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    Clinical Trial Results:
    A phase 3, open-label, randomized, multicenter, 12 months, efficacy and safety study of weekly mod-4023 compared to daily genotropin® therapy in pre-pubertal children with growth hormone deficiency

    Summary
    EudraCT number
    		 2016-003874-42
    Trial protocol
    		 GB   DE   BG   FR   PL   ES   GR   IT  
    Global end of trial date
    01 May 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Apr 2025
    First version publication date
    16 Apr 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CP-4-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02968004
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 79,745
    Sponsors
    Sponsor organisation name
    OPKO Biologics Ltd.
    Sponsor organisation address
    Ashlagan 16, Kiryat Gat,, Israel, 8211804
    Public contact
    OPKO Health, Inc., OPKO Health, Inc., 305 5754100, contact@opko.com
    Scientific contact
    OPKO Health, Inc., OPKO Health, Inc., 305 5754100, contact@opko.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 May 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Aug 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    01 May 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that annual (12 month) HV from weekly somatrogon administration is noninferior to daily Genotropin administration in children with GHD.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all ICH GCP Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects. The investigator, or a person designated by the investigator, obtained a signed and dated ICD from each subject’s parent(s)/guardian(s) before any study-specific activity was performed. Informed consent was collected as detailed in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Dec 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Bulgaria: 4
    Country: Number of subjects enrolled
    Belarus: 2
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Colombia: 8
    Country: Number of subjects enrolled
    Georgia: 6
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    India: 26
    Country: Number of subjects enrolled
    Israel: 15
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    Poland: 19
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    Taiwan: 2
    Country: Number of subjects enrolled
    Türkiye: 1
    Country: Number of subjects enrolled
    Ukraine: 24
    Country: Number of subjects enrolled
    United States: 42
    Country: Number of subjects enrolled
    United Kingdom: 3
    Worldwide total number of subjects
    224
    EEA total number of subjects
    45
    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)
    224
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Of the 228 subjects who were randomized, 4 subjects (3 in the somatrogon group; 1 in the Genotropin group) did not receive study drug (3 withdrawal by parent/guardian, 1 lost to follow-up during the screening phase). Therefore, 224 subjects were randomized and received at least 1 dose of study drug.

    Period 1
    Period 1 title
    Main Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MOD-4023 Main Study
    Arm description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MOD-4023
    Investigational medicinal product code
    Somatrogon
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Once weekly subcutaneous injection using pre-filled pen device.

    Arm title
    		 Genotropin Main Study
    Arm description
    		 Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Genotropin
    Investigational medicinal product code
    Somatropin
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Once daily subcutaneous injection of Genotropin

    Number of subjects in period 1
    		MOD-4023 Main Study Genotropin Main Study
    Started
    109
    115
    Completed
    108
    114
    Not completed
    1
    1
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    1
    -
    Period 2
    Period 2 title
    OLE Period
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 MOD-4023 OLE Peiod
    Arm description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MOD-4023
    Investigational medicinal product code
    Somatrogon
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Once weekly subcutaneous injection of long acting r-hGH (MOD-4023). MOD-4023: Once weekly subcutaneous injection using pre-filled pen device.

    Number of subjects in period 2 [1]
    		MOD-4023 OLE Peiod
    Started
    212
    Completed
    95
    Not completed
    117
         Closure of Epiphyseal Plates
    1
         Consent withdrawn by subject
    19
         Local Crisis
    21
         Adverse event, non-fatal
    9
         Miscellaneous Other
    4
         Non-Compliance With Study Drug
    1
         Prohibited Treatments
    1
         Sponsor Discontinuation of Study
    56
         Bone Age Reached
    5
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 10 Subjects which completed the main period, did not continue to OLE peiod

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MOD-4023 Main Study
    Reporting group description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

    Reporting group title
    Genotropin Main Study
    Reporting group description
    		 Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin)

    Reporting group values
    		 MOD-4023 Main Study Genotropin Main Study Total
    Number of subjects
    		 109 115 224
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 109 115 224
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 7.83 ( 2.66 ) 7.61 ( 2.37 ) -
    Gender categorical
    Units: Subjects
        Female
    		 27 36 63
        Male
    		 82 79 161
    Race
    Units: Subjects
        White
    		 81 86 167
        Black or African American
    		 0 2 2
        Asian
    		 24 21 45
        American Indian or Alaska Native
    		 1 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        Other
    		 3 5 8
        Unknown
    		 0 0 0
        MULTIRACIAL
    		 0 0 0
        Not reported
    		 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 11 13 24
        Not Hispanic or Latino
    		 98 102 200

    End points

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    End points reporting groups
    Reporting group title
    MOD-4023 Main Study
    Reporting group description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

    Reporting group title
    Genotropin Main Study
    Reporting group description
    		 Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin)
    Reporting group title
    MOD-4023 OLE Peiod
    Reporting group description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

    Subject analysis set title
    MOD-4023 OLE Year 1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects entered OLE period Year 1

    Subject analysis set title
    MOD-4023 OLE Year 2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects entered OLE period Year 2

    Subject analysis set title
    MOD-4023 OLE Year 3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects entered OLE period Year 3

    Subject analysis set title
    MOD-4023 OLE Year 4
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects entered OLE period Year 4

    Subject analysis set title
    MOD-4023 OLE Year 5
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects entered OLE period Year 5

    Primary: Annual Height Velocity 12 months

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    End point title
    		 Annual Height Velocity 12 months
    End point description
    Annual Height Velocity in cm. Annual Height Velocity at 12 months is based on the difference between the heights at 12 months and baseline.
    End point type
    Primary
    End point timeframe
    52 weeks
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    109
    115
    Units: centimetre
        arithmetic mean (confidence interval 95%)
    10.10 (9.58 to 10.63)
    9.78 (9.29 to 10.26)
    Statistical analysis title
    		 Annual HV at 12 Months
    Comparison groups
    Genotropin Main Study v MOD-4023 Main Study
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.05
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Height Velocity at 6 Months

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    End point title
    		 Height Velocity at 6 Months
    End point description
    Height velocity in cm measured after 6 months of treatment. Annualized Height velocity after 6 months is calculated based on the difference between the heights at 6 months and baseline.
    End point type
    Secondary
    End point timeframe
    After 6 months of treatment
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    109
    115
    Units: centimetre
        arithmetic mean (confidence interval 95%)
    10.59 (9.96 to 11.22)
    10.04 (9.47 to 10.62)
    No statistical analyses for this end point

    Secondary: Change in Height Standard Deviation Score (SDS)

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    End point title
    		 Change in Height Standard Deviation Score (SDS)
    End point description
    Change in height Standard Deviation Score (SDS) after 6 and 12 months is calculated based on the difference between the heights at 6 and 12 months and baseline.
    End point type
    Secondary
    End point timeframe
    After 6 and 12 months
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    109
    115
    Units: centimeter
    arithmetic mean (confidence interval 95%)
        6 mobths
    0.54 (0.48 to 0.61)
    0.48 (0.42 to 0.54)
        12 months
    0.92 (0.82 to 1.02)
    0.87 (0.78 to 0.96)
    No statistical analyses for this end point

    Secondary: Change in Bone Maturation (BM)

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    End point title
    		 Change in Bone Maturation (BM)
    End point description
    Annual change in bone age measurements as per Gruelich-Pyle method
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    104
    102
    Units: year
        arithmetic mean (standard deviation)
    0.05 ( 0.09 )
    0.06 ( 0.10 )
    No statistical analyses for this end point

    Secondary: Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) Baseline

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    End point title
    		 Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) Baseline
    End point description
    Via central lab analysis
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    109
    115
    Units: ng/m L
        arithmetic mean (standard deviation)
    -1.95 ( 0.89 )
    -1.72 ( 0.90 )
    No statistical analyses for this end point

    Secondary: Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) 12 Months

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    End point title
    		 Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) 12 Months
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 MOD-4023 Main Study Genotropin Main Study
    Number of subjects analysed
    107
    110
    Units: ng/ml
        arithmetic mean (standard deviation)
    0.65 ( 1.32 )
    -0.69 ( 1.09 )
    No statistical analyses for this end point

    Other pre-specified: Annualized Height Velocity at Each 12 Months in the OLE Period

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    End point title
    		 Annualized Height Velocity at Each 12 Months in the OLE Period
    End point description
    Annualized HV (cm/year): Annualized HV at each 12 months, based on the difference between the height at each 12 months and the height at the previous 12 months.
    End point type
    Other pre-specified
    End point timeframe
    12 months
    End point values
    		 MOD-4023 OLE Year 1 MOD-4023 OLE Year 2 MOD-4023 OLE Year 3 MOD-4023 OLE Year 4 MOD-4023 OLE Year 5
    Number of subjects analysed
    173
    173
    162
    75
    4
    Units: centimeter
        arithmetic mean (standard deviation)
    8.11 ( 1.84 )
    7.91 ( 1.84 )
    7.02 ( 1.75 )
    6.56 ( 1.91 )
    5.05 ( 1.10 )
    No statistical analyses for this end point

    Other pre-specified: Change in Height SDS in the OLE Period

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    End point title
    		 Change in Height SDS in the OLE Period
    End point description
    Change in height SDS, calculated as the difference between the height SDS at each scheduled visit in the OLE period and the height SDS at the main period baseline.
    End point type
    Other pre-specified
    End point timeframe
    12 months
    End point values
    		 MOD-4023 OLE Year 1 MOD-4023 OLE Year 2 MOD-4023 OLE Year 3 MOD-4023 OLE Year 4 MOD-4023 OLE Year 5
    Number of subjects analysed
    173
    173
    162
    75
    4
    Units: centimeter
        arithmetic mean (standard deviation)
    1.36 ( 0.75 )
    1.61 ( 0.78 )
    1.87 ( 0.85 )
    2.01 ( 0.75 )
    2.14 ( 0.38 )
    No statistical analyses for this end point

    Other pre-specified: Change in Bone Maturation at Each Visit in the OLE Period

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    End point title
    		 Change in Bone Maturation at Each Visit in the OLE Period
    End point description
    End point type
    Other pre-specified
    End point timeframe
    12 months
    End point values
    		 MOD-4023 OLE Year 1 MOD-4023 OLE Year 2 MOD-4023 OLE Year 3 MOD-4023 OLE Year 4 MOD-4023 OLE Year 5
    Number of subjects analysed
    165
    170
    156
    74
    6
    Units: year
        arithmetic mean (standard deviation)
    0.12 ( 0.13 )
    0.18 ( 0.16 )
    0.22 ( 0.16 )
    0.22 ( 0.16 )
    0.17 ( 0.18 )
    No statistical analyses for this end point

    Other pre-specified: Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) OLE Period

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    End point title
    		 Insulin-like Growth Factor-1 (IGF-1) Standard Deviation Score (SDS) OLE Period
    End point description
    IGF-1 levels and IGF-1 SDS levels on Day 4 (-1) after somatrogon dosing at every scheduled visit in the OLE Year 1 and at every 6 months thereafter. Change in IGF-1 SDS, calculated as the difference between the IGF-1 SDS values in the OLE period and the IGF-1 SDS at the main period baseline.
    End point type
    Other pre-specified
    End point timeframe
    6 months
    End point values
    		 MOD-4023 OLE Year 1 MOD-4023 OLE Year 2 MOD-4023 OLE Year 3 MOD-4023 OLE Year 4 MOD-4023 OLE Year 5
    Number of subjects analysed
    155
    169
    155
    70
    3
    Units: SDS +/- SD
        arithmetic mean (standard deviation)
    2.96 ( 1.20 )
    2.97 ( 1.20 )
    3.08 ( 1.21 )
    3.20 ( 1.06 )
    3.43 ( 0.16 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    1 year
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    MOD-4023 Main Study
    Reporting group description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

    Reporting group title
    Genotropin Main Study
    Reporting group description
    		 Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin)

    Reporting group title
    MOD-4023 OLE Period
    Reporting group description
    		 Once weekly subcutaneous injection of long acting r-hGH (MOD-4023)

    Serious adverse events
    		 MOD-4023 Main Study Genotropin Main Study MOD-4023 OLE Period
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 115 (1.74%)
    14 / 212 (6.60%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Kawasaki's disease
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Noninfective sialoadenitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Scrotal Varicose Veins
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 115 (0.87%)
    0 / 212 (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
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delayed puberty
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Chronic tonsillitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 115 (0.00%)
    0 / 212 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 115 (0.00%)
    0 / 212 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 115 (0.87%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    4 / 212 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Croup infectious
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    1 / 212 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 MOD-4023 Main Study Genotropin Main Study MOD-4023 OLE Period
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    92 / 109 (84.40%)
    90 / 115 (78.26%)
    192 / 212 (90.57%)
    General disorders and administration site conditions
    Injection Site Erythema
         subjects affected / exposed
    9 / 109 (8.26%)
    0 / 115 (0.00%)
    11 / 212 (5.19%)
         occurrences all number
    49
    0
    23
    Injection Site Induration
         subjects affected / exposed
    4 / 109 (3.67%)
    1 / 115 (0.87%)
    0 / 212 (0.00%)
         occurrences all number
    7
    1
    0
    Injection Site Pain
         subjects affected / exposed
    43 / 109 (39.45%)
    29 / 115 (25.22%)
    66 / 212 (31.13%)
         occurrences all number
    293
    80
    853
    Injection site pruritus
         subjects affected / exposed
    6 / 109 (5.50%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    10
    0
    13
    Injection Site Swelling
         subjects affected / exposed
    5 / 109 (4.59%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    9
    0
    9
    Pyrexia
         subjects affected / exposed
    18 / 109 (16.51%)
    16 / 115 (13.91%)
    40 / 212 (18.87%)
         occurrences all number
    35
    28
    116
    Vaccination Site Pain
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    8
    Immune system disorders
    Seasonal Allergy
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 109 (8.26%)
    9 / 115 (7.83%)
    24 / 212 (11.32%)
         occurrences all number
    10
    11
    37
    Nasal congestion
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 115 (2.61%)
    8 / 212 (3.77%)
         occurrences all number
    1
    3
    11
    Oropharyngeal pain
         subjects affected / exposed
    6 / 109 (5.50%)
    4 / 115 (3.48%)
    18 / 212 (8.49%)
         occurrences all number
    8
    6
    29
    Rhinitis allergic
         subjects affected / exposed
    3 / 109 (2.75%)
    1 / 115 (0.87%)
    5 / 212 (2.36%)
         occurrences all number
    8
    1
    7
    Rhinorrhoea
         subjects affected / exposed
    3 / 109 (2.75%)
    4 / 115 (3.48%)
    12 / 212 (5.66%)
         occurrences all number
    3
    7
    15
    Psychiatric disorders
    Attention Deficit/Hyperactivity Disorder
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    7 / 212 (3.30%)
         occurrences all number
    0
    0
    8
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 109 (1.83%)
    8 / 115 (6.96%)
    0 / 212 (0.00%)
         occurrences all number
    3
    8
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 109 (0.00%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    0
    3
    0
    Free fatty acids increased
         subjects affected / exposed
    5 / 109 (4.59%)
    1 / 115 (0.87%)
    11 / 212 (5.19%)
         occurrences all number
    7
    1
    16
    Insulin-Like Growth Factor Increased
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    6
    Low Density Lipoprotein Decreased
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    6
    Coronavirus Test Positive
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    15 / 212 (7.08%)
         occurrences all number
    0
    0
    15
    Thyroxine Free Decreased
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    7 / 212 (3.30%)
         occurrences all number
    0
    0
    7
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    6 / 109 (5.50%)
    1 / 115 (0.87%)
    0 / 212 (0.00%)
         occurrences all number
    11
    1
    0
    Ligament Sprain
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    7 / 212 (3.30%)
         occurrences all number
    0
    0
    9
    Limb Injury
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    6
    Skin Abrasion
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    8
    Contusion
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    6
    Fall
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    6
    Traumatic Fracture
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    18 / 109 (16.51%)
    25 / 115 (21.74%)
    41 / 212 (19.34%)
         occurrences all number
    39
    65
    107
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 109 (6.42%)
    7 / 115 (6.09%)
    5 / 212 (2.36%)
         occurrences all number
    8
    7
    9
    Iron deficiency anaemia
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 115 (1.74%)
    0 / 212 (0.00%)
         occurrences all number
    3
    2
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 109 (0.00%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    0
    3
    0
    Basophilia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    7
    Eosinophilia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    11 / 212 (5.19%)
         occurrences all number
    0
    0
    16
    Neutropenia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    5
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    2 / 109 (1.83%)
    7 / 115 (6.09%)
    7 / 212 (3.30%)
         occurrences all number
    2
    9
    10
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    3 / 109 (2.75%)
    0 / 115 (0.00%)
    0 / 212 (0.00%)
         occurrences all number
    3
    0
    0
    Myopia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    7
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 109 (3.67%)
    2 / 115 (1.74%)
    9 / 212 (4.25%)
         occurrences all number
    4
    3
    13
    Abdominal pain upper
         subjects affected / exposed
    2 / 109 (1.83%)
    6 / 115 (5.22%)
    12 / 212 (5.66%)
         occurrences all number
    2
    9
    19
    Constipation
         subjects affected / exposed
    2 / 109 (1.83%)
    4 / 115 (3.48%)
    5 / 212 (2.36%)
         occurrences all number
    3
    4
    6
    Diarrhoea
         subjects affected / exposed
    3 / 109 (2.75%)
    4 / 115 (3.48%)
    14 / 212 (6.60%)
         occurrences all number
    3
    4
    24
    Nausea
         subjects affected / exposed
    3 / 109 (2.75%)
    1 / 115 (0.87%)
    6 / 212 (2.83%)
         occurrences all number
    5
    2
    12
    Vomiting
         subjects affected / exposed
    8 / 109 (7.34%)
    9 / 115 (7.83%)
    23 / 212 (10.85%)
         occurrences all number
    16
    15
    41
    Toothache
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    6 / 212 (2.83%)
         occurrences all number
    0
    0
    8
    Dental Caries
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    9
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    1
    4
    0
    Rash
         subjects affected / exposed
    2 / 109 (1.83%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    2
    3
    0
    Rash generalised
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 115 (1.74%)
    0 / 212 (0.00%)
         occurrences all number
    3
    2
    0
    Urticaria
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    5
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    7 / 109 (6.42%)
    3 / 115 (2.61%)
    12 / 212 (5.66%)
         occurrences all number
    7
    3
    12
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 109 (4.59%)
    8 / 115 (6.96%)
    10 / 212 (4.72%)
         occurrences all number
    8
    12
    18
    Pain in extremity
         subjects affected / exposed
    5 / 109 (4.59%)
    5 / 115 (4.35%)
    10 / 212 (4.72%)
         occurrences all number
    5
    8
    13
    Scoliosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    8 / 212 (3.77%)
         occurrences all number
    0
    0
    8
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    3 / 109 (2.75%)
    9 / 115 (7.83%)
    15 / 212 (7.08%)
         occurrences all number
    4
    14
    18
    Enterobiasis
         subjects affected / exposed
    4 / 109 (3.67%)
    2 / 115 (1.74%)
    0 / 212 (0.00%)
         occurrences all number
    5
    4
    0
    Gastroenteritis
         subjects affected / exposed
    4 / 109 (3.67%)
    3 / 115 (2.61%)
    8 / 212 (3.77%)
         occurrences all number
    5
    3
    12
    Gastroenteritis viral
         subjects affected / exposed
    0 / 109 (0.00%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    0
    3
    0
    Influenza
         subjects affected / exposed
    5 / 109 (4.59%)
    3 / 115 (2.61%)
    22 / 212 (10.38%)
         occurrences all number
    8
    5
    28
    Molluscum contagiosum
         subjects affected / exposed
    3 / 109 (2.75%)
    0 / 115 (0.00%)
    0 / 212 (0.00%)
         occurrences all number
    4
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    25 / 109 (22.94%)
    29 / 115 (25.22%)
    66 / 212 (31.13%)
         occurrences all number
    54
    52
    164
    Otitis externa
         subjects affected / exposed
    4 / 109 (3.67%)
    4 / 115 (3.48%)
    0 / 212 (0.00%)
         occurrences all number
    4
    4
    0
    Otitis media
         subjects affected / exposed
    4 / 109 (3.67%)
    7 / 115 (6.09%)
    9 / 212 (4.25%)
         occurrences all number
    6
    8
    28
    Otitis media acute
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    1
    4
    0
    Pharyngitis
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 115 (4.35%)
    7 / 212 (3.30%)
         occurrences all number
    10
    7
    14
    Rhinitis
         subjects affected / exposed
    6 / 109 (5.50%)
    1 / 115 (0.87%)
    10 / 212 (4.72%)
         occurrences all number
    9
    2
    19
    Tonsillitis
         subjects affected / exposed
    5 / 109 (4.59%)
    6 / 115 (5.22%)
    6 / 212 (2.83%)
         occurrences all number
    6
    7
    8
    Conjunctivitis
         subjects affected / exposed
    3 / 109 (2.75%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    3
    3
    0
    Corona Virus Infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    37 / 212 (17.45%)
         occurrences all number
    0
    0
    52
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    12 / 212 (5.66%)
         occurrences all number
    0
    0
    17
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    7 / 212 (3.30%)
         occurrences all number
    0
    0
    12
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    7 / 212 (3.30%)
         occurrences all number
    0
    0
    12
    Pneumonia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    5
    Sinusitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    7
    Viral Infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    5
    Viral Pharyngitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 115 (0.00%)
    5 / 212 (2.36%)
         occurrences all number
    0
    0
    7
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 109 (2.75%)
    0 / 115 (0.00%)
    0 / 212 (0.00%)
         occurrences all number
    3
    0
    0
    Hypoinsulinaemia
         subjects affected / exposed
    4 / 109 (3.67%)
    3 / 115 (2.61%)
    6 / 212 (2.83%)
         occurrences all number
    4
    3
    8
    Iron deficiency
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 115 (2.61%)
    0 / 212 (0.00%)
         occurrences all number
    1
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jan 2018
    ROW Version 3.0 (23 January 2018) Protocol Amendment 1 Countries used: Taiwan, Argentina, Colombia, Bulgaria, Greece, Turkey Increased the frequency and timing of the serum sampling schedule for immunogenicity assessment (at 10-14 days; at 1, 3, 6, 9, and 12 months. Updated statistical analyses sections to align with the SAP (Amendment 2, Version 3.0, 23 January 2018).
    21 Feb 2018
    ROW+QoL Version 2.0 (21 February 2018) Protocol Amendment 1 Countries used: Spain, Australia, New-Zealand, Russia, UK Increased the frequency and timing of the serum sampling schedule for immunogenicity assessment (at 10-14 days; at 1, 3, 6, 9, and 12 months. Updated statistical analyses sections to align with the SAP (Amendment 2, Version 3.0, 23 January 2018).
    09 May 2018
    ROW Version 4.0 (09 May 2018) Protocol Amendment 2 Countries used: Georgia, Poland, Taiwan, Argentina, Mexico, Bulgaria, Greece, Turkey, Israel, Canada The subject of this amendment is the inclusion of an open label extension (OLE) to the study to capture those patients that have successfully completed the 12 months of dosing in the Main Study and continue to meet inclusion / exclusion criteria.
    09 May 2018
    ROW+QoL Version 3.0 (09 May 2018) Protocol Amendment 2 Countries used: Spain, Australia, New Zealand, Russia, UK, Ukraine, Belarus The subject of this amendment is the inclusion of an open label extension (OLE) to the study to capture those patients that have successfully completed the 12 months of dosing in the Main Study and continue to meet inclusion / exclusion criteria.

    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
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