Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
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. |
From Day 0 up to Day 182 |
|
| Primary |
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. |
From Day 183 up to Day 196 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
|
| Secondary |
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab |
The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen. |
Predose on Days 0, 84, and 140 and postdose on Day 182 |
|
| Secondary |
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. |
Predose on Days 0, 84, and 140 and postdose on Day 182 |
|
| Secondary |
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. |
Predose on Days 0, 84, and 140 and postdose on Day 182 |
|
| Secondary |
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. |
Baseline (Day 0) up to end of treatment period (Day 182) |
|
| Secondary |
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. |
Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168 |
|
| Secondary |
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. |
From Day 0 up to Day 196 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
|
| Secondary |
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. |
From Day 0 up to Day 182 |
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