Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3 Multicenter, Open Label, Multi Cohort Study to Evaluate the Efficacy and Safety of Somatropin in Japanese Participants with Prader-Willi Syndrome (PWS).

    Summary
    EudraCT number
    		 2024-000101-32
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    15 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Oct 2024
    First version publication date
    20 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A6281323
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04697381
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of somatropin in participants with PWS.
    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 trials participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Feb 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 33
    Worldwide total number of subjects
    33
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    7
    Adolescents (12-17 years)
    5
    Adults (18-64 years)
    21
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants diagnosed with PWS received somatropin, a recombinant human growth hormone (r-hGH) in this study.

    Pre-assignment
    Screening details
    		 This study had 3 cohorts (GH naive pediatric cohort, GH treated pediatric cohort and adult cohort).

    Period 1
    Period 1 title
    Treatment Period (12 Months)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GH Naive Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.245 mg/kg/week was administered.

    Arm title
    		 GH Treated Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 milligram/day (mg/day). Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.084 mg/kg/week was administered.

    Arm title
    		 Adult Cohort
    Arm description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.042- 0.084 mg/kg/week was administered.

    Number of subjects in period 1
    		GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Started
    6
    7
    20
    Completed
    6
    7
    20
    Period 2
    Period 2 title
    Extension Period (36 Months)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GH Naive Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.245 mg/kg/week was administered.

    Arm title
    		 GH Treated Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants’ symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.084 mg/kg/week was administered.

    Arm title
    		 Adult Cohort
    Arm description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants’ symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.042- 0.084 mg/kg/week was administered.

    Number of subjects in period 2
    		GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Started
    6
    7
    20
    Completed
    6
    7
    14
    Not completed
    0
    0
    6
         Physician decision
    -
    -
    2
         Adverse events
    -
    -
    3
         Unspecified
    -
    -
    1
    Period 3
    Period 3 title
    Follow up period (28 days)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GH Naive Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.245 mg/kg/week was administered.

    Arm title
    		 GH Treated Pediatric Cohort
    Arm description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants’ symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.084 mg/kg/week was administered.

    Arm title
    		 Adult Cohort
    Arm description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants’ symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    PNU-180307
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Somatropin 0.042- 0.084 mg/kg/week was administered.

    Number of subjects in period 3
    		GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Started
    6
    7
    14
    Completed
    6
    7
    20
    Joined
    0
    0
    6
         Continue to follow up
    -
    -
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    GH Naive Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    GH Treated Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 milligram/day (mg/day). Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    Adult Cohort
    Reporting group description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort Total
    Number of subjects
    		 6 7 20 33
    Age Categorical
    Units: Participants
        Less than (<6) years
    		 3 0 0 3
        6-12 years
    		 3 1 0 4
        13-17 years
    		 0 5 0 5
        18-44 years
    		 0 1 20 21
        More than equal to (>=) 45 years
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 5.83 ( 2.79 ) 14.86 ( 2.67 ) 23.90 ( 5.39 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 2 3 13 18
        Male
    		 4 4 7 15
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0
        Not Hispanic or Latino
    		 6 7 20 33
        Unknown or Not Reported
    		 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 6 7 20 33
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 0 0 0 0
        White
    		 0 0 0 0
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    GH Naive Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    GH Treated Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 milligram/day (mg/day). Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    Adult Cohort
    Reporting group description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.
    Reporting group title
    GH Naive Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    GH Treated Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants’ symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    Adult Cohort
    Reporting group description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants’ symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.
    Reporting group title
    GH Naive Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 milligram per kilogram per week (mg/kg/week) subcutaneously. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    GH Treated Pediatric Cohort
    Reporting group description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants’ symptoms and serum insulin-like growth factor-1 (IGF-1) levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    Adult Cohort
    Reporting group description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants’ symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months. and Extension Period was of 36 months. Participants were followed up to 28 days.

    Primary: Change From Baseline to Month 12 in Lean Body Mass Measured by Dual-Energy X-ray Absorptiometry (DEXA): Adult Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Lean Body Mass Measured by Dual-Energy X-ray Absorptiometry (DEXA): Adult Cohort [1] [2]
    End point description
    Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass [kg] + fat mass [kg]) *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure this time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    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: The end point is reporting statistics for the arms specified
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 Adult Cohort
    Number of subjects analysed
    19
    Units: Percentage of body mass
        least squares mean (confidence interval 95%)
    3.09 (1.85 to 4.33)
    No statistical analyses for this end point

    Primary: Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort [3] [4]
    End point description
    Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass [kg] + fat mass [kg]) *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Primary
    End point timeframe
    Baseline, Month 12
    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
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort
    Number of subjects analysed
    6
    6
    Units: Percentage of body mass
        arithmetic mean (standard deviation)
    4.59 ( 4.490 )
    -1.34 ( 3.238 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 12 in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA)-Adult Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA)-Adult Cohort [5]
    End point description
    Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass [kg] + fat mass [kg]) *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 Adult Cohort
    Number of subjects analysed
    19
    Units: Percentage of body mass
        least squares mean (confidence interval 95%)
    2.03 (-0.67 to 4.73)
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort [6]
    End point description
    Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass [kg] + fat mass [kg]) *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort
    Number of subjects analysed
    6
    5
    Units: Percentage of body mass
        arithmetic mean (standard deviation)
    3.32 ( 3.867 )
    0.58 ( 4.711 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 12 in Body fat (Percentage) Measured by DEXA: Adult Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Body fat (Percentage) Measured by DEXA: Adult Cohort [7]
    End point description
    Body fat was assessed by DEXA scan and calculated as body fat (%) = body fat (kg) / [lean body mass (kg) + body fat (kg)] *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 Adult Cohort
    Number of subjects analysed
    19
    Units: Percentage of body fat
        least squares mean (confidence interval 95%)
    -3.09 (-4.33 to -1.85)
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 12 in Body fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Body fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort [8]
    End point description
    Body fat was assessed by DEXA scan and calculated as body fat (%) = body fat (kg) / [lean body mass (kg) + body fat (kg)] *100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort
    Number of subjects analysed
    6
    6
    Units: Percentage of body fat
        arithmetic mean (standard deviation)
    -4.59 ( 4.490 )
    1.34 ( 3.238 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. TEAEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. Full analysis set included all participants assigned to study intervention and who took at least one dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From dose 1 up to 28 days after end of study treatment (maximum duration up to 49 months)
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Number of subjects analysed
    6
    7
    20
    Units: Participants
        TEAEs
    5
    7
    19
        TESAEs
    0
    1
    3
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT)

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT)
    End point description
    Adipose tissue distribution was measured by abdominal CT. Areas of subcutaneous adipose tissue (SAT) (centimeter square [cm^2]), visceral adipose tissue (VAT) (cm^2) were measured at the level of the umbilicus by abdominal CT. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. "Number of Participants Analysed” signifies participants evaluable for this endpoint measure at this time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Number of subjects analysed
    6
    6
    19
    Units: Centimeter square (cm^2)
    arithmetic mean (standard deviation)
        Change at Month 12, SAT
    60.423 ( 138.2001 )
    102.222 ( 211.9111 )
    -13.764 ( 31.0212 )
        Change at Month 12, VAT
    4.825 ( 13.5401 )
    -13.403 ( 28.5490 )
    -4.040 ( 16.8243 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Month 6 in Lean Body Mass Measured by DEXA: Adult Cohort Only

    		 Close Top of page
    End point title
    		 Change From Baseline to Month 6 in Lean Body Mass Measured by DEXA: Adult Cohort Only [9]
    End point description
    Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass [kg] + fat mass [kg])*100. Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 Adult Cohort
    Number of subjects analysed
    20
    Units: Percentage of body mass
        least squares mean (confidence interval 95%)
    2.38 (1.30 to 3.46)
    No statistical analyses for this end point

    Secondary: Number of Participants With Laboratory Test Abnormalities

    		 Close Top of page
    End point title
    		 Number of Participants With Laboratory Test Abnormalities
    End point description
    Criteria for abnormal laboratory values for chemistry parameters: alanine aminotransferase, alkaline phosphatase greater than (>) 3.0*upper limit of normal (ULN), albumin > 1.2*ULN, urea nitrogen millimoles per liter (mmol/L) > 1.3*ULN, HDL cholesterol mmol/L less than (<) 0.8* lower limit of normal (LLN), LDL cholesterol mmol/L >1.2*ULN, triglycerides mmol/L > 1.3*ULN, thyrotropin milliunits per liter (mU/L) <0.8*LLN and >1.2*ULN, glucose (mmol/L) >1.5*ULN, hemoglobin A1C liter of cells per liter of blood (L/L) >1.3*ULN. FAS included all participants assigned to study intervention and who took at least one dose of study intervention.
    End point type
    Secondary
    End point timeframe
    49 months
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort Adult Cohort
    Number of subjects analysed
    6
    7
    20
    Units: Participants
    5
    3
    16
    No statistical analyses for this end point

    Secondary: Bone Maturation

    		 Close Top of page
    End point title
    		 Bone Maturation [10]
    End point description
    Bone maturation is the process whereby the tissue undergoes changes from the embryonic rudiment of bone to the adult form. Bone maturation was calculated as bone age divided by chronological age. Participants with bone maturation value greater than 1 is presented in this outcome measure. FAS included all participants assigned to study intervention and who took at least one dose of study intervention.
    End point type
    Secondary
    End point timeframe
    12 months
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified
    End point values
    		 GH Naive Pediatric Cohort GH Treated Pediatric Cohort
    Number of subjects analysed
    6
    7
    Units: Participants
    4
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From dose 1 up to 28 days after end of study treatment (maximum duration up to 49 months)
    Adverse event reporting additional description
    Same event may appear as both non-SAE & SAE. What is presented are distinct events. An event may be categorized as serious in 1 participant and non-SAE in other participant, or a participant may have experienced both SAE and non-SAE.FAS included all participants assigned to study intervention and who took at least one dose of study intervention.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v26.1
    Reporting groups
    Reporting group title
    GH naive pediatric cohort
    Reporting group description
    		 Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 mg/kg/week subcutaneously. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    Adult cohort
    Reporting group description
    		 Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Reporting group title
    GH treated pediatric cohort
    Reporting group description
    		 Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants symptoms and IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days.

    Serious adverse events
    		 GH naive pediatric cohort Adult cohort GH treated pediatric cohort
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 20 (15.00%)
    1 / 7 (14.29%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull fractured base
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Sinus node dysfunction
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Affect lability
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 GH naive pediatric cohort Adult cohort GH treated pediatric cohort
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 6 (83.33%)
    19 / 20 (95.00%)
    7 / 7 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    General disorders and administration site conditions
    Extravasation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    8
    1
    Malaise
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Injection site reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Testicular pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Genital tract inflammation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Snoring
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Cough variant asthma
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Psychiatric disorders
    Dissociative disorder
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Conversion disorder
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Dysphoria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Body height increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Glycosylated haemoglobin increased
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 20 (15.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    3
    0
    Insulin-like growth factor increased
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 20 (15.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    3
    2
    Liver function test increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Injury, poisoning and procedural complications
    Immunisation reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    1
    Chillblains
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    3
    0
    Contusion
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    5
    1
    Fall
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    7
    2
    Foot fracture
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Lip injury
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 20 (15.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    3
    1
    Arthropod bite
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    2
    1
    Subcutaneous haematoma
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Wound
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Procedural pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Dysaesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 20 (15.00%)
    1 / 7 (14.29%)
         occurrences all number
    5
    4
    1
    Loss of consciousness
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Ear pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    3
    1
    0
    Deafness unilateral
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Ear pruritus
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    3
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Glaucoma
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Eczema eyelids
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Dental caries
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Constipation
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 20 (15.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    3
    0
    Angular cheilitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Anal prolapse
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    1
    0
    Anal polyp
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Hypoaesthesia teeth
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Blister
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Eczema
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Haemorrhage subcutaneous
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    3
    0
    0
    Hand dermatitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Ingrowing nail
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Miliaria
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Urticaria
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    3
    1
    Rash
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperkeratosis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Dermatitis diaper
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    6
    0
    Muscle spasms
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Scoliosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 20 (20.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    9
    0
    Tinea pedis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Rhinitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Otitis externa
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    4 / 6 (66.67%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
         occurrences all number
    26
    2
    1
    Impetigo
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Herpes zoster
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Genital candidiasis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Cellulitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    COVID-19
         subjects affected / exposed
    3 / 6 (50.00%)
    11 / 20 (55.00%)
    1 / 7 (14.29%)
         occurrences all number
    3
    11
    1
    Bacterial infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Eczema impetiginous
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Influenza
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 20 (10.00%)
    2 / 7 (28.57%)
         occurrences all number
    3
    2
    3
    Herpangina
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Genital abscess
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    1
    Skin infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Otitis media
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Metabolism and nutrition disorders
    Abnormal weight gain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Pseudohypoglycaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 20 (15.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    3
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Dec 2021
    Screening period was updated to up to 28 days to make consistent with visit window for screening. also, Month 42 was added to header row to clarify and wrote down all specific visit timing in the case the extension period continued for 36 months.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 02 08:05:18 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA