Clinical Trial Results:
A Phase 3, Randomised, Multicenter, Open-Label, Crossover Study Assessing Subject Perception of Treatment Burden With Use of Weekly Growth Hormone (Somatrogon) Versus Daily Growth Hormone (Genotropin) Injections in Children With Growth Hormone Deficiency
Summary
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EudraCT number |
2018-000918-38 |
Trial protocol |
GB SK CZ BG |
Global end of trial date |
28 Aug 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Mar 2021
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First version publication date |
04 Mar 2021
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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 |
C0311002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03831880 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Dec 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Aug 2020
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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 the treatment burden of a weekly Somatrogon injection schedule and a daily Genotropin injection schedule.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Feb 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Bulgaria: 10
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Country: Number of subjects enrolled |
Czechia: 16
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Country: Number of subjects enrolled |
Slovakia: 5
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 52
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Worldwide total number of subjects |
87
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EEA total number of subjects |
31
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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) |
46
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Adolescents (12-17 years) |
41
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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 |
- | |||||||||||||||
Pre-assignment
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Screening details |
A total of 107 subjects were enrolled and 87 subjects aged 3 to less than (<) 18 years, with growth hormone deficiency (GHD) who were stable on treatment with daily Genotropin were randomised in this study. | |||||||||||||||
Period 1
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Period 1 title |
Baseline Period
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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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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Daily Genotropin Then Weekly Somatrogon | |||||||||||||||
Arm description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Genotropin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.
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Arm title
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Weekly Somatrogon Then Daily Genotropin | |||||||||||||||
Arm description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Somatrogon
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.
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Period 2
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Period 2 title |
Period 1 (12 Weeks)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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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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Daily Genotropin Then Weekly Somatrogon | |||||||||||||||
Arm description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Genotropin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.
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Arm title
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Weekly Somatrogon Then Daily Genotropin | |||||||||||||||
Arm description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Somatrogon
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.
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Period 3
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Period 3 title |
Period 2 (12 Weeks)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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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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Daily Genotropin Then Weekly Somatrogon | |||||||||||||||
Arm description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Genotropin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.
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Arm title
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Weekly Somatrogon Then Daily Genotropin | |||||||||||||||
Arm description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Somatrogon
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.
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Period 4
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Period 4 title |
Follow-up
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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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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Daily Genotropin Then Weekly Somatrogon | |||||||||||||||
Arm description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Weekly Somatrogon Then Daily Genotropin | |||||||||||||||
Arm description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Daily Genotropin Then Weekly Somatrogon
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Reporting group description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Weekly Somatrogon Then Daily Genotropin
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Reporting group description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Daily Genotropin Then Weekly Somatrogon
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Reporting group description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | ||
Reporting group title |
Weekly Somatrogon Then Daily Genotropin
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Reporting group description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | ||
Reporting group title |
Daily Genotropin Then Weekly Somatrogon
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Reporting group description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | ||
Reporting group title |
Weekly Somatrogon Then Daily Genotropin
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Reporting group description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | ||
Reporting group title |
Daily Genotropin Then Weekly Somatrogon
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Reporting group description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | ||
Reporting group title |
Weekly Somatrogon Then Daily Genotropin
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Reporting group description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | ||
Reporting group title |
Daily Genotropin Then Weekly Somatrogon
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Reporting group description |
Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug. | ||
Reporting group title |
Weekly Somatrogon Then Daily Genotropin
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Reporting group description |
Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug. | ||
Subject analysis set title |
Genotropin
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2).
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Subject analysis set title |
Somatrogon
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2).
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End point title |
Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire [1] | ||||||||||||
End point description |
Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire [2] | ||||||||||||
End point description |
Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Week 12
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire [3] | ||||||||||||
End point description |
Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Week 24
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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No statistical analyses for this end point |
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End point title |
Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 24
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Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
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Number of subjects included in analysis |
167
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [4] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-15.49
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-19.71 | ||||||||||||
upper limit |
-11.27 | ||||||||||||
Notes [4] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
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End point title |
Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the Injection Pen Assessment Questionnaire (IPAQ) patient-reported outcome (PRO) tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the IPAQ PRO tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0017 [5] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-5.39
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-8.69 | ||||||||||||
upper limit |
-2.09 | ||||||||||||
Notes [5] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [6] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-13.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19.74 | ||||||||||||
upper limit |
-7.45 | ||||||||||||
Notes [6] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [7] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-24.34
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-30.1 | ||||||||||||
upper limit |
-18.57 | ||||||||||||
Notes [7] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0739 [8] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-7.83
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-16.42 | ||||||||||||
upper limit |
0.77 | ||||||||||||
Notes [8] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [9] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-17.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-25.15 | ||||||||||||
upper limit |
-10.06 | ||||||||||||
Notes [9] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
123
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.6137 [10] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.71
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.09 | ||||||||||||
upper limit |
3.51 | ||||||||||||
Notes [10] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
34
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.8404 [11] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.56
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.29 | ||||||||||||
upper limit |
6.41 | ||||||||||||
Notes [11] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [12] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-13.47
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-17.59 | ||||||||||||
upper limit |
-9.35 | ||||||||||||
Notes [12] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire | |||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire | ||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0245 [13] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.76
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.16 | ||||||||||||
upper limit |
-0.36 | ||||||||||||
Notes [13] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||
End point title |
Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire | |||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “If you were given the choice between the daily growth hormone injection pen and the weekly growth hormone injection pen, which pen would you choose?” Response was: 1) the daily injection pen (Genotropin) or 2) the weekly injection pen (Somatrogon). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Week 24
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule do you prefer overall?” by choosing from any 1 option from: 1) prefer the daily injection schedule; 2) prefer the weekly injection schedule; 3) no preference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was more convenient overall?” by choosing from any 1 option from: 1) daily injection schedule was more convenient; 2) weekly injection schedule was more convenient; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was easier to follow overall?” by choosing from any 1 option from: 1) easier to follow daily injection schedule; 2) easier to follow weekly injection schedule; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which pen was easier to use?” from Section II of the IPAQ PRO tool. Question had 4 parts: preparing the injection pen (Part I), setting the dose (Part II), injecting the medicine (Part III) and storing the pen (Part IV). Subjects/caregiver expressed their preference by choosing from any 1 option for each activity from: 1) daily pen easier to use; 2) weekly pen easier to use; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to subject life interference. Subjects were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). The subjects expressed their preference by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Caregivers of subjects were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to caregiver life interference and were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to family life interference and assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire | ||||||||||||||||||||||||
End point description |
Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “How beneficial was to take injections less often?” from Section II of the IPAQ PRO tool pertaining to benefit relating to the Injection schedule and used a 5-point scale: 1= extremely beneficial, 2= very beneficial, 3= moderately beneficial, 4= slightly beneficial and 5= not at all beneficial. Lower score of benefit relating to injection schedule meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects/caregiver dyads were asked 4 questions “Which schedule would be better able to follow?” (Question 1), “Which schedule would be more likely to follow for a longer time?” (Question 2), “Which schedule would be better able to follow for a longer time?” (Question 3) and “Which schedule would be more likely to follow?” (Question 4) from Section II of the IPAQ PRO tool related to subject intention to comply with treatment. Options for each question were: 1) daily injection (Genotropin), 2) weekly injection (Somatrogon) or 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24 | |||||||||||||||||||||
End point description |
The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study | ||||||||||||
End point description |
The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Genotropin versus Somatrogon | ||||||||||||
Comparison groups |
Genotropin v Somatrogon
|
||||||||||||
Number of subjects included in analysis |
167
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [14] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-14.58
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18.72 | ||||||||||||
upper limit |
-10.44 | ||||||||||||
Notes [14] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects. |
|
||||||||||||||||||||||
End point title |
Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs | |||||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. Treatment-emergent AEs (TEAEs) were defined as events that occurred between first dose of study drug up to 35 days after last dose of study drug. Related TEAEs were those AEs who had relation to the study treatment and was judged by investigator. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
|
|||||||||||||||||||||
End point type |
Other pre-specified
|
|||||||||||||||||||||
End point timeframe |
Baseline up to 29 Weeks
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Subjects With Adverse Events per Severity | ||||||||||||||||||
End point description |
AE was assessed according to severity; mild (did not interfered with subject's usual function), moderate (interfered to some extent with subject's usual function) and severe (interfered significantly with subject's usual function). The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
|
||||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||||
End point timeframe |
Baseline up to 29 Weeks
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Subjects With Discontinuations due to Adverse Events (AEs) | |||||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. The discontinuations due to adverse events was defined for subjects. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
|
|||||||||
End point type |
Other pre-specified
|
|||||||||
End point timeframe |
Baseline up to 29 Weeks
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Subjects With Laboratory Abnormalities | |||||||||||||||
End point description |
The laboratory abnormality parameters included Hematology: erythrocyte (ery.) mean corpuscular volume, ery. mean corpuscular hemoglobin:<0.9*lower limit normal (LLN), leukocytes:<0.6*LLN, lymphocytes:<0.8*LLN, neutrophils:<0.8*LLN greater than (>) 1.2*upper limit normal (ULN), eosinophils, monocytes:>1.2*ULN. Clinical chemistry: bilirubin, direct bilirubin, indirect bilirubin:>1.5*ULN, gamma glutamyl transferase:>3.0*ULN, albumin:>1.2*ULN, blood urea nitrogen:>1.3*ULN, urate:>1.2*ULN, high-density lipoprotein (HDL) cholesterol:<0.8*LLN, potassium, magnesium:>1.1*ULN, phosphate:>1.2*ULN, bicarbonate:<0.9*LLN, creatine kinase:>2.0*ULN. Urinalysis: specific gravity:>1.030, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase:>=1. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects evaluable for specified time points.
|
|||||||||||||||
End point type |
Other pre-specified
|
|||||||||||||||
End point timeframe |
Week 1 to Week 12, Week 13 to Week 24
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Number of Subjects With Positive Anti-Recombinant Human Growth Hormone (rhGH) Antibodies and Neutralising Antibodies (NAb) | |||||||||||||||||||||||||||
End point description |
Blood samples were collected for determination of rhGH and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
|
|||||||||||||||||||||||||||
End point type |
Other pre-specified
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Number of Subjects With Positive Anti-Somatrogon Antibodies and Neutralising Antibodies (NAb) | |||||||||||||||||||||||||||
End point description |
Blood samples were collected for determination of anti-somatrogon antibodies and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here, “99999” signifies subjects were not tested for anti-somatrogon antibodies.
|
|||||||||||||||||||||||||||
End point type |
Other pre-specified
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12, Week 24
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to 35 days after last dose (up to 29 weeks)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Genotropin
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Reporting group description |
Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Somatrogon
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Reporting group description |
Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Jul 2018 |
(A) Schedule of Activities. Medication dispensation added for Genotropin at Visits 3 and 6.
(B) Schedule of Activities. DYAD Questionnaire (completed by Clinical Site Staff) added at Visits 1, 4 and 7.
(C) Section 4.1. Inclusion criterion #2 (Currently on treatment with either Genotropin Pen®, Genotropin GoQuick Pen®, HumatroPen® [United States of America {USA} only], or Omnitrope® Pen [USA only]) >=3 months and had been compliant on a stable dose (+/-10%) for at least 3 months prior to screening), was modified to allow for GHD subjects on a wider range of doses to enroll in the study.
(D) Section 4.2. Exclusion criterion #5 (Other causes of short stature such as uncontrolled primary hypothyroidism and rickets), was modified to remove celiac disease as exclusionary. As this is not an efficacy study assessing linear growth, children with celiac disease (which can impact growth) need not be excluded.
(E) Section 5. Clarification added regarding which body weight measurement is to be used for dosing of somatrogon at Visits 1 and 4.
(F) Sections 6.2.3 and 6.2.6. Genotropin drug dispensation added. |
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28 Aug 2018 |
(A) Schedule of Activities. Anti-rhGH antibodies (and neutralising antibodies) added at Screening, and Visits 4 and 7 at the request of the FDA.
(B) Section 2 and Protocol Summary. Detection of anti-rhGH antibodies (and neutralising antibodies) added to align with FDA request.
(C) Section 5.4. Arm included as an allowable injection site for Genotropin; its prior omission was in error. |
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08 Nov 2018 |
(A) Added free thyroxine (FT4) testing at Screening and at Visits 4 and 7 at the request of the MHRA.
(B) Modified Section 13, definition of end of trial to be last subject last visit (LSLV) at the request of the MHRA. |
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03 May 2019 |
(A) Section 4.2. Addition of children with closed epiphyses to the Exclusion Criteria to address the request of EU Health Authorities.
(B) Section 4.2. Exclusion criteria regarding allowable injectable medications clarified.
(C) Sections 5.5, 6.1.1, 6.2.3, & 6.2.4. Dosing windows expanded for Genotropin (36 hours +/- 24 hours) and somatrogon (7 days +/- 72 hours) prior to Visits 1 and 4 providing increased flexibility in dosing for subjects/caregivers prior to visits.
(D) Section 5.8.1. Allowable injectable concomitant medications clarified. |
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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 |