20 mg/kg/week subcutaneous injection of somapacitan once weekly during the main phase (26-week) and extension phase I (26-week). | 13 |
| Somapacitan 0.24 mg/kg/Week Participants received 0.24 mg/kg/week subcutaneous injection of somapacitan once weekly during the main phase (26-week) and extension phase I (26-week). | 12 |
| Total | 62 |
Baseline characteristics
| Characteristic | Norditropin 0.035 mg/kg/Day | Total | Somapacitan 0.24 mg/kg/Week | Somapacitan 0.20 mg/kg/Week | Somapacitan 0.16 mg/kg/Week | Norditropin 0.067 mg/kg/Day |
|---|---|---|---|---|---|---|
| Age, Continuous | 6.29 years STANDARD_DEVIATION 2.84 | 6.10 years STANDARD_DEVIATION 2.39 | 6.00 years STANDARD_DEVIATION 2.46 | 6.17 years STANDARD_DEVIATION 2.21 | 6.13 years STANDARD_DEVIATION 2.41 | 5.92 years STANDARD_DEVIATION 2.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 54 Participants | 11 Participants | 12 Participants | 8 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 24 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 34 Participants | 6 Participants | 7 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 6 Participants | 22 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 40 Participants | 8 Participants | 9 Participants | 8 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 7 / 12 | 6 / 13 | 7 / 12 | 9 / 13 | 8 / 12 |
| serious Total, serious adverse events | 1 / 12 | 0 / 13 | 0 / 12 | 1 / 13 | 0 / 12 |
Outcome results
Primary
Height Velocity
Height velocity (HV) was derived from height measurements taken at baseline (week 0) and week 26 visit as: HV = (height at 26 weeks visit - height at baseline)/(time from baseline to 26 weeks visit in years). The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first.
Time frame: Baseline (week 0); week 26
Population: Full analysis set (FAS) included all randomized participants exposed to the trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Height Velocity | 10.5 centimeter per year (cm/year) | Standard Deviation 2 |
| Norditropin 0.067 mg/kg/Day | Height Velocity | 11.9 centimeter per year (cm/year) | Standard Deviation 2.4 |
| Somapacitan 0.16 mg/kg/Week | Height Velocity | 8.9 centimeter per year (cm/year) | Standard Deviation 1.8 |
| Somapacitan 0.20 mg/kg/Week | Height Velocity | 11.1 centimeter per year (cm/year) | Standard Deviation 2.6 |
| Somapacitan 0.24 mg/kg/Week | Height Velocity | 11.2 centimeter per year (cm/year) | Standard Deviation 3.4 |
95% CI: [-3.2, 0.4]
95% CI: [-1.1, 2.5]
95% CI: [-2.6, 0.9]
95% CI: [-2.4, 1.2]
Secondary
Change in Fasting Plasma Glucose
Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: Safety analysis set (SAS) included all randomized participants exposed to trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Fasting Plasma Glucose | 0.382 millimoles per liter (mmol/L) | Standard Deviation 0.5 |
| Norditropin 0.067 mg/kg/Day | Change in Fasting Plasma Glucose | 0.192 millimoles per liter (mmol/L) | Standard Deviation 0.415 |
| Somapacitan 0.16 mg/kg/Week | Change in Fasting Plasma Glucose | 0.167 millimoles per liter (mmol/L) | Standard Deviation 0.485 |
| Somapacitan 0.20 mg/kg/Week | Change in Fasting Plasma Glucose | 0.200 millimoles per liter (mmol/L) | Standard Deviation 0.912 |
| Somapacitan 0.24 mg/kg/Week | Change in Fasting Plasma Glucose | 0.275 millimoles per liter (mmol/L) | Standard Deviation 0.693 |
Secondary
Change in Glycated Haemoglobin (HbA1c)
Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: SAS included all randomized participants exposed to trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Glycated Haemoglobin (HbA1c) | -0.10 Percentage of HbA1c | Standard Deviation 0.39 |
| Norditropin 0.067 mg/kg/Day | Change in Glycated Haemoglobin (HbA1c) | 0.03 Percentage of HbA1c | Standard Deviation 0.2 |
| Somapacitan 0.16 mg/kg/Week | Change in Glycated Haemoglobin (HbA1c) | 0.07 Percentage of HbA1c | Standard Deviation 0.15 |
| Somapacitan 0.20 mg/kg/Week | Change in Glycated Haemoglobin (HbA1c) | 0.12 Percentage of HbA1c | Standard Deviation 0.25 |
| Somapacitan 0.24 mg/kg/Week | Change in Glycated Haemoglobin (HbA1c) | 0.05 Percentage of HbA1c | Standard Deviation 0.24 |
Secondary
Change in Height Standard Deviation Score (HSDS)
Change in HSDS from baseline (week 0) to week 26 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. HSDS = \[(height/population median)\^skewness - 1\]/(skewness \* population standard deviation) where skewness, median and standard deviation is given by a reference growth table for the corresponding chronological age. The range for HSDS was -10 to +10. Negative scores indicated a height below the mean height for a child with the same age and gender, whereas positive scores indicated a height above the mean height for a child with the same age and gender. Positive value in change from baseline in HSDS indicated that HSDS was better than baseline HSDS In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first.
Time frame: Baseline (week 0); week 26
Population: FAS included all randomized participants exposed to the trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Height Standard Deviation Score (HSDS) | 0.61 score on a scale | Standard Deviation 0.19 |
| Norditropin 0.067 mg/kg/Day | Change in Height Standard Deviation Score (HSDS) | 0.73 score on a scale | Standard Deviation 0.3 |
| Somapacitan 0.16 mg/kg/Week | Change in Height Standard Deviation Score (HSDS) | 0.41 score on a scale | Standard Deviation 0.2 |
| Somapacitan 0.20 mg/kg/Week | Change in Height Standard Deviation Score (HSDS) | 0.66 score on a scale | Standard Deviation 0.29 |
| Somapacitan 0.24 mg/kg/Week | Change in Height Standard Deviation Score (HSDS) | 0.66 score on a scale | Standard Deviation 0.37 |
Secondary
Change in Height Velocity Standard Deviation Score (HVSDS)
Change in HVSDS from baseline (week 0) to week 26 is presented. HVSDS was derived using Prader standards. HV SDS was calculated using the formula: HV SDS = (height velocity - mean)/standard deviation (SD), where height velocity was the height velocity variable measured, mean and SD of height velocity by gender and age for the reference population. The range for HVSDS was -10 to +10. Negative scores indicated a height velocity below the mean height velocity for a child with the same age and gender, whereas positive scores indicated a height velocity above the mean height velocity for a child with the same age and gender. Positive value in change from baseline in HVSDS indicated that HVSDS was better than baseline HVSDS. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first.
Time frame: Baseline (week 0); week 26
Population: FAS included all randomized participants exposed to the trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Height Velocity Standard Deviation Score (HVSDS) | 6.37 score on a scale | Standard Deviation 3.05 |
| Norditropin 0.067 mg/kg/Day | Change in Height Velocity Standard Deviation Score (HVSDS) | 7.86 score on a scale | Standard Deviation 1.88 |
| Somapacitan 0.16 mg/kg/Week | Change in Height Velocity Standard Deviation Score (HVSDS) | 4.03 score on a scale | Standard Deviation 2.68 |
| Somapacitan 0.20 mg/kg/Week | Change in Height Velocity Standard Deviation Score (HVSDS) | 6.77 score on a scale | Standard Deviation 3.35 |
| Somapacitan 0.24 mg/kg/Week | Change in Height Velocity Standard Deviation Score (HVSDS) | 7.24 score on a scale | Standard Deviation 3.8 |
Secondary
Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Change in HOMA-IR from baseline (week 0) to week 26 is presented. Insulin resistance is a condition in which cells fail to respond to normal actions of hormone in body. HOMA-IR is calculated using a participant's fasting plasma insulin and glucose levels. HOMA-IR = fasting serum insulin (micro international units per milliliter (μU/ml)) × fasting plasma glucose (millimoles per liter (mmol/l)) / 22.5. HOMA-IR scores are classified as follows: less than 1.0: considered insulin sensitive, 0.5-1.4: considered healthy, above 1.8: considered early insulin resistance; above 2.7 is considered significant insulin resistance. HOMA-IR score ranges from 0-infinity (no upper limit). Higher the score, higher the level of insulin resistance. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: SAS included all randomized participants exposed to trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 0.85 HOMA-IR index | Standard Deviation 0.82 |
| Norditropin 0.067 mg/kg/Day | Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 1.17 HOMA-IR index | Standard Deviation 0.88 |
| Somapacitan 0.16 mg/kg/Week | Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 0.40 HOMA-IR index | Standard Deviation 0.48 |
| Somapacitan 0.20 mg/kg/Week | Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 0.57 HOMA-IR index | Standard Deviation 3.07 |
| Somapacitan 0.24 mg/kg/Week | Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 1.50 HOMA-IR index | Standard Deviation 2.1 |
Secondary
Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B)
Change in HOMA-B from baseline (week 0) to week 26 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin (picomoles per liter \[pmol/L\]) \* 1/6(microunit per milliliter \[µU/mL\]))/ FPG(mmol/L)-3.5). HOMA-beta score ranges from minus infinity to infinity (no limits). Higher score means better beta-cell function for HOMA-beta. Negative change from baseline (week 0) in HOMA-B indicated a worse outcome. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: SAS included all randomized participants exposed to trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | 6.12 HOMA-B index | Standard Deviation 99.55 |
| Norditropin 0.067 mg/kg/Day | Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | 63.35 HOMA-B index | Standard Deviation 46.01 |
| Somapacitan 0.16 mg/kg/Week | Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | 24.53 HOMA-B index | Standard Deviation 49.59 |
| Somapacitan 0.20 mg/kg/Week | Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | 0.75 HOMA-B index | Standard Deviation 65.08 |
| Somapacitan 0.24 mg/kg/Week | Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B) | 51.83 HOMA-B index | Standard Deviation 88.89 |
Secondary
Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS
Change in IGFBP-3 SDS from baseline (week 0) to week 26 is presented. The range for IGFBP-3 SDS was from -10 to +10. Negative scores indicated a IGFBP-3 below the mean IGFBP-3 for a child with the same age and gender, whereas positive scores indicated a IGFBP-3 above the mean IGFBP-3 for a child with the same age and gender. Positive value in change from baseline in IGFBP-3 SDS indicated that IGFBP-3 SDS was higher than baseline IGFBP-3 SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: FAS included all randomized participants exposed to the trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | 0.81 score on a scale | Standard Deviation 0.64 |
| Norditropin 0.067 mg/kg/Day | Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | 1.06 score on a scale | Standard Deviation 0.66 |
| Somapacitan 0.16 mg/kg/Week | Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | 0.77 score on a scale | Standard Deviation 0.68 |
| Somapacitan 0.20 mg/kg/Week | Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | 1.01 score on a scale | Standard Deviation 0.8 |
| Somapacitan 0.24 mg/kg/Week | Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS | 1.40 score on a scale | Standard Deviation 0.88 |
Secondary
Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS)
Change in IGF-I SDS from baseline (week 0) to week 26 is presented. IGF-I SDS was provided by the central laboratory; its calculation is based on the actual value of IGF-1 minus mean reference value of IGF-1 divided by reference standard deviation of IGF-1. The range for IGF-I SDS was from -10 to +10. Negative scores indicated a IGF-I below the mean IGF-I for a child with the same age and gender, whereas positive scores indicated a IGF-I above the mean IGF-I for a child with the same age and gender. Positive value in change from baseline in IGF-I SDS indicated that IGF-I SDS was higher than baseline IGF-I SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.
Time frame: Baseline (week 0); week 26
Population: FAS included all randomized participants exposed to the trial product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | 1.59 score on a scale | Standard Deviation 0.67 |
| Norditropin 0.067 mg/kg/Day | Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | 2.13 score on a scale | Standard Deviation 1.07 |
| Somapacitan 0.16 mg/kg/Week | Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | 1.48 score on a scale | Standard Deviation 0.9 |
| Somapacitan 0.20 mg/kg/Week | Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | 1.93 score on a scale | Standard Deviation 1.07 |
| Somapacitan 0.24 mg/kg/Week | Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) | 3.03 score on a scale | Standard Deviation 1.42 |
Secondary
Change in Ratio of Bone Age Versus Chronological Age
Change in ratio of bone age (years) versus chronological age (years) from baseline (week 0) to week 52 is presented. X-rays of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. X-ray images were sent to a central imaging laboratory for evaluation. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 52 or last trial contact, whichever came first.
Time frame: Baseline (week 0); week 52
Population: Safety anslyis set (SAS) included all randomized participants exposed to the trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Norditropin 0.035 mg/kg/Day | Change in Ratio of Bone Age Versus Chronological Age | -0.02 ratio (bone age/chronological age) | Standard Deviation 0.13 |
| Norditropin 0.067 mg/kg/Day | Change in Ratio of Bone Age Versus Chronological Age | 0.07 ratio (bone age/chronological age) | Standard Deviation 0.16 |
| Somapacitan 0.16 mg/kg/Week | Change in Ratio of Bone Age Versus Chronological Age | 0.07 ratio (bone age/chronological age) | Standard Deviation 0.08 |
| Somapacitan 0.20 mg/kg/Week | Change in Ratio of Bone Age Versus Chronological Age | 0.03 ratio (bone age/chronological age) | Standard Deviation 0.12 |
| Somapacitan 0.24 mg/kg/Week | Change in Ratio of Bone Age Versus Chronological Age | -0.00 ratio (bone age/chronological age) | Standard Deviation 0.1 |