Clinical Trial Results:
heiGHt: A multicenter, Phase 3, randomized, open-label, active-controlled, parallel-group trial investigating the safety, tolerability, and efficacy of lonapegsomatropin administered once a week versus standard daily hGH replacement therapy over 52 weeks in prepubertal children with growth hormone deficiency (GHD)
Summary
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EudraCT number |
2016-001145-11 |
Trial protocol |
DE IT BG PL GR |
Global end of trial date |
17 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Sep 2020
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First version publication date |
02 Sep 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TransCon hGH CT-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02781727 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ascendis Pharma A/S
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Sponsor organisation address |
Tuborg Boulevard 12, Hellerup, Denmark, 2900
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Public contact |
Clinical Trial Information Desk, Ascendis Pharma A/S, +45 70 22 22 44, clinhelpdesk@ascendispharma.com
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Scientific contact |
Clinical Trial Information Desk, Ascendis Pharma A/S, +45 70 22 22 44, clinhelpdesk@ascendispharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002692-PIP01-19 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Jan 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Jan 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate and compare the annualized height velocity of prepubertal children with growth failure due to GHD treated with weekly lonapegsomatropin to that of a commercially available daily hGH formulation at 52 weeks.
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Protection of trial subjects |
Institutional review board and independent ethics committee approval as well as signed informed consent from subjects was obtained prior to any trial-specific procedures.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Nov 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
Bulgaria: 3
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Country: Number of subjects enrolled |
Greece: 3
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Armenia: 10
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Country: Number of subjects enrolled |
Georgia: 11
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Country: Number of subjects enrolled |
Belarus: 5
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Country: Number of subjects enrolled |
Ukraine: 12
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Country: Number of subjects enrolled |
Turkey: 4
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Country: Number of subjects enrolled |
Romania: 3
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Country: Number of subjects enrolled |
Russian Federation: 50
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Country: Number of subjects enrolled |
New Zealand: 6
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Country: Number of subjects enrolled |
Australia: 2
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Country: Number of subjects enrolled |
United States: 42
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Worldwide total number of subjects |
162
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
133
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Adolescents (12-17 years) |
29
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
54 sites in 14 countries enrolled subjects (Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey, Ukraine, and United States). Subject screening was initiated in November 2016 and the final subject visit was in January 2019. | ||||||||||||||||||
Pre-assignment
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Screening details |
Screening lasted up to 6 weeks, plus a recommended period of up to 2 weeks between randomization and Visit 1. | ||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
162 | ||||||||||||||||||
Number of subjects completed |
161 | ||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 1 | ||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Lonapegsomatropin, 0.24 mg hGH/kg/wk | ||||||||||||||||||
Arm description |
Once weekly subcutaneous injection of lonapegsomatropin equivalent to 0.24 mg hGH/kg/wk for 52 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Lonapegsomatropn
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Investigational medicinal product code |
ACP-011
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Other name |
TransCon hGH
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Lonapegsomatropin was provided as a lyophilized powder, in single-use glass vials, reconstituted with 1 mL sterile water for injection, and administered via syringe and needle as a once-weekly subcutaneous injection of 0.24 mg hGH/kg/week.
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Arm title
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Genotropin, 0.24 mg hGH/kg/wk | ||||||||||||||||||
Arm description |
Once daily subcutaneous injection of human Growth Hormone (Genotropin) equivalent to 0.24 mg hGH/kg/week for 52 weeks. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Genotropin
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Investigational medicinal product code |
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Other name |
Human growth hormone, somatropin
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Pharmaceutical forms |
Powder and solvent for solution for injection in cartridge
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Genotropin was administered as a daily subcutaneous injection in a standard dose of 0.24 mg hGH/kg/week. The total weekly dose was equally split into 7 daily doses of 0.034 mg hGH/kg/day. A commercially-approved injection device was used for administration of the trial drug.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: A total of 162 subjects were randomized to the study drug in a 2:1 manner. Among randomized subjects, 161 were dosed with a study drug and 1 subject withdrew consent and did not receive a study drug. 105 subjects received lonapegsomatropin and 56 subjects received Genotropin. Nearly all randomized and dosed subjects completed the trial (159/161). |
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Baseline characteristics reporting groups
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Reporting group title |
Lonapegsomatropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once weekly subcutaneous injection of lonapegsomatropin equivalent to 0.24 mg hGH/kg/wk for 52 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Genotropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once daily subcutaneous injection of human Growth Hormone (Genotropin) equivalent to 0.24 mg hGH/kg/week for 52 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lonapegsomatropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once weekly subcutaneous injection of lonapegsomatropin equivalent to 0.24 mg hGH/kg/wk for 52 weeks. | ||
Reporting group title |
Genotropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once daily subcutaneous injection of human Growth Hormone (Genotropin) equivalent to 0.24 mg hGH/kg/week for 52 weeks. |
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End point title |
AHV at 52 weeks for weekly lonapegsomatropin and daily hGH treatment groups | ||||||||||||
End point description |
Annualized height velocity (AHV) in cm/year at week 52.
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End point type |
Primary
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End point timeframe |
52 weeks
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Statistical analysis title |
Analysis of Covariance (ANCOVA) Model | ||||||||||||
Statistical analysis description |
ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted.
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Comparison groups |
Lonapegsomatropin, 0.24 mg hGH/kg/wk v Genotropin, 0.24 mg hGH/kg/wk
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Number of subjects included in analysis |
161
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
= 0.0088 [2] | ||||||||||||
Method |
ANCOVA with multiple imputation | ||||||||||||
Confidence interval |
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Notes [1] - Non-inferiority margin of 2 cm/year [2] - two-sided |
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End point title |
AHV for the lonapegsomatropin and the daily hGH treatment groups over 52 weeks | |||||||||||||||||||||||||||
End point description |
Annualized height velocity (AHV) in cm/year by visit over 52 weeks.
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End point type |
Secondary
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End point timeframe |
At Week 5, Week 13, Week 26, Week 39, and Week 52.
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Statistical analysis title |
ANCOVA model | |||||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted.
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Comparison groups |
Lonapegsomatropin, 0.24 mg hGH/kg/wk v Genotropin, 0.24 mg hGH/kg/wk
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Number of subjects included in analysis |
161
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||
P-value |
= 0.0088 [3] | |||||||||||||||||||||||||||
Method |
ANCOVA with multiple imputation | |||||||||||||||||||||||||||
Confidence interval |
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Notes [3] - Week 5, P = 0.6402 Week 13, P = 0.1286 Week 26, P = 0.0017 Week 39, P = 0.0061 Week 52, P =0.0088 (two-sided) |
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End point title |
Change from baseline in Height SDS over 52 weeks for the lonapegsomatropin and the daily hGH treatment groups | |||||||||||||||||||||||||||
End point description |
Change from baseline in height (HT) standard deviation score by visit over 52 weeks.
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End point type |
Secondary
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End point timeframe |
At Week 5, Week 13, Week 26, Week 39, and Week 52.
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Statistical analysis title |
ANCOVA model | |||||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, as well as treatment and gender as factors.
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Comparison groups |
Genotropin, 0.24 mg hGH/kg/wk v Lonapegsomatropin, 0.24 mg hGH/kg/wk
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Number of subjects included in analysis |
161
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Analysis specification |
Post-hoc
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Analysis type |
superiority | |||||||||||||||||||||||||||
P-value |
= 0.0149 [4] | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Confidence interval |
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Notes [4] - Week 5, P = 0.7795 Week 13, P = 0.1078 Week 26, P = 0.0085 Week 39, P = 0.0130 Week 52, P = 0.0149 (two-sided) |
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End point title |
Average IGF-1 SDS by visit | ||||||||||||||||||||||||
End point description |
Average IGF-1 standard deviation score by visit over 52 weeks.
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End point type |
Secondary
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End point timeframe |
At Week 13, Week 26, Week 39, and Week 52.
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Statistical analysis title |
ANCOVA model | ||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test, baseline IGF-1 SDS as covariates, treatment and gender as factors. Modeled values begin at Week 13 corresponding with achievement of IGF-1 steady state. Average IGF-1 SDS values by visit for the Lonapegsomatropin group were derived from a population PD model; the average IGF-1 SDS values for the Genotropin group are represented by observed values.
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Comparison groups |
Lonapegsomatropin, 0.24 mg hGH/kg/wk v Genotropin, 0.24 mg hGH/kg/wk
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Number of subjects included in analysis |
161
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.0001 [5] | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Confidence interval |
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Notes [5] - P <0.0001 at Weeks 13, 26, 39, and 52 (two-sided) |
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End point title |
IGFBP-3 SDS by visit | |||||||||||||||||||||||||||
End point description |
IGFBP-3 standard deviation score by visit over 52 weeks.
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End point type |
Secondary
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End point timeframe |
At Week 5, Week, 13, Week 26, Week 39, and Week 52.
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Statistical analysis title |
Mixed Model for Repeated Measurement (MMRM) model | |||||||||||||||||||||||||||
Statistical analysis description |
MMRM model includes baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline IGFBP-3 SDS as covariates, treatment, visit, treatment by visit interaction, and gender as fixed factors, and subject as random effect.
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Comparison groups |
Lonapegsomatropin, 0.24 mg hGH/kg/wk v Genotropin, 0.24 mg hGH/kg/wk
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Number of subjects included in analysis |
161
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||
P-value |
= 0.0454 [6] | |||||||||||||||||||||||||||
Method |
MMRM | |||||||||||||||||||||||||||
Confidence interval |
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Notes [6] - Week 5, P = 0.0134 Week 13, P < 0.0001 Week 26, P < 0.0001 Week 39, P < 0.0001 Week 52, P = 0.0454 (two-sided) |
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End point title |
Incidence of treatment emergent anti-hGH binding antibody formation | |||||||||
End point description |
Incidence of treatment emergent anti-hGH binding antibody formation during the 52 week study. All samples were negative for anti-hGH neutralizing antibodies.
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End point type |
Secondary
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End point timeframe |
Start of study treatment through Week 52.
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From the first trial-related activity after the subject signed the informed consent until the end of the post-treatment follow-up period (up to week 52).
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Adverse event reporting additional description |
An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
Lonapegsomatropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once weekly subcutaneous injection of lonapegsomatropin equivalent to 0.24 mg hGH/kg/wk for 52 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Genotropin, 0.24 mg hGH/kg/wk
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Reporting group description |
Once daily subcutaneous injection of human Growth Hormone (Genotropin) equivalent to 0.24 mg hGH/kg/week for 52 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Sep 2017 |
The amendment to the original protocol was issued to incorporate feedback from international regulatory agencies and to add pertinent clarifications and administrative edits. The amendment maintained the original intent of the protocol and aligned where possible, with current standard medical practice across various regions globally. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |