Trial Outcomes & Findings for Long-Acting Growth Hormone in Children Compared to Daily rhGH (NCT NCT02339090)
NCT ID: NCT02339090
Last Updated: 2022-12-30
Results Overview
Height measured without shoes in triplicate by stadiometer. Annual height velocity was calculated as (height at Month 12 - height at Baseline)/(Month 12 Date - Baseline Date) \* 365.25, where height was expressed as centimeters (cm) so that height velocity is expressed as centimeters per year (cm/yr). Annual height velocity after 12 months continuous treatment with either somavaratan or daily rhGH has been reported. Missing data was imputed using last observation carried forward. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model.
COMPLETED
PHASE3
138 participants
12 months
2022-12-30
Participant Flow
Participants were stratified by region (North America and Europe), age (above and below anticipated median age of 7.5 years) and baseline Insulin-like growth factor-I (IGF-I) standard deviation score (SDS) (above and below anticipated median of -1.7) and randomized in a 3:1 ratio to receive either somavaratan or recombinant human growth hormone (rhGH).
Participant milestones
| Measure |
Somavaratan
Participants received somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months.
|
rhGH
Participants received commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Overall Study
STARTED
|
104
|
34
|
|
Overall Study
Received a Least 1 Dose of Study Drug
|
104
|
32
|
|
Overall Study
COMPLETED
|
98
|
29
|
|
Overall Study
NOT COMPLETED
|
6
|
5
|
Reasons for withdrawal
| Measure |
Somavaratan
Participants received somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months.
|
rhGH
Participants received commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Non-compliance With Study Drug
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Poor Growth
|
3
|
0
|
|
Overall Study
Randomized but not treated
|
0
|
2
|
Baseline Characteristics
Long-Acting Growth Hormone in Children Compared to Daily rhGH
Baseline characteristics by cohort
| Measure |
Somavaratan
n=104 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=32 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
Total
n=136 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
7.0 years
STANDARD_DEVIATION 2.03 • n=5 Participants
|
6.9 years
STANDARD_DEVIATION 2.38 • n=7 Participants
|
7.0 years
STANDARD_DEVIATION 2.11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
96 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
125 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
91 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
122 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: ITT population included all randomized participants.
Height measured without shoes in triplicate by stadiometer. Annual height velocity was calculated as (height at Month 12 - height at Baseline)/(Month 12 Date - Baseline Date) \* 365.25, where height was expressed as centimeters (cm) so that height velocity is expressed as centimeters per year (cm/yr). Annual height velocity after 12 months continuous treatment with either somavaratan or daily rhGH has been reported. Missing data was imputed using last observation carried forward. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model.
Outcome measures
| Measure |
Somavaratan
n=104 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=34 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Annual Height Velocity
|
9.43 cm/year
Standard Error 0.28
|
10.70 cm/year
Standard Error 0.48
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Height SDS was determined using the Center for Disease Control (CDC) Clinical Growth Charts; 2000. The SD score was calculated as the participant's height value minus the mean divided by the standard deviation (SD). The mean and the SD vary depending on the age and sex of the participant. Mean change from baseline in height SDS at Month 12 is presented.
Outcome measures
| Measure |
Somavaratan
n=98 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=30 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Height Standard Deviation Score (SDS) at Month 12
|
0.8 SD score
Standard Deviation 0.53
|
1.0 SD score
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Bone age was assessed from a radiograph of the left hand and wrist by central reader.
Outcome measures
| Measure |
Somavaratan
n=98 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=29 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader
|
1.1 months
Standard Deviation 0.47
|
1.3 months
Standard Deviation 0.55
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The BMI is a person's weight in kilograms (kg) divided by the square of height in meters.
Outcome measures
| Measure |
Somavaratan
n=99 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=30 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Body Mass Index (BMI) at Month 12
|
1.1 kg/m^2
Standard Deviation 0.86
|
-0.1 kg/m^2
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Body weight measured in light clothing and without shoes.
Outcome measures
| Measure |
Somavaratan
n=100 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=30 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Body Weight at Month 12
|
4.9 kg
Standard Deviation 1.87
|
3.8 kg
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The SD score was calculated as the actual value of IGF-I minus mean reference value of IGF-1 divided by reference standard deviation of IGF-I. The mean and the SD vary depending on the age and sex of the participant. Change in IGF-I level (SD score) at Month 12 from Baseline was assessed. A higher score reflects a better outcome.
Outcome measures
| Measure |
Somavaratan
n=98 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=28 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12
|
0.9 SD score
Standard Deviation 0.99
|
1.8 SD score
Standard Deviation 0.72
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Outcome measures
| Measure |
Somavaratan
n=90 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=26 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12
|
32.2 nanomoles (nmol)/milliliter (mL)
Standard Deviation 30.2
|
49.8 nanomoles (nmol)/milliliter (mL)
Standard Deviation 19.1
|
SECONDARY outcome
Timeframe: Baseline up to Month 12Population: Safety population included all participants who received any amount of study drug.
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Outcome measures
| Measure |
Somavaratan
n=104 Participants
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=32 Participants
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
80 Participants
|
22 Participants
|
Adverse Events
Somavaratan
rhGH
Serious adverse events
| Measure |
Somavaratan
n=104 participants at risk
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=32 participants at risk
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Congenital, familial and genetic disorders
Arnold-Chiari malformation
|
1.9%
2/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.96%
1/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Infections and infestations
Otitis media
|
0.96%
1/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Nervous system disorders
Syringomyelia
|
0.96%
1/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Renal and urinary disorders
Glomerulonephritis
|
0.96%
1/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
Other adverse events
| Measure |
Somavaratan
n=104 participants at risk
Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.
|
rhGH
n=32 participants at risk
Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.
|
|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
11.5%
12/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
9.4%
3/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
7/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
6.2%
2/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Infections and infestations
Otitis media
|
6.7%
7/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Infections and infestations
Ear infection
|
5.8%
6/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
0.00%
0/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
General disorders
Pyrexia
|
17.3%
18/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
12.5%
4/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
General disorders
Injection site pain
|
17.3%
18/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
9.4%
3/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
General disorders
Injection site haematoma
|
5.8%
6/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
3.1%
1/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.4%
15/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
6.2%
2/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.7%
7/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
3.1%
1/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.9%
2/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
6.2%
2/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
11.5%
12/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
15.6%
5/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
7/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
3.1%
1/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Gastrointestinal disorders
Nausea
|
4.8%
5/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
9.4%
3/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.6%
11/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
9.4%
3/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.5%
12/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
3.1%
1/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Nervous system disorders
Headache
|
15.4%
16/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
12.5%
4/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
|
Endocrine disorders
Hypothyroidism
|
1.9%
2/104 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
6.2%
2/32 • Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee US Sites: Institution shall cause Principal Investigator to submit a complete copy of the proposed publication to Sponsor at least 60 days prior to presentation or submission to any third party. Non-US sites: The Investigator and the Institution agree that any proposed publication relating to the research and/or Study conducted under this Agreement will be submitted to Sponsor for review at least 90 days prior to submission for publication. Additional agreement conditions apply.
- Publication restrictions are in place
Restriction type: OTHER