Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
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). Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. |
Day 0 through Day 182 |
|
Secondary |
Number of Participants Achieving Attack-Free Status 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the treatment period of day 0 through day 182 was assessed. |
Day 0 through Day 182 |
|
Secondary |
Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 |
Angioedema attack was defined as symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, 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 tongue, palate, uvula, or larynx). Overall severity of the participant's angioedema attack was determined by site using the following definitions: 1. Mild: Transient or mild discomfort; 2. Moderate: Mild to moderate limitation in activity some assistance needed; 3. Severe: Marked limitation in activity, assistance required. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by number of days the participant contributed to the specified period multiplied by 28 days. |
Day 0 Through Day 182 |
|
Secondary |
Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 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 presumed steady state period of day 70 through day 182 were assessed. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. |
Day 70 through Day 182 |
|
Secondary |
Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the presumed steady state period of day 70 through day 182 was assessed. |
Day 70 through Day 182 |
|
Secondary |
Number of Participants With Maximum Attack Severity During 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 participants with maximum attack severity during treatment period of day 0 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. |
Day 0 through Day 182 |
|
Secondary |
Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Presumed Steady State Period of Day 70 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). Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of investigator-confirmed moderate or severe angioedema attacks during the presumed steady state period of day 70 through day 182 were assessed. |
Day 70 through Day 182 |
|
Secondary |
Number of Participants With Maximum Attack Severity During Presumed Steady State Period of Day 70 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 participants with maximum attack severity during the presumed steady state period of day 70 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. |
Day 70 through Day 182 |
|
Secondary |
Time to First Angioedema Attack After Day 0 Through Day 182 |
The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 0 through Day 182 was calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 0 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 0 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. |
Day 0 Through Day 182 |
|
Secondary |
Time to First Angioedema Attack After Day 70 Through Day 182 |
The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 70 through Day 182 was calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 70 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 70 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. |
Day 70 through Day 182 |
|
Secondary |
Number of Participants Achieving at Least 50 %, 70%, 90% and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks During Each of the Efficacy Evaluation Periods Relative to the Observation Period NNA |
The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema attack rate. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of participants achieving at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks per 4 weeks during each of the efficacy evaluation periods relative to the observation period NNA was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. |
Day 0 Through Day 182 |
|
Secondary |
Number of Participants Achieving Normalized Number of Attacks (NNA) Less Than (<)1.0 Per 4 Weeks During Each of the Efficacy Evaluation Periods |
The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema attack rate. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of participants achieving normalized number of attacks < 1.0 per 4 weeks during each of the efficacy evaluation periods was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. |
Day 0 through Day 182, Day 70 through Day 182 |
|
Secondary |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) |
TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. SAE=untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product 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. |
From the first study drug administration up to follow-up (Day 196) |
|
Secondary |
Plasma Concentrations of Lanadelumab |
|
Pre-dose and post-dose at Days 0, 4, 14, 28, 56, 84, 112, 140, 168 and 182 |
|
Secondary |
Plasma Kallikrein (pKal) Activity |
Plasma Kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK ) level to assess pharmacodynamics of lanadelumab. |
Pre-dose and post-dose at Days 4, 14, 28, 56, 84, 112, 140, 168 and 182 |
|
Secondary |
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma |
Number of participants with neutralizing or non-neutralizing antidrug antibodies in plasma was assessed. |
Pre-dose and post-dose at Days 28, 56, 84, 112, 140, 168 and 182 |
|
Secondary |
Number of Participants With Change in Total Angioedema Quality of Life (AE-QoL) Questionnaire Score During the Treatment Period of Day 0 Through Day 182 |
The AE-QoL questionnaire was a self-administered validated instrument to assess health related (HR) QoL among participants with recurrent angioedema. The AE-QoL consisted of 17 disease-specific quality-of-life items, to produce a total AEQoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five point response scale ranging from 0 (Never) to 4 (Very Often). The raw total score (mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0 to 100. Swelling episodes (SE); Trouble Concentrating (TC); Food and Beverages (F&B); negative effects (NE). |
Baseline through Day 182 |
|