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    Clinical Trial Results:
    An Open Label Extension Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) Beta-thalassemia Subjects

    Summary
    EudraCT number
    		 2018-004423-36
    Trial protocol
    		 GR   GB   IT  
    Global end of trial date
    31 Jul 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Apr 2021
    First version publication date
    01 Apr 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PTG-300-03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04054921
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 137605
    Sponsors
    Sponsor organisation name
    Protagonist Therapeutics Inc.
    Sponsor organisation address
    7707 Gateway Blvd, Suite 140, Newark, United States, CA 94560
    Public contact
    Clinical-Regulatory Info Group, Protagonist Therapeutics, Inc., 001 510 4740170, clinregops@ptgx-inc.com
    Scientific contact
    Clinical-Regulatory Info Group, Protagonist Therapeutics, Inc., 001 510 4740170, clinregops@ptgx-inc.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
    31 Jul 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jul 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1.To assess the long-term safety and tolerability of PTG-300 in subjects with TD and NTD β-thalassemia
    Protection of trial subjects
    The trial was conducted in compliance with the moral, ethical and scientific principles governing clinical research as set out in the current Declaration of Helsinki, and the guidelines on Good Clinical Practice (GCP). The trial was conducted in accordance with the ethical principles of Good Clinical Practice, according to the ICH Harmonized Tripartite Guideline.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Apr 2019
    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
    United Kingdom: 1
    Country: Number of subjects enrolled
    Greece: 12
    Country: Number of subjects enrolled
    Lebanon: 5
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Thailand: 18
    Country: Number of subjects enrolled
    Malaysia: 12
    Country: Number of subjects enrolled
    Tunisia: 5
    Worldwide total number of subjects
    63
    EEA total number of subjects
    12
    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)
    4
    Adults (18-64 years)
    59
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at a total of 35 sites, including sites in North America, Europe, Asia and the Middle East. First NTD β-Thalassemia patients enrolled 31/03/2019. First TD β-Thalassemia patients enrolled 28/04/2019.

    Pre-assignment
    Screening details
    		 11 out of 24 NTD, and 23 out of 39 TD β-Thalassemia patients successfully completed week 12 and 16 of study PTG-300-02, and met the eligibility criteria for rolling over to study PTG-300-03. 16 TD and 13 NTD subjects in study PTG-300-02 either discontinued early, or did not meet the eligibility criteria for rolling over to study PTG-300-03.

    Period 1
    Period 1 title
    Treatment Phase (long-term extension) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Patients with NTD β-Thalassemia
    Arm description
    		 Patients aged 12- 65 with NTD β-Thalassemia who completed week 12 of study PTG-300-02, and met the criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of NTD β-Thalassemia patients reported for study PTG-300-03 reflects the number of NTD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PTG-300
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous administration of PTG-300 was done weekly, every 2 weeks, or twice weekly based on individual patient’s dosing needs. PTG-300 was administered at the study site or at home by the patient, caregiver or home nurse, after adequate training had been imparted and documented. Dosing window for weekly administration was ±2 days. Dosing window for twice weekly administration was ±1 day.

    Arm title
    		 Patients with TD β-Thalassemia
    Arm description
    		 Patients aged 12-65 with TD β-Thalassemia who completed week 16 of study PTG-300-02 and met the eligibility criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of TD β-Thalassemia patients reported for study PTG-300-03 reflects the number of TD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PTG-300
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous administration of PTG-300 was done weekly, every 2 weeks, or twice weekly based on individual patient’s dosing needs. PTG-300 was administered at the study site or at home by the patient, caregiver or home nurse, after adequate training had been imparted and documented. Dosing window for weekly administration was ±2 days. Dosing window for twice weekly administration was ±1 day.

    Number of subjects in period 1
    		Patients with NTD β-Thalassemia Patients with TD β-Thalassemia
    Started
    24
    39
    Titration phase
    24
    39
    Maintenance phase
    0
    0
    Completed
    0
    0
    Not completed
    24
    39
         Study terminated prior to completion by Sponsor
    24
    39

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Patients with NTD β-Thalassemia
    Reporting group description
    		 Patients aged 12- 65 with NTD β-Thalassemia who completed week 12 of study PTG-300-02, and met the criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of NTD β-Thalassemia patients reported for study PTG-300-03 reflects the number of NTD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.

    Reporting group title
    Patients with TD β-Thalassemia
    Reporting group description
    		 Patients aged 12-65 with TD β-Thalassemia who completed week 16 of study PTG-300-02 and met the eligibility criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of TD β-Thalassemia patients reported for study PTG-300-03 reflects the number of TD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.

    Reporting group values
    		 Patients with NTD β-Thalassemia Patients with TD β-Thalassemia Total
    Number of subjects
    		 24 39 63
    Age categorical
    Units: Subjects
        Adults aged 18-65 years
    		 23 36 59
        Adolescents aged 12-<18 years
    		 1 3 4
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 35 ( 10.5 ) 38 ( 13.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 9 17 26
        Male
    		 15 22 37
    Race
    Units: Subjects
        White
    		 10 20 30
        Asian
    		 14 17 31
        Other
    		 0 1 1
        Not reported
    		 0 1 1
    Subject analysis sets

    Subject analysis set title
    TD safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    β-Thalassemia patients belonging to the transfusion dependent (TD) subpopulation, who received at least one dose of study drug.

    Subject analysis set title
    NTD safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    β-Thalassemia patients belonging to the non-transfusion dependent (NTD) subpopulation, who received at least one dose of study drug.

    Subject analysis sets values
    		 TD safety population NTD safety population
    Number of subjects
    39
    24
    Age categorical
    Units: Subjects
        Adults aged 18-65 years
    36
    23
        Adolescents aged 12-<18 years
    3
    1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    38 ( 13.5 )
    35 ( 10.5 )
    Gender categorical
    Units: Subjects
        Female
    17
    9
        Male
    22
    15
    Race
    Units: Subjects
        White
    20
    10
        Asian
    17
    14
        Other
    1
    0
        Not reported
    1
    0

    End points

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    End points reporting groups
    Reporting group title
    Patients with NTD β-Thalassemia
    Reporting group description
    		 Patients aged 12- 65 with NTD β-Thalassemia who completed week 12 of study PTG-300-02, and met the criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of NTD β-Thalassemia patients reported for study PTG-300-03 reflects the number of NTD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.

    Reporting group title
    Patients with TD β-Thalassemia
    Reporting group description
    		 Patients aged 12-65 with TD β-Thalassemia who completed week 16 of study PTG-300-02 and met the eligibility criteria for study PTG-300-03. PTG-300-03 is an extension of Study PTG-300-02. The analysis of responders is based on the combined data from PTG-300-02 and PTG-300-03 studies. Therefore, the number of TD β-Thalassemia patients reported for study PTG-300-03 reflects the number of TD β-Thalassemia patients who enrolled in study PTG-300-02, and not the number of patients who enrolled in study PTG-300-03.

    Subject analysis set title
    TD safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    β-Thalassemia patients belonging to the transfusion dependent (TD) subpopulation, who received at least one dose of study drug.

    Subject analysis set title
    NTD safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    β-Thalassemia patients belonging to the non-transfusion dependent (NTD) subpopulation, who received at least one dose of study drug.

    Primary: Proportion of responders

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    End point title
    		 Proportion of responders [1] [2]
    End point description
    Proportion of responders at each dose, where responders are defined as patients who achieve ≥ 20% reduction in the red blood cell units required over an 8-week period compared to pre-treatment baseline.
    End point type
    Primary
    End point timeframe
    8 weeks post-dose.
    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: Only descriptive statistical analyses were performed during the study.
    [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: Only descriptive statistical analyses were performed during the study.
    End point values
    		 Patients with TD β-Thalassemia
    Number of subjects analysed
    37 [3]
    Units: Number of responders
        3mg/week
    1
        10mg/week
    2
        20mg/week
    1
        40mg/week
    3
        80mg/week
    7
        40mg 2x/week
    2
        Any dose level
    12
    Notes
    [3] - 2 patients removed from the efficacy analysis due to issues of site non-compliance.
    No statistical analyses for this end point

    Primary: Proportion of responders

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    End point title
    		 Proportion of responders [4] [5]
    End point description
    Proportion of responders at each dose, where responders are defined as patients who achieve an increase in Hgb ≥ 1.0 g/dL from pre-treatment baseline without transfusion, (confirmed by a successive measurement at least 1 week later.)
    End point type
    Primary
    End point timeframe
    4, 8 and 12 weeks post dose.
    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: Only descriptive statistical analyses were performed during the study.
    [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: Only descriptive statistical analyses were performed during the study.
    End point values
    		 Patients with NTD β-Thalassemia
    Number of subjects analysed
    23 [6]
    Units: Number of responders
        3mg/week
    0
        10mg/week
    0
        20mg/week
    0
        40mg/week
    0
        80mg/week
    0
        40mg 2x/week
    0
    Notes
    [6] - 1 patient removed from the efficacy analysis due to issues of site non-compliance.
    No statistical analyses for this end point

    Primary: Red blood cell units required

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    End point title
    		 Red blood cell units required [7] [8]
    End point description
    Mean change from pre-treatment baseline in the number of red blood cell units required under each dose (standardised to 8-week period.)
    End point type
    Primary
    End point timeframe
    8 weeks post-dose
    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: Only descriptive statistical analyses were performed during the study.
    [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: Only descriptive statistical analyses were performed during the study.
    End point values
    		 Patients with TD β-Thalassemia
    Number of subjects analysed
    37 [9]
    Units: Transfusion units
    arithmetic mean (standard deviation)
        3mg/week
    0.46 ( 1.194 )
        10mg/week
    0.53 ( 1.291 )
        20mg/week
    0.49 ( 1.127 )
        40mg/week
    0.07 ( 0.953 )
        80mg/week
    -0.16 ( 1.756 )
        40mg 2x/week
    -0.00 ( 1.075 )
        Any dose level
    -0.21 ( 1.188 )
    Notes
    [9] - 2 patients removed from the efficacy analysis due to issues of site non-compliance.
    No statistical analyses for this end point

    Primary: Hemoglobin change

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    End point title
    		 Hemoglobin change [10] [11]
    End point description
    Mean Hemoglobin change from pre-treatment baseline at each dose level.
    End point type
    Primary
    End point timeframe
    4, 8 and 12 weeks.
    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: Only descriptive statistical analyses were performed during the study.
    [11] - 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: Only descriptive statistical analyses were performed during the study.
    End point values
    		 Patients with NTD β-Thalassemia
    Number of subjects analysed
    23 [12]
    Units: Hemoglobin (g/dL)
    arithmetic mean (standard deviation)
        3mg/week
    -0.25 ( 1.184 )
        10mg/week
    -0.09 ( 0.639 )
        20mg/week
    -0.16 ( 0.638 )
        40mg/week
    -0.42 ( 0.602 )
        80mg/week
    -0.83 ( 0.682 )
        40mg 2x/week
    -1.10 ( 0.212 )
    Notes
    [12] - -1 patient removed from the efficacy analysis due to issues of site non-compliance
    No statistical analyses for this end point

    Other pre-specified: Liver iron content

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    End point title
    		 Liver iron content
    End point description
    Change in mean liver iron load from baseline to the last MRI performed for TD patients undergoing MRI evaluation.
    End point type
    Other pre-specified
    End point timeframe
    From baseline to last MRI performed.
    End point values
    		 Patients with NTD β-Thalassemia Patients with TD β-Thalassemia
    Number of subjects analysed
    15
    29
    Units: mg Fe/ g dry weight
    arithmetic mean (standard deviation)
        10mg/week
    -0.60 ( 0 )
    -0.23 ( 2.499 )
        20mg/week
    -1.88 ( 4.568 )
    -0.55 ( 1.826 )
        40mg/week
    1.93 ( 1.590 )
    0.94 ( 3.304 )
        80mg/week
    -2.04 ( 7.116 )
    -9.33 ( 16.868 )
        40mg 2x/week
    0.60 ( 0 )
    -4.2 ( 6.223 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment related adverse events (TEAEs, including serious adverse events (SAEs)) were reported from first dose until 30 days post last PTG-300 dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    TD patients
    Reporting group description
    		 All subjects treated with the study product were considered eligible for safety evaluation.

    Reporting group title
    NTD patients
    Reporting group description
    		 All subjects treated with the study product were considered eligible for safety evaluation.

    Serious adverse events
    		 TD patients NTD patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 39 (10.26%)
    1 / 24 (4.17%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Epiploic appendagitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 TD patients NTD patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 39 (76.92%)
    20 / 24 (83.33%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Prehypertension
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Fatigue
         subjects affected / exposed
    3 / 39 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    5
    3
    Infusion site erythema
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    Injection site hematoma
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Injection site atrophy
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Injection site erythema
         subjects affected / exposed
    6 / 39 (15.38%)
    1 / 24 (4.17%)
         occurrences all number
    23
    2
    Injection site macule
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    Injection site pain
         subjects affected / exposed
    4 / 39 (10.26%)
    4 / 24 (16.67%)
         occurrences all number
    31
    16
    Injection site papule
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Injection site plaque
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    7
    0
    Injection site pruritus
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    5
    0
    Injection site reaction
         subjects affected / exposed
    2 / 39 (5.13%)
    4 / 24 (16.67%)
         occurrences all number
    4
    6
    Injection site swelling
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Injection site urticaria
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    3 / 39 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    Vessel Puncture Site Thrombosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Injection site hypersensitivity
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Menorrhagia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Pharyngeal erythema
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Blood folate decreased
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    White blood cell count decreased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Contusion
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Post procedural fever
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    4
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 39 (12.82%)
    2 / 24 (8.33%)
         occurrences all number
    8
    3
    Lethargy
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Somnolence
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Syncope
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Migraine
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Anaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Dental caries
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Dyspepsia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Gastroesophageal reflux disease
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    1
    2
    Loose tooth
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Jaundice
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    Rash
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Skin hypopigmentation
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Skin ulcer
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Stasis dermatitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Rash papular
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Bone infarction
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Bone pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Infections and infestations
    Bacterial vaginosis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Bone abscess
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Bronchitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Injection site infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 39 (12.82%)
    3 / 24 (12.50%)
         occurrences all number
    7
    3
    Urinary tract infection
         subjects affected / exposed
    3 / 39 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    5
    2
    Periodontitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Tuberculosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hyperkalemia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Decreased appetite
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Feb 2020
    1) Study endpoints were changed to align with the PTG-300-02 study endpoints. 2) The maximum PTG-300 total dose allowed was changed from 80 mg/weekly to 40 mg/twice per week as preliminary pharmacodynamic data supported twice weekly dosing and longer corresponding reduction in serum iron levels. 3) Section 7.2: Table 4 was revised, Dose Titration was clarified, Dose Titration Algorithm table (Table B) was revised to correct errors and changes were made to specify that patients that do not meet maintenance phase criteria may start maintenance phase on Day 168 to assess effects of PTG-300 on liver and cardiac iron content to allow assessment of iron overload in patients who do not meet criteria for response. 4) Section 7.3: language was added to clarify that female patients becoming pregnant would be withdrawn from the study and clarified follow-up on Day 672 for patients who meet stopping criteria. 5) Study Procedures: Langauge revised. 6) Number of patients was changed to reflect a maximum 192 patients able to enroll in the study. 7) Hydroxyurea was removed from Prohibited Medications. 8) Dose and Mode of Administration was revised was revised to include twice weekly dosing and new dose levels and removal of every 2-week dosing regimen. 9) Efficacy Endpoint added to assess change in pre-treatment baseline of cardiac iron added due to preliminary data suggesting PTG-300 decreases iron overload. 10) Sections 7.2, 7.4, and 10.6: Assessments for cardiac iron added. 11) General changes to Schedule of Assessment Table for NTD and TD patients 12) Section 5: Text revised to reflect required participation in PTG-300-02 prior to participation in PTG-300-03 study. 13) Text added to reflect twice weekly dosing for 40 mg dose. 14) Section 10.3: Corrected CTCAE version from 4.0 to 5.0 for physical examination; Removed fasting requirement from safety laboratory tests. 15) Revised text to provide more detail and justification for sample size

    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 analysis of responders has been combined for study PTG-300-02 and PTG-300-03. Therefore, data for study PTG-300-03 has been reported for the 63 patients who enrolled in study PTG-300-02, instead of the 34 patients who enrolled in PTG-300-03.
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    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.

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