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    Clinical Trial Results:
    HELP Study ExtensionTM: An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of DX-2930 for Prevention Against Acute Attacks of Hereditary Angioedema (HAE)

    Summary
    EudraCT number
    2015-005255-27
    Trial protocol
    GB   DE   IT  
    Global end of trial date
    31 Oct 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    09 May 2020
    First version publication date
    09 May 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    DX-2930-04
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02741596
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    IND: 116647
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, United States, MA 02421
    Public contact
    Study Director, Shire, 1 866-842-5335, ClinicalTransparency@shire.com
    Scientific contact
    Study Director, Shire, 1 866-842-5335, ClinicalTransparency@shire.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001864-PIP01-15
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Oct 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to evaluate the long-term safety of repeated subcutaneous (SC) administrations of lanadelumab (DX-2930).
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation of Good Clinical Practice, the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    26 May 2016
    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 States: 147
    Country: Number of subjects enrolled
    Jordan: 13
    Country: Number of subjects enrolled
    Canada: 13
    Country: Number of subjects enrolled
    European Union: 39
    Worldwide total number of subjects
    212
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    21
    Adults (18-64 years)
    180
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 43 sites across United States, Canada, Europe and Jorden between 26 May 2016 (first subject first visit) and 31 October 2019 (last subject last visit).

    Pre-assignment
    Screening details
    A total of 212 subjects were enrolled and received treatment in two groups (Rollover subjects [109] and Non-rollover subjects [103]). Subjects who rolled from the DX-2930-03 (2015-005255-27) study were in Rollover group and subjects who were directly enrolled into this DX-2930-04 study were in Non-rollover group.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Rollover Subjects
    Arm description
    Subjects who rolled from the DX-2930-03 (2015-005255-27) study received 300 milligrams (mg) of DX-2930 subcutaneous (SC) injection on Day 0 followed by a second dose after subjects reported their first HAE attack and continued to receive repeated SC administrations of 300 mg DX-2930 every 2 weeks (q2wks) throughout the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days were required between subsequent administrations.
    Arm type
    Experimental

    Investigational medicinal product name
    Lanadelumab
    Investigational medicinal product code
    DX-2930
    Other name
    SHP643
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection DX-2930 for q2wks up to 924 days.

    Arm title
    Non-rollover Subjects
    Arm description
    Subjects who directly entered in to this DX-2930-04 study received 300 mg of DX-2930 SC injection on Day 0 and continued to receive SC administrations of 300 mg DX-2930 every 2 weeks throughout the treatment period (up to 924 days).
    Arm type
    Experimental

    Investigational medicinal product name
    Lanadelumab
    Investigational medicinal product code
    DX-2930
    Other name
    SHP643
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection DX-2930 for q2wks up to 924 days.

    Number of subjects in period 1
    Rollover Subjects Non-rollover Subjects
    Started
    109
    103
    Completed
    31
    25
    Not completed
    78
    78
         Physician decision
    2
    1
         Adverse event
    1
    5
         Pregnancy
    3
    1
         Subject withdrawn - Other
    17
    4
         Subject withdrawn - to commercial product
    54
    63
         Unspecified
    -
    3
         Lost to follow-up
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rollover Subjects
    Reporting group description
    Subjects who rolled from the DX-2930-03 (2015-005255-27) study received 300 milligrams (mg) of DX-2930 subcutaneous (SC) injection on Day 0 followed by a second dose after subjects reported their first HAE attack and continued to receive repeated SC administrations of 300 mg DX-2930 every 2 weeks (q2wks) throughout the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days were required between subsequent administrations.

    Reporting group title
    Non-rollover Subjects
    Reporting group description
    Subjects who directly entered in to this DX-2930-04 study received 300 mg of DX-2930 SC injection on Day 0 and continued to receive SC administrations of 300 mg DX-2930 every 2 weeks throughout the treatment period (up to 924 days).

    Reporting group values
    Rollover Subjects Non-rollover Subjects Total
    Number of subjects
    109 103
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    41.9 ± 14.74 39.5 ± 16.71 -
    Gender categorical
    Units: Subjects
        Female
    75 68 143
        Male
    34 35 69
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    2 0 2
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    8 2 10
        White
    99 99 198
        More than one race
    0 1 1
        Unknown or Not Reported
    0 1 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    8 5 13
        Not Hispanic or Latino
    101 97 198
        Unknown or Not Reported
    0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Rollover Subjects
    Reporting group description
    Subjects who rolled from the DX-2930-03 (2015-005255-27) study received 300 milligrams (mg) of DX-2930 subcutaneous (SC) injection on Day 0 followed by a second dose after subjects reported their first HAE attack and continued to receive repeated SC administrations of 300 mg DX-2930 every 2 weeks (q2wks) throughout the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days were required between subsequent administrations.

    Reporting group title
    Non-rollover Subjects
    Reporting group description
    Subjects who directly entered in to this DX-2930-04 study received 300 mg of DX-2930 SC injection on Day 0 and continued to receive SC administrations of 300 mg DX-2930 every 2 weeks throughout the treatment period (up to 924 days).

    Primary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    An adverse event (AE) was any untoward medical occurrence in a clinical trial subject whether or not it appeared to had a causal relationship with the treatment administered. Treatment-emergent AEs are defined as AEs with onset at the time of or following the first exposure to open-label DX-2930 in this study, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment.
    End point type
    Primary
    End point timeframe
    From start of the study up to follow-up (Day 952)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical testing was performed for the primary end point.
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    109
    103
    Units: Subjects
        Subjects with any TEAE
    105
    101
    No statistical analyses for this end point

    Secondary: Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During the Treatment Period

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    End point title
    Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During the Treatment Period
    End point description
    HAE attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. The treatment period investigator-confirmed HAE attack rate was calculated for each subject as the number of investigator-confirmed HAE attacks occurring during the treatment period (regular dosing stage of the treatment period for rollover subjects) divided by the number of days the subject contributed to the treatment period multiplied by 28 days. Rate of investigator-confirmed HAE attacks during the treatment period was reported. Safety population was analysed, which included all subjects who received any study drug after entering the DX-2930-04 study. Here, the number of subjects analyzed signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 924
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    106
    103
    Units: Attacks per month
        arithmetic mean (standard deviation)
    0.27 ± 0.581
    0.22 ± 0.521
    No statistical analyses for this end point

    Secondary: Rate of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During the Treatment Period

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    End point title
    Rate of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During the Treatment Period
    End point description
    HAE attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. Rate of investigator-confirmed HAE attacks requiring acute treatment for each subject as the number of investigator-confirmed HAE attacks occurring during the treatment period (regular dosing stage of the treatment period for rollover subjects) divided by the number of days the subject contributed to the treatment period multiplied by 28 days. Safety population was analysed, which included all subjects who received any study drug after entering the DX-2930-04 study. Here, the number of subjects analyzed signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 924
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    106
    103
    Units: Attacks per month
        arithmetic mean (standard deviation)
    0.20 ± 0.430
    0.21 ± 0.517
    No statistical analyses for this end point

    Secondary: Rate of Moderate or Severe Hereditary Angioedema (HAE) Attacks During the Treatment Period

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    End point title
    Rate of Moderate or Severe Hereditary Angioedema (HAE) Attacks During the Treatment Period
    End point description
    HAE attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. Moderate and severe investigator-confirmed HAE attacks were the attacks that were moderate or severe as per the HAE attack assessment and reporting procedures (HAARP) defined severity. The overall severity of attack was determined by the investigator using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Safety population was analysed, which included all subjects who received any study drug after entering the DX-2930-04 study. Here, the number of subjects analysed signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 924
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    106
    103
    Units: Attacks per month
        arithmetic mean (standard deviation)
    0.21 ± 0.479
    0.19 ± 0.512
    No statistical analyses for this end point

    Secondary: Rate of High-Morbidity Hereditary Angioedema (HAE) Attacks During the Treatment Period

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    End point title
    Rate of High-Morbidity Hereditary Angioedema (HAE) Attacks During the Treatment Period
    End point description
    HAE attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. High-morbidity Hereditary Angioedema (HAE) attack was defined as any attack that had at least one of the following characteristics: severe, resulted in hospitalization (except hospitalization for observation lesser than [<] 24 hours), hemodynamically significant (systolic blood pressure <90 millimetre of mercury [mmHg], required intravenous hydration, or associated with syncope or near-syncope) or laryngeal edema. Number of high-morbidity HAE attacks during the treatment period was analysed and reported using the methods for the overall number of investigator-confirmed HAE attacks with the exception of the monthly line graphs. Safety population was analysed, which included all subjects who received any study drug after entering the DX-2930-04 study. Here the number of subjects analysed signifies subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 924
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    106
    103
    Units: Attacks per month
        arithmetic mean (standard deviation)
    0.03 ± 0.085
    0.04 ± 0.103
    No statistical analyses for this end point

    Secondary: Time to First Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During in Rollover Subjects

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    End point title
    Time to First Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During in Rollover Subjects
    End point description
    HAE attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. Time to first investigator-confirmed HAE attack was calculated from the time of first open-label dose to the start time of the first investigator-confirmed HAE attack. Time to the first investigator-confirmed HAE attack was analysed and reported only in rollover safety population. Rollover Safety Population was analysed, which included subset of subjects who participated in the DX-2930-03 (2015-005255-27) study and received any study drug after entering the DX-2930-04 study (that is any exposure to open-label DX-2930).
    End point type
    Secondary
    End point timeframe
    Up to Day 924
    End point values
    Rollover Subjects Non-rollover Subjects
    Number of subjects analysed
    109
    0 [2]
    Units: Days
        median (inter-quartile range (Q1-Q3))
    43 (18 to 97)
    ( to )
    Notes
    [2] - End point was planned only for rollover subjects. hence, non-rollover subjects were not evaluated.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug administration up to follow-up (Day 952)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Rollover Subjects
    Reporting group description
    Subjects who rolled from the DX-2930-03 (2015-005255-27) study received 300 milligrams (mg) of DX-2930 subcutaneous (SC) injection on Day 0 followed by a second dose after subjects reported their first HAE attack and continued to receive repeated SC administrations of 300 mg DX-2930 every 2 weeks (q2wks) throughout the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days were required between subsequent administrations.

    Reporting group title
    Non-Rollover Subjects
    Reporting group description
    Subjects who directly entered in to this DX-2930-04 study received 300 mg of DX-2930 SC injection on Day 0 and continued to receive SC administrations of 300 mg DX-2930 every 2 weeks throughout the treatment period (up to 924 days).

    Serious adverse events
    Rollover Subjects Non-Rollover Subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 109 (11.01%)
    9 / 103 (8.74%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Lymphoedema
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Fibrosarcoma
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental exposure to product
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site inflammation
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery stenosis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Hypochromic anaemia
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fissure
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Breast abscess
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Rollover Subjects Non-Rollover Subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    100 / 109 (91.74%)
    96 / 103 (93.20%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    8 / 109 (7.34%)
    4 / 103 (3.88%)
         occurrences all number
    9
    4
    Fall
         subjects affected / exposed
    6 / 109 (5.50%)
    3 / 103 (2.91%)
         occurrences all number
    6
    3
    Ligament sprain
         subjects affected / exposed
    6 / 109 (5.50%)
    12 / 103 (11.65%)
         occurrences all number
    7
    14
    Procedural pain
         subjects affected / exposed
    7 / 109 (6.42%)
    4 / 103 (3.88%)
         occurrences all number
    9
    5
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 109 (3.67%)
    6 / 103 (5.83%)
         occurrences all number
    9
    7
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 109 (0.92%)
    6 / 103 (5.83%)
         occurrences all number
    3
    8
    Blood creatine phosphokinase increased
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 103 (4.85%)
         occurrences all number
    8
    8
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    6 / 109 (5.50%)
    2 / 103 (1.94%)
         occurrences all number
    6
    3
    Cough
         subjects affected / exposed
    7 / 109 (6.42%)
    7 / 103 (6.80%)
         occurrences all number
    7
    8
    Nasal congestion
         subjects affected / exposed
    7 / 109 (6.42%)
    2 / 103 (1.94%)
         occurrences all number
    7
    2
    Oropharyngeal pain
         subjects affected / exposed
    8 / 109 (7.34%)
    8 / 103 (7.77%)
         occurrences all number
    9
    9
    Nervous system disorders
    Headache
         subjects affected / exposed
    29 / 109 (26.61%)
    23 / 103 (22.33%)
         occurrences all number
    70
    37
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    10 / 109 (9.17%)
    10 / 103 (9.71%)
         occurrences all number
    15
    12
    Injection site bruising
         subjects affected / exposed
    13 / 109 (11.93%)
    13 / 103 (12.62%)
         occurrences all number
    21
    72
    Injection site erythema
         subjects affected / exposed
    16 / 109 (14.68%)
    20 / 103 (19.42%)
         occurrences all number
    40
    103
    Injection site pain
         subjects affected / exposed
    45 / 109 (41.28%)
    55 / 103 (53.40%)
         occurrences all number
    737
    994
    Injection site pruritus
         subjects affected / exposed
    4 / 109 (3.67%)
    6 / 103 (5.83%)
         occurrences all number
    5
    14
    Injection site swelling
         subjects affected / exposed
    6 / 109 (5.50%)
    11 / 103 (10.68%)
         occurrences all number
    49
    26
    Peripheral swelling
         subjects affected / exposed
    7 / 109 (6.42%)
    1 / 103 (0.97%)
         occurrences all number
    11
    1
    Pyrexia
         subjects affected / exposed
    3 / 109 (2.75%)
    8 / 103 (7.77%)
         occurrences all number
    4
    8
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    8 / 109 (7.34%)
    5 / 103 (4.85%)
         occurrences all number
    9
    5
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 109 (1.83%)
    6 / 103 (5.83%)
         occurrences all number
    2
    6
    Abdominal pain
         subjects affected / exposed
    11 / 109 (10.09%)
    11 / 103 (10.68%)
         occurrences all number
    13
    12
    Abdominal pain upper
         subjects affected / exposed
    4 / 109 (3.67%)
    7 / 103 (6.80%)
         occurrences all number
    4
    7
    Constipation
         subjects affected / exposed
    6 / 109 (5.50%)
    4 / 103 (3.88%)
         occurrences all number
    6
    4
    Diarrhoea
         subjects affected / exposed
    13 / 109 (11.93%)
    10 / 103 (9.71%)
         occurrences all number
    16
    11
    Dyspepsia
         subjects affected / exposed
    8 / 109 (7.34%)
    3 / 103 (2.91%)
         occurrences all number
    8
    3
    Nausea
         subjects affected / exposed
    13 / 109 (11.93%)
    9 / 103 (8.74%)
         occurrences all number
    16
    14
    Toothache
         subjects affected / exposed
    6 / 109 (5.50%)
    5 / 103 (4.85%)
         occurrences all number
    9
    6
    Vomiting
         subjects affected / exposed
    7 / 109 (6.42%)
    4 / 103 (3.88%)
         occurrences all number
    8
    4
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    7 / 109 (6.42%)
    3 / 103 (2.91%)
         occurrences all number
    7
    3
    Pruritus
         subjects affected / exposed
    6 / 109 (5.50%)
    1 / 103 (0.97%)
         occurrences all number
    7
    1
    Rash
         subjects affected / exposed
    8 / 109 (7.34%)
    5 / 103 (4.85%)
         occurrences all number
    8
    5
    Urticaria
         subjects affected / exposed
    7 / 109 (6.42%)
    3 / 103 (2.91%)
         occurrences all number
    8
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 109 (10.09%)
    16 / 103 (15.53%)
         occurrences all number
    20
    17
    Back pain
         subjects affected / exposed
    16 / 109 (14.68%)
    10 / 103 (9.71%)
         occurrences all number
    29
    12
    Musculoskeletal pain
         subjects affected / exposed
    8 / 109 (7.34%)
    9 / 103 (8.74%)
         occurrences all number
    8
    10
    Myalgia
         subjects affected / exposed
    7 / 109 (6.42%)
    3 / 103 (2.91%)
         occurrences all number
    10
    5
    Pain in extremity
         subjects affected / exposed
    12 / 109 (11.01%)
    9 / 103 (8.74%)
         occurrences all number
    13
    12
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    7 / 109 (6.42%)
    7 / 103 (6.80%)
         occurrences all number
    10
    11
    Bronchitis
         subjects affected / exposed
    5 / 109 (4.59%)
    8 / 103 (7.77%)
         occurrences all number
    7
    10
    Gastroenteritis
         subjects affected / exposed
    4 / 109 (3.67%)
    11 / 103 (10.68%)
         occurrences all number
    5
    14
    Gastroenteritis viral
         subjects affected / exposed
    5 / 109 (4.59%)
    10 / 103 (9.71%)
         occurrences all number
    5
    11
    Gastrointestinal infection
         subjects affected / exposed
    6 / 109 (5.50%)
    4 / 103 (3.88%)
         occurrences all number
    7
    4
    Influenza
         subjects affected / exposed
    13 / 109 (11.93%)
    9 / 103 (8.74%)
         occurrences all number
    17
    10
    Otitis media
         subjects affected / exposed
    6 / 109 (5.50%)
    4 / 103 (3.88%)
         occurrences all number
    7
    4
    Pharyngitis streptococcal
         subjects affected / exposed
    3 / 109 (2.75%)
    6 / 103 (5.83%)
         occurrences all number
    3
    8
    Sinusitis
         subjects affected / exposed
    13 / 109 (11.93%)
    10 / 103 (9.71%)
         occurrences all number
    13
    11
    Upper respiratory tract infection
         subjects affected / exposed
    30 / 109 (27.52%)
    25 / 103 (24.27%)
         occurrences all number
    51
    54
    Urinary tract infection
         subjects affected / exposed
    10 / 109 (9.17%)
    13 / 103 (12.62%)
         occurrences all number
    12
    21
    Viral upper respiratory tract infection
         subjects affected / exposed
    51 / 109 (46.79%)
    38 / 103 (36.89%)
         occurrences all number
    119
    87

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2016
    The tertiary objective to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) profile of lanadelumab was clarified to indicate administration would be SC. Three additional tertiary objectives were added to obtain more comprehensive information: * To evaluate safety and efficacy in the non-rollover population of switching from from long-term prophylactic (LTP) treatment to lanadelumab * To evaluate breakthrough attack characteristics while receiving lanadelumab compared to historical baseline * To evaluate subject experience with self-administration of lanadelumab including ease of SC administration of lanadelum The number of non-rollover subjects was increased from at least 50 subjects up to a maximum of 100 subjects. Enrollment of subjects 12 to 17 years age was revised to be at least 15 including the estimated 10 rollover subjects from Study DX-2930-03 (2015-005255-27). Therefore, the total enrollment for the study was updated to be at least 150, but not more than 250. The study was extended in duration from 6 months to approximately 1 year and subsequently the number of doses of study drug a subject could receive was increased. Study Activities Schedule was revised to accommodate study assessments at dosing Visits 14 through 26. Follow-up visits (following end of treatment) are now occurring at Days 264, 378, and 392 (Visits 27, 28, and 29). Efficacy endpoints were revised from mean rates to number of attacks. The study was extended in duration from 6 months to approximately 1 year and subsequently the number of doses of study drug a subject could receive was increased. Efficacy endpoints were revised from mean rates to number of attacks. The efficacy evaluation period was updated to begin at Day 0 instead of Day 14 to be consistent with the intent-to-treat analysis principle.
    20 Jan 2017
    Clarified that subjects in Study DX-2930-03 (2015-005255-27) can be consented for enrollment in Study DX-2930-04 on or after Day 168 of Study DX-2930-03 (2015-005255-27). Removed remnant text regarding the requirement to complete a 2-week washout period before entering the treatment period for non-rollover subjects on LTP for HAE. Washout period does not exist for non-rollover subjects. Removed safety analysis category called “pretreatment group” since a pretreatment period does not exist in this study.
    29 Jun 2017
    A new tertiary objective and related measurement have been added to evaluate exploratory biomarker(s) of angioedema disease-state bioactivity in blood. Additional biomarker assessments have been added to the study to evaluate the effect of lanadelumab on disease activity. A new tertiary efficacy objective and related measurement have been added to better understand the clinical response to rescue medications while on lanadelumab therapy. * Objective: To assess the clinical response of rescue medications for the treatment of acute angioedema attacks while on lanadelumab therapy (applicable for subjects >= 18 years of age) * Measurement: Subject response to rescue medications. A new tertiary objective was added to assess subjects’ satisfaction with lanadelumab. * Objective: To assess treatment satisfaction * Measurement: Treatment satisfaction was to be measured using the Treatment Satisfaction Questionnaire for Medication (TSQM-9). The TSQM-9 was to be a 9-item validated instrument. The treatment period was extended from 12 to up to 30 months to accommodate the additional changes to the study described above. The requirement that each attack be confirmed by the investigator within 72 hours for non-serious AE attacks was expanded to 7 calendar days. Note: This refers only to confirmation of attacks, not reporting of serious adverse events (SAEs) or AEs. Electrocardiogram (ECG) were to be assessed through Day 364, at the end of the study, and when clinically required. The following subgroup analysis was added to the statistical section for consistency with statistical analysis used in Study DX-2930-03 (2015-005255-27): “History of laryngeal HAE attacks (history of laryngeal attack, no history of laryngeal attack).”

    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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