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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Open-Label, Comparator-Controlled Study to Assess Safety and Tolerability of Weekly TV-1106 Compared to Daily rhGH (GENOTROPIN®1) in Adults with Growth Hormone-Deficiency

    Summary
    EudraCT number
    2014-002736-13
    Trial protocol
    DE   HU   SE   IT   AT   ES   SI   LT   GR   CZ   PL   SK   HR  
    Global end of trial date
    18 Dec 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    26 Dec 2016
    First version publication date
    26 Dec 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    TV1106-IMM-30022
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02410356
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Teva Pharmaceutical Industries Ltd.
    Sponsor organisation address
    5 Bazel Street, Petach Tikva, Israel, 49131
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info-era-clinical@teva.de
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 215-591-3000, info-era-clinical@teva.de
    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
    19 Sep 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Dec 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to compare the safety and tolerability of weekly TV-1106 with daily Genotropin. Based on evolving data from the two ongoing global Phase III studies in adults (TV1106-IMM-30021 and -30022) and the ongoing pediatric Phase II study (TV1106-IMM-20001) and as well as the recently completed adult Phase II study (TV1106-GHD-201), the Sponsor Teva Pharmaceuticals Ltd. reassessed the benefit/risk balance of TV-1106 and the likelihood of regulatory success for TV-1106. As a consequence of this reassessment, the Sponsor took the decision to terminate the development of TV- 1106 and stop all ongoing clinical trials. Notably, no new safety issues were identified with the administration of TV-1106.
    Protection of trial subjects
    This study was conducted in full accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations Title 21, Parts 50, 54, 56, 312, and 314; EU Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use). Written and/or oral information about the study was provided to all patients in a language understandable by the patients. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each patient before any study procedures or assessments were done. It was explained to the patients that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment. Each patient’s willingness to participate in the study was documented in writing in a consent form that was signed by the patient with the date of that signature indicated. Each investigator kept the original consent forms, and copies were given to the patients.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Apr 2015
    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
    Hungary: 2
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    34
    EEA total number of subjects
    2
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    25
    From 65 to 84 years
    8
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    78 patients with GHD were screened for enrollment. 34 patients at 10 centers in the US and Hungary met entry criteria and were considered eligible for randomization. 44 patients who were not randomly assigned to study treatment: 18 were excluded due to inclusion/exclusion criteria and 26 were excluded for “other” reasons.

    Pre-assignment
    Screening details
    Eligible patients were randomly assigned to receive treatment with TV-1106 or GENOTROPIN in a 4:1 allocation ratio stratified by a combination of gender and oral estrogen use at screening (female using oral estrogen, female not using oral estrogen, and male).

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    TV-1106
    Arm description
    TV-1106 was injected once weekly on the same day and at approximately the same time (between 1800 and 2200) for the 48-week open-label treatment. The starting dose of TV-1106 was determined by multiplying the individual starting dose of previously taken daily rhGH (eg, GENOTROPIN) by a conversion factor of 28. The TV-1106 dose was adjusted so that the patient’s dose resulted in IGF-1 SDS between -0.5 and +1.5.
    Arm type
    Experimental

    Investigational medicinal product name
    TV-1106
    Investigational medicinal product code
    Other name
    long-acting growth hormone, albutropin
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    TV-1106 was administered on a weekly basis subcutaneously, either self-administered or administered during visits to the study site. The TV-1106 dose was adjusted so that the patient’s dose resulted in IGF-1 SDS between -0.5 and +1.5. Dose increments were 2.5 mg or 5.0 mg based on patient demographics.

    Arm title
    Genotropin
    Arm description
    The dose levels of GENOTROPIN were the same as the stable rhGH dose taken by each patient before the study, and were expected to range from 0.2 to 1.8 mg. GENOTROPIN was given as a daily subcutaneous injection for 48 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Genotropin
    Investigational medicinal product code
    Other name
    GENOTROPIN®, somatropin [rDNA origin]
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose levels of GENOTROPIN were the same as the stable rhGH dose taken by each patient before the study, and were expected to range from 0.2 to 1.8 mg. GENOTROPIN was given as a daily subcutaneous injection.

    Number of subjects in period 1
    TV-1106 Genotropin
    Started
    27
    7
    Completed
    0
    0
    Not completed
    27
    7
         Sponsor terminated the study
    27
    6
         Consent withdrawn by subject
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TV-1106
    Reporting group description
    TV-1106 was injected once weekly on the same day and at approximately the same time (between 1800 and 2200) for the 48-week open-label treatment. The starting dose of TV-1106 was determined by multiplying the individual starting dose of previously taken daily rhGH (eg, GENOTROPIN) by a conversion factor of 28. The TV-1106 dose was adjusted so that the patient’s dose resulted in IGF-1 SDS between -0.5 and +1.5.

    Reporting group title
    Genotropin
    Reporting group description
    The dose levels of GENOTROPIN were the same as the stable rhGH dose taken by each patient before the study, and were expected to range from 0.2 to 1.8 mg. GENOTROPIN was given as a daily subcutaneous injection for 48 weeks.

    Reporting group values
    TV-1106 Genotropin Total
    Number of subjects
    27 7 34
    Age categorical
    Units: Subjects
        <40 years
    1 2 3
        >=40 years
    26 5 31
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    56.1 ± 13.31 55.9 ± 16.59 -
    Gender categorical
    Units: Subjects
        Female
    11 3 14
        Male
    16 4 20
    Race
    Units: Subjects
        White
    21 7 28
        Black
    2 0 2
        Asian
    2 0 2
        Missing
    2 0 2
    Growth-Hormone Deficiency Onset
    Units: Subjects
        Adult (>+18 years)
    24 6 30
        Childhood (<18 years)
    3 1 4
    Cause of Growth-Hormone Deficiency
    Units: Subjects
        Traumatic brain injury
    2 0 2
        Non-secreting pituitary adenoma
    8 2 10
        Idiopathic
    15 3 18
        Craniopharyngioma
    1 1 2
        Other
    1 1 2
    Prior Treatment for Growth-Hormone Deficiency
    Units: Subjects
        Yes
    27 7 34
        No
    0 0 0
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    86.31 ± 15.5853 81.343 ± 20.5136 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    172.77 ± 9.5527 166.729 ± 14.5053 -
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    28.732 ± 3.4828 28.926 ± 4.6681 -
    Insulin-like Growth Factor 1 Standard Deviation Score
    IGF-1 SDS represents the standard deviation from a 'normal' population.
    Units: standard deviations
        arithmetic mean (standard deviation)
    0.36 ± 0.644 0.41 ± 0.495 -
    Duration of Growth-Hormone Deficiency Diagnosis
    Units: years
        arithmetic mean (standard deviation)
    9.56 ± 9.7143 12.734 ± 12.4567 -

    End points

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    End points reporting groups
    Reporting group title
    TV-1106
    Reporting group description
    TV-1106 was injected once weekly on the same day and at approximately the same time (between 1800 and 2200) for the 48-week open-label treatment. The starting dose of TV-1106 was determined by multiplying the individual starting dose of previously taken daily rhGH (eg, GENOTROPIN) by a conversion factor of 28. The TV-1106 dose was adjusted so that the patient’s dose resulted in IGF-1 SDS between -0.5 and +1.5.

    Reporting group title
    Genotropin
    Reporting group description
    The dose levels of GENOTROPIN were the same as the stable rhGH dose taken by each patient before the study, and were expected to range from 0.2 to 1.8 mg. GENOTROPIN was given as a daily subcutaneous injection for 48 weeks.

    Primary: Percentage of Participants with Treatment-emergent Adverse Events

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    End point title
    Percentage of Participants with Treatment-emergent Adverse Events [1]
    End point description
    An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 35
    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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [2]
    7 [3]
    Units: percentage of total participants
    number (not applicable)
        >=1 adverse event
    51.9
    57.1
        Severe adverse event
    0
    0
        Treatment-related adverse event
    14.8
    14.3
        Deaths
    0
    0
        Other serious adverse events
    0
    0
        Discontinued from study drug due to adverse events
    0
    0
    Notes
    [2] - Safety population
    [3] - Safety population
    No statistical analyses for this end point

    Primary: Percentage of Participants with Potentially Clinically Significant Abnormal Blood and Urine Test Results

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    End point title
    Percentage of Participants with Potentially Clinically Significant Abnormal Blood and Urine Test Results [4]
    End point description
    Parameters with potentially clinically significant abnormal test results include - Serum chemistry: gamma glutamyl transferase - Hematology: leukocytes, eosinophils/leukocytes - Urinalysis: ketones Significance criteria are listed below with the test. ULN = upper limit of normal
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 35
    Notes
    [4] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [5]
    7 [6]
    Units: percentage of total participants
    number (not applicable)
        Gamma glutamyl transferase: >=3*ULN
    3.7
    0
        Leukocytes: <=3.0 10^9/L
    3.7
    0
        Eosinophils/leukocytes: >=10.0%
    7.4
    0
        Ketones: >=2 unit increase from baseline
    0
    14.3
    Notes
    [5] - Safety population
    [6] - Safety population
    No statistical analyses for this end point

    Primary: Percentage of Participants with Potentially Clinically Significant Vital Signs

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    End point title
    Percentage of Participants with Potentially Clinically Significant Vital Signs [7]
    End point description
    Significance criteria for vital signs that showed potentially clinically significant findings are: - Pulse rate: decrease 15 beats per minute (bpm) to <= 50 bpm - Diastolic blood pressure: decrease 15 mmHg to <= 50 mmHg
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 35
    Notes
    [7] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [8]
    7 [9]
    Units: percentage of total participants
    number (not applicable)
        Pulse rate
    3.7
    14.3
        Diastolic blood pressure
    0
    14.3
    Notes
    [8] - Safety population
    [9] - Safety population
    No statistical analyses for this end point

    Primary: Shift From Baseline To Endpoint in Electrocardiogram Findings

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    End point title
    Shift From Baseline To Endpoint in Electrocardiogram Findings [10]
    End point description
    Shifts represented as baseline - endpoint value (last observed post-baseline value). Endpoint is the last observed value. Abnormal NCS indicates an abnormal but not clinically significant finding. Abnormal CS indicates an abnormal and clinically significant finding. Values of 'Missing' indicate patients who did not have both a baseline and treatment finding.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [10] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [11]
    7 [12]
    Units: participants
        Normal - Normal
    14
    3
        Normal - Abnormal NCS
    4
    1
        Normal - Abnormal CS
    0
    0
        Abnormal NCS - Normal
    0
    0
        Abnormal NCS - Abnormal NCS
    8
    2
        Abnormal NCS - Abnormal CS
    0
    0
        Missing
    1
    1
    Notes
    [11] - Safety population
    [12] - Safety population
    No statistical analyses for this end point

    Primary: Thyroid Stimulating Hormone (TSH) Values at Baseline and Endpoint

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    End point title
    Thyroid Stimulating Hormone (TSH) Values at Baseline and Endpoint [13]
    End point description
    Observed values of TSH which is the first of three thyroid hormones measured.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [13] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [14]
    7 [15]
    Units: MIU/L
    arithmetic mean (standard deviation)
        Baseline (n=27, 5)
    1.593 ± 1.5431
    1.702 ± 0.6426
        Endpoint (n=27, 6)
    1.522 ± 1.1972
    1.592 ± 1.3742
    Notes
    [14] - Safety population
    [15] - Safety population
    No statistical analyses for this end point

    Primary: Free Thyroxin (free T4) Values at Baseline and Endpoint

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    End point title
    Free Thyroxin (free T4) Values at Baseline and Endpoint [16]
    End point description
    Observed values of Free T4 which is the second of three thyroid hormones measured.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [16] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [17]
    7 [18]
    Units: PMOL/L
    arithmetic mean (standard deviation)
        Baseline (n=27, 7)
    14.71 ± 2.597
    15.61 ± 3.09
        Endpoint (n=27, 6)
    15.27 ± 2.384
    15.45 ± 4.457
    Notes
    [17] - Safety population
    [18] - Safety population
    No statistical analyses for this end point

    Primary: Triiodothyronine (Total T3) Values at Baseline and Endpoint

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    End point title
    Triiodothyronine (Total T3) Values at Baseline and Endpoint [19]
    End point description
    Observed values of Total T3 which is the third of three thyroid hormones measured.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [19] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [20]
    7 [21]
    Units: NMOL/L
    arithmetic mean (standard deviation)
        Baseline (n=27, 7)
    1.54 ± 0.283
    1.21 ± 0.406
        Endpoint (n=27, 6)
    1.48 ± 0.283
    1.33 ± 0.393
    Notes
    [20] - Safety population
    [21] - Safety population
    No statistical analyses for this end point

    Primary: Glycated Hemoglobin (HbA1c) Values at Baseline and Endpoint

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    End point title
    Glycated Hemoglobin (HbA1c) Values at Baseline and Endpoint [22]
    End point description
    Glycated Hemoglobin (HbA1c) is a measure of glucose homeostasis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [22] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [23]
    7 [24]
    Units: percentage of total hemoglobin
    arithmetic mean (standard deviation)
        Baseline (n=26, 7)
    5.62 ± 0.583
    5.79 ± 0.861
        Endpoint (n=27, 6)
    5.62 ± 0.672
    5.9 ± 1.203
    Notes
    [23] - Safety population
    [24] - Safety population
    No statistical analyses for this end point

    Primary: Fasting Blood Glucose Values at Baseline and Endpoint

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    End point title
    Fasting Blood Glucose Values at Baseline and Endpoint [25]
    End point description
    Fasting blood glucose is another measure of glucose homeostasis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [25] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [26]
    7 [27]
    Units: MMOL/L
    arithmetic mean (standard deviation)
        Baseline (n=27, 7)
    5.56 ± 1.361
    5.51 ± 1.271
        Endpoint (n=27, 6)
    5.43 ± 1.106
    5.88 ± 1.533
    Notes
    [26] - Safety population
    [27] - Safety population
    No statistical analyses for this end point

    Primary: Insulin Values at Baseline and Endpoint

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    End point title
    Insulin Values at Baseline and Endpoint [28]
    End point description
    Insulin is another measure of glucose homeostasis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, pre-dose), Endpoint (up to Week 35)
    Notes
    [28] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [29]
    7 [30]
    Units: PMOL/L
    arithmetic mean (standard deviation)
        Baseline (n=27, 7)
    81.1 ± 57.34
    76.3 ± 54.19
        Endpoint (n=27, 6)
    83.3 ± 49.63
    52 ± 17.66
    Notes
    [29] - Safety population
    [30] - Safety population
    No statistical analyses for this end point

    Primary: Local Tolerability Assessed by Injection Site Reactions

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    End point title
    Local Tolerability Assessed by Injection Site Reactions [31]
    End point description
    Participants reporting at least one injection site reaction.
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 35
    Notes
    [31] - 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: Because the study was terminated while enrollment was ongoing, the sample size was smaller than the planned 140 patients; 34 patients enrolled, 7 of whom received GENOTROPIN and 27 of whom received TV-1106 . Thus limited analyses were completed and no conclusions were reached.
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [32]
    7 [33]
    Units: percentage of total participants
    number (not applicable)
        Pain
    0
    14.3
        Tenderness
    0
    0
        Erythema
    0
    0
        Warmth
    0
    0
        Swelling
    0
    0
    Notes
    [32] - Safety population
    [33] - Safety population
    No statistical analyses for this end point

    Secondary: Peak and Trough Insulin-Like Growth Factor 1 Standard Deviation Scores (IGF-I SDS) During the Study

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    End point title
    Peak and Trough Insulin-Like Growth Factor 1 Standard Deviation Scores (IGF-I SDS) During the Study
    End point description
    Peak reflects maximum value of IGF-I SDS from samples taken on Days 1 or 2 following TV-1106 dose (at Weeks 4, 8, & 16). For Genotropin, peak is the maximum IGF-I SDS value across the entire study. Trough reflects minimum value of IGF-I SDS results from samples taken on Day 7, just prior to the next dose of TV-1106 (at Weeks 12 and 24). For Genotropin, trough is the minimum IGF-I SDS value across the entire study.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Week 35
    End point values
    TV-1106 Genotropin
    Number of subjects analysed
    27 [34]
    7 [35]
    Units: standard deviations
    arithmetic mean (standard deviation)
        Peak IGF-1 SDS (n=20, 6)
    0.91 ± 0.934
    1.32 ± 0.591
        Trough IGF-1 SDS (n=17, 6)
    0.25 ± 0.571
    0.5 ± 0.707
    Notes
    [34] - Safety population
    [35] - Safety population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to Week 35
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    TV-1106
    Reporting group description
    TV-1106 was injected once weekly on the same day and at approximately the same time (between 1800 and 2200) for the 48-week open-label treatment. The starting dose of TV-1106 was determined by multiplying the individual starting dose of previously taken daily rhGH (eg, GENOTROPIN) by a conversion factor of 28. The TV-1106 dose was adjusted so that the patient’s dose resulted in IGF-1 SDS between -0.5 and +1.5.

    Reporting group title
    Genotropin
    Reporting group description
    The dose levels of GENOTROPIN were the same as the stable rhGH dose taken by each patient before the study, and were expected to range from 0.2 to 1.8 mg. GENOTROPIN was given as a daily subcutaneous injection for 48 weeks.

    Serious adverse events
    TV-1106 Genotropin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 7 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    TV-1106 Genotropin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 27 (33.33%)
    4 / 7 (57.14%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    Eye disorders
    Ocular discomfort
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 27 (14.81%)
    0 / 7 (0.00%)
         occurrences all number
    4
    0
    Injection site pain
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    Large intestine polyp
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Infections and infestations
    Viral sinusitis
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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.
    The sample size was smaller than the planned 140 patients; 34 patients enrolled. Limited analyses were completed and no conclusions reached.
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