CClinicalTrials.gg
CompletedNCT04444895Updated Jun 17, 2024Results posted

A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor

A Phase 3 interventional study of Lanadelumab in Angioedema, sponsored by Shire. Completed at 35 sites in 10 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2024-06-17.

Sponsored by Shire · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
73
Allocation
Not applicable
Ages
12 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the long-term safety and efficacy of repeated subcutaneous (SC) administration of lanadelumab in adolescents and adults with non-histaminergic angioedema with normal C1-inhibitor who completed study SHP643-303 (NCT04206605).

Read the detailed description

This study consists of 26-week treatment period (Day 0 to Day 182) and a 2-week follow-up period. Participants who completed the double-blind treatment period at Day 182 of Study SHP643-303 (NCT04206605) will enroll into this extension study.

02

Conditions studied

03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Males and females, 12 years of age and older diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303 (NCT04206605).
  • Participants must have completed the treatment period (through Visit 26/Day 182) of Study SHP643-303 (NCT04206605) without reporting a clinically significant TEAE that would preclude subsequent exposure to lanadelumab.
  • Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
  • Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study; or females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
  • The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research ethics board/ethics committee (IRB/REB/EC) at any time prior to study start. If the participant is a minor (i.e. lesser then (\<) 18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (i.e. permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.

Exclusion criteria

Exclusion Criteria:

  • Discontinued from Study SHP643-303 (NCT04206605) after enrollment but before Visit 26 for any reason.
  • Presence of important safety concerns identified in Study SHP643-303 (NCT04206605) that would preclude participation in this study.
  • Dosing with an investigational product (IP, not including IP defined in antecedent Study SHP643-303 [NCT04206605]) or exposure to an investigational device within 4 weeks prior to Day 0.
  • Participants has a known hypersensitivity to the investigational product or its components.
  • Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
73 participants (actual)

Study arms

  • Experimental
    Lanadelumab 300 mg Every 2 Weeks

    Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.

    Drug: Lanadelumab

Interventions

  • DrugLanadelumab

    Lanadelumab SC injection

    Also known as: DX-2930, SHP643, TAK-743

05

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period

    TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

    Time frame: From Day 0 up to Day 182

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up

    TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

    Time frame: From Day 183 up to Day 196

Secondary outcomes

  1. Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

    An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

    Time frame: From Day 0 up to Day 182

  2. Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

    The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

    Time frame: From Day 0 up to Day 182

  3. Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

    A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic blood pressure (BP) \<90 millimetres of mercury (mmHg), requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal.

    Time frame: From Day 0 up to Day 182

  4. Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

    The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

    Time frame: Predose on Days 0, 84, and 140 and postdose on Day 182

  5. Plasma Kallikrein (pKal) Activity

    Plasma kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) with factor XIIa activation level to assess the pharmacodynamics of lanadelumab. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

    Time frame: Predose on Days 0, 84, and 140 and postdose on Day 182

  6. Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma

    Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma was assessed. As pre-specified in the statistical analysis plan (SAP), data for this outcome measure was collected and analyzed as a single group irrespective of dosing regimen.

    Time frame: Predose on Days 0, 84, and 140 and postdose on Day 182

  7. Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period

    The AE-QoL questionnaire is self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema(including hereditary angioedema\[HAE\]). It consists of 17 disease-specific QOL items, to produce total AE-QoL score \& 4 domain scores(functioning,fatigue/mood,fear/shame,nutrition) each of 17 items had 5-point response scale ranging from 1(Never) to 5(Very Often). It was scored according to developers' guidelines to produce 4 domain scores yielding total score. The raw total score(mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0-100, based on maximum possible score, where higher score, greater QoL impairment. Negative change from Baseline indicates better QoL. Baseline: Last non-missing value prior to first exposure to study drug(based on date or date/time). As pre-specified in SAP, data for this outcome measure was collected and analyzed as single group irrespective of dosing regimen.

    Time frame: Baseline (Day 0) up to end of treatment period (Day 182)

  8. Number of Participants With Any Pause During Injection

    An injection report was completed by the participant (or parent/caregiver) following each dose administration of lanadelumab injection used during the treatment period and any kind of pause during injection was captured. Categories with at least one participant with event are reported.

    Time frame: Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168

  9. Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants Who Switched Dosing Regimen

    TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

    Time frame: From Day 0 up to Day 196

  10. Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

    An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

    Time frame: From Day 0 up to Day 182

  11. Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

    The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

    Time frame: From Day 0 up to Day 182

  12. Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

    A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic BP \<90 mmHg, requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal.

    Time frame: From Day 0 up to Day 182

06

Results

Posted Jun 17, 2024

Participant flow

A total of 73 participants took part in the study at 34 investigative sites in Canada, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Spain, and the United States from 05 February 2021 to 05 May 2023.

Participant flow — Overall Study
MilestoneLanadelumab 300 mg Q2W
Started73
Reduced-dose safety analysisset(rd-sfas)2
Completed64
Not completed9
Withdrew: Adverse event2
Withdrew: Lost to follow-up2
Withdrew: Withdrawal by subject5

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period

TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

Time frame:
From Day 0 up to Day 182
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period
ParticipantsLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Any TEAEs: Non-Angioedema Attack551
Any TEAEs: Angioedema Attack611
AESI: Non-Angioedema Attack10
AESI: Angioedema Attack00
Any SAEs: Non-Angioedema Attack51
Any SAEs: Angioedema Attack30
PrimaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up

TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

Time frame:
From Day 183 up to Day 196
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up
ParticipantsLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Any TEAEs: Non-Angioedema Attack40
Any TEAEs: Angioedema Attack190
AESI: Non-Angioedema Attack00
AESI: Angioedema Attack00
Any SAEs: Non-Angioedema Attack00
Any SAEs: Angioedema Attack00
SecondaryNumber of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 1825952
SecondaryNumber of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 1823912
SecondaryNumber of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic blood pressure (BP) \<90 millimetres of mercury (mmHg), requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 1822321
SecondaryPharmacokinetic (PK) Plasma Concentrations of Lanadelumab

The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Time frame:
Predose on Days 0, 84, and 140 and postdose on Day 182
Reported as:
Mean · nanograms per milliliter (ng/mL)
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
nanograms per milliliter (ng/mL)Lanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Day 014419.068 ± 13208.1952NA ± NA
Day 8417021.002 ± 10116.52797047.860 ± NA
Day 14021138.057 ± 12076.91864944.010 ± NA
Day 18218799.596 ± 12054.110514573.340 ± NA
SecondaryPlasma Kallikrein (pKal) Activity

Plasma kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) with factor XIIa activation level to assess the pharmacodynamics of lanadelumab. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Time frame:
Predose on Days 0, 84, and 140 and postdose on Day 182
Reported as:
Mean · percentage of cHMWK
Plasma Kallikrein (pKal) Activity
percentage of cHMWKLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Day 015.306 ± 15.2413NA ± NA
Day 8417.586 ± 9.243721.600 ± NA
Day 14017.238 ± 9.159044.700 ± NA
Day 18215.515 ± 9.207437.100 ± NA
SecondaryNumber of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma

Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma was assessed. As pre-specified in the statistical analysis plan (SAP), data for this outcome measure was collected and analyzed as a single group irrespective of dosing regimen.

Time frame:
Predose on Days 0, 84, and 140 and postdose on Day 182
Reported as:
Count of participants · Participants
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma
ParticipantsLanadelumab 300 mg Q2W
Day 02
Day 842
Day 1403
Day 1824
SecondaryChange From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period

The AE-QoL questionnaire is self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema(including hereditary angioedema\[HAE\]). It consists of 17 disease-specific QOL items, to produce total AE-QoL score \& 4 domain scores(functioning,fatigue/mood,fear/shame,nutrition) each of 17 items had 5-point response scale ranging from 1(Never) to 5(Very Often). It was scored according to developers' guidelines to produce 4 domain scores yielding total score. The raw total score(mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0-100, based on maximum possible score, where higher score, greater QoL impairment. Negative change from Baseline indicates better QoL. Baseline: Last non-missing value prior to first exposure to study drug(based on date or date/time). As pre-specified in SAP, data for this outcome measure was collected and analyzed as single group irrespective of dosing regimen.

Time frame:
Baseline (Day 0) up to end of treatment period (Day 182)
Reported as:
Mean · score on a scale
Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period
score on a scaleLanadelumab 300 mg Q2W
Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period-12.73 ± 20.696
SecondaryNumber of Participants With Any Pause During Injection

An injection report was completed by the participant (or parent/caregiver) following each dose administration of lanadelumab injection used during the treatment period and any kind of pause during injection was captured. Categories with at least one participant with event are reported.

Time frame:
Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168
Reported as:
Count of participants · Participants
Number of Participants With Any Pause During Injection
ParticipantsLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Day 030
Day 1450
Day 2850
Day 4230
Day 5630
Day 7040
Day 8440
Day 9810
Day 11221
Day 12620
Day 14030
Day 15420
Day 16810
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants Who Switched Dosing Regimen

TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

Time frame:
From Day 0 up to Day 196
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants Who Switched Dosing Regimen
ParticipantsLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Any TEAEs: Non-Angioedema Attack21
Any TEAEs: Angioedema Attack01
AESI: Non-Angioedema Attack00
AESI: Angioedema Attack00
Any SAEs: Non-Angioedema Attack01
Any SAEs: Angioedema Attack00
SecondaryNumber of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen02
SecondaryNumber of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen02
SecondaryNumber of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen

A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic BP \<90 mmHg, requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal.

Time frame:
From Day 0 up to Day 182
Reported as:
Number · angioedema attacks
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
angioedema attacksLanadelumab 300 mg Q2WLanadelumab 300 mg Q4W
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen01

Adverse events

Collected over From the first study drug administration up to follow-up (Day 196). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lanadelumab 300 mg Every 2 Weeks0/73 (0%)7/73 (9.6%)65/73 (89%)
Lanadelumab 300 mg Every 4 Weeks0/2 (0%)1/2 (50%)1/2 (50%)
Most frequent serious events
Most frequent serious events
EventLanadelumab 300 mg Every 2 WeeksLanadelumab 300 mg Every 4 Weeks
Abdominal pain upperGastrointestinal disorders0/731/2
AngioedemaSkin and subcutaneous tissue disorders3/730/2
Acute myocardial infarctionCardiac disorders1/730/2
Arthritis viralInfections and infestations1/730/2
CellulitisInfections and infestations1/730/2
Deep vein thrombosisVascular disorders1/730/2
Device related sepsisInfections and infestations1/730/2
Lactic acidosisMetabolism and nutrition disorders1/730/2
Suicide attemptPsychiatric disorders1/730/2
Most frequent other events
Showing 10 of 12
Most frequent other events
EventLanadelumab 300 mg Every 2 WeeksLanadelumab 300 mg Every 4 Weeks
AngioedemaSkin and subcutaneous tissue disorders61/731/2
Eye swellingEye disorders0/731/2
FatigueGeneral disorders1/731/2
HeadacheNervous system disorders10/731/2
MalaiseGeneral disorders1/731/2
COVID-19Infections and infestations17/730/2
Injection site painGeneral disorders8/730/2
ArthralgiaMusculoskeletal and connective tissue disorders7/730/2
NauseaGastrointestinal disorders6/730/2
Upper respiratory tract infectionInfections and infestations6/730/2

Baseline characteristics

The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab).

Age, Continuous
Age, Continuous(years)Lanadelumab 300 mg Q2W
Mean43.7 ± 12.63
Sex: Female, Male
Sex: Female, Male(Participants)Lanadelumab 300 mg Q2W
Female59
Male14
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Lanadelumab 300 mg Q2W
Hispanic or Latino9
Not Hispanic or Latino63
Unknown or Not Reported1
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Lanadelumab 300 mg Q2W
American Indian or Alaska Native0
Asian4
Native Hawaiian or Other Pacific Islander0
Black or African American4
White64
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(Participants)Lanadelumab 300 mg Q2W
Canada5
France1
Germany3
Hungary2
Italy7
Japan4
Netherlands3
Poland6
Spain3
United States39
Weight
Weight(kilograms (kg))Lanadelumab 300 mg Q2W
Mean81.52 ± 23.129
Height
Height(centimeters (cm))Lanadelumab 300 mg Q2W
Mean166.75 ± 8.938
Body Mass Index (BMI)
Body Mass Index (BMI)(kilogram per square meter (kg/m^2))Lanadelumab 300 mg Q2W
Mean29.23 ± 7.972
07

Study locations

35 sites
  • Clinical Research Center of Alabama
    Birmingham, Alabama 35209, United States
  • Medical Research of Arizona
    Scottsdale, Arizona 85248, United States
  • UCSD Angioedema Center
    San Diego, California 92122, United States
  • Allergy and Asthma Clinical Research Inc
    Walnut Creek, California 94598, United States
  • Asthma and Allergy Associates, PC
    Colorado Springs, Colorado 80907, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • Kanarek Allergy, Asthma and Immunology
    Overland Park, Kansas 66211, United States
  • Institute for Asthma & Allergy, P.C.
    Chevy Chase, Maryland 20815, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University of Michigan
    Ann Arbor, Michigan 48106, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Washington University
    Saint Louis, Missouri 63141, United States
  • Bernstein Clinical Research Center, LLC
    Cincinnati, Ohio 45236, United States
  • Optimed Research, LTD
    Columbus, Ohio 43235, United States
  • Seattle Allergy & Asthma Research Institute
    Seattle, Washington 98115, United States
  • Ottawa Allergy Research Corporation
    Ottawa, Ontario K1H 1E4, Canada
  • Clinique Specialisee en Allergie de la Capitale
    Québec, Quebec G1V 4W2, Canada
  • Hôpital Saint-Antoine
    Paris, 75012, France
  • Klinikum rechts der Isar der TU
    Muenchen, Bayern 81675, Germany
  • Klinikum der Johann Wolfgang Goethe-Universitaet pt
    Frankfurt, Hessen 60590, Germany
  • Semmelweis Egyetem
    Budapest, 1088, Hungary
  • A.O. Ospedali riuniti Villa Sofia - Cervello,
    Palermo, Palermo Palermo 90100, Italy
  • Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
    Milano, 20157, Italy
  • Azienda Ospedaliera Universitaria "Federico II"
    Napoli, 80131, Italy
  • Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
    Salerno, 84131, Italy
  • Hiroshima University Hospital
    Hiroshima-shi, Hiroshima-Ken 734-8551, Japan
  • Kobe University Hospital
    Kobe-shi, Hyogo-Ken 650-0017, Japan
  • Clover Hospital
    Fujisawa-shi, Kanagawa-Ken 251-0025, Japan
  • Amsterdam UMC
    Amsterdam, 1105 AZ, Netherlands
  • Universitair Medisch Centrum Groningen
    Groningen, 9713 GZ, Netherlands
  • UMC Utrecht
    Utrecht, 3508 GA, Netherlands
  • NZOZ Homeo Medicus, Poradnia Alergologiczna
    Bialystok, 15-867, Poland
  • "ALL-MED" Specjalistyczna Opieka Medyczna Filia
    Wroclaw, 53-201, Poland
  • Hospital Universitario Cruces
    Barakaldo, Vizcaya 48903, Spain
  • Hospital Universitari Vall d'Hebron
    Barcelona, 08035, Spain
08

References and documents

Study documents

  • Study protocol · Sep 14, 2020
  • Statistical analysis plan · Jun 29, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT04444895
Lead sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.
Responsible party
Sponsor
First posted
Jun 24, 2020
Start date
Feb 5, 2021
Primary completion
May 5, 2023
Completion
May 5, 2023
Results posted
Jun 17, 2024
Last update
Jun 17, 2024

Study contacts

Study Director
study director · Takeda Development Center Americas

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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