Trial Outcomes & Findings for A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (NCT NCT04444895)

Last Updated: 2024-06-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

73 participants

Primary outcome timeframe

From Day 0 up to Day 182

Results posted on

2024-06-17

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.

Participants with a diagnosis of non-histaminergic angioedema rolled over from the study SHP643-303 (NCT04206605) to receive lanadelumab 300 mg every 2 weeks (Q2W) of whom 2 participants switched to lanadelumab 300 mg at a reduced frequency of every 4 weeks (Q4W) for some time during the study.

Participant milestones

Participant milestones
Measure	Lanadelumab 300 mg Q2W 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.
Overall Study STARTED	73
Overall Study Reduced-dose Safety AnalysisSet(RD-SFAS)	2
Overall Study COMPLETED	64
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Lanadelumab 300 mg Q2W 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.
Overall Study Adverse Event	2
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	5

Baseline Characteristics

Number of participants analyzed is the number of participants with data available for weight at the Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.
Age, Continuous	43.7 years STANDARD_DEVIATION 12.63 • n=73 Participants
Sex: Female, Male Female	59 Participants n=73 Participants
Sex: Female, Male Male	14 Participants n=73 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=73 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=73 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=73 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=73 Participants
Race (NIH/OMB) Asian	4 Participants n=73 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=73 Participants
Race (NIH/OMB) Black or African American	4 Participants n=73 Participants
Race (NIH/OMB) White	64 Participants n=73 Participants
Race (NIH/OMB) More than one race	0 Participants n=73 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=73 Participants
Region of Enrollment Canada	5 Participants n=73 Participants
Region of Enrollment France	1 Participants n=73 Participants
Region of Enrollment Germany	3 Participants n=73 Participants
Region of Enrollment Hungary	2 Participants n=73 Participants
Region of Enrollment Italy	7 Participants n=73 Participants
Region of Enrollment Japan	4 Participants n=73 Participants
Region of Enrollment Netherlands	3 Participants n=73 Participants
Region of Enrollment Poland	6 Participants n=73 Participants
Region of Enrollment Spain	3 Participants n=73 Participants
Region of Enrollment United States	39 Participants n=73 Participants
Weight	81.52 kilograms (kg) STANDARD_DEVIATION 23.129 • n=72 Participants • Number of participants analyzed is the number of participants with data available for weight at the Baseline.
Height	166.75 centimeters (cm) STANDARD_DEVIATION 8.938 • n=73 Participants
Body Mass Index (BMI)	29.23 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 7.972 • n=72 Participants • Number of participants analyzed is the number of participants with data available for BMI at the Baseline.

PRIMARY outcome

Timeframe: From Day 0 up to Day 182

Population: The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period Any TEAEs: Non-Angioedema Attack	55 Participants	1 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 Any TEAEs: Angioedema Attack	61 Participants	1 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 AESI: Non-Angioedema Attack	1 Participants	0 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 AESI: Angioedema Attack	0 Participants	0 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 Any SAEs: Non-Angioedema Attack	5 Participants	1 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 Any SAEs: Angioedema Attack	3 Participants	0 Participants

PRIMARY outcome

Timeframe: From Day 183 up to Day 196

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up Any TEAEs: Non-Angioedema Attack	4 Participants	0 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 Any TEAEs: Angioedema Attack	19 Participants	0 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 AESI: Non-Angioedema Attack	0 Participants	0 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 AESI: Angioedema Attack	0 Participants	0 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 Any SAEs: Non-Angioedema Attack	0 Participants	0 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 Any SAEs: Angioedema Attack	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 up to 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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182	595 angioedema attacks	2 angioedema attacks

SECONDARY outcome

Timeframe: From Day 0 up to 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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182	391 angioedema attacks	2 angioedema attacks

SECONDARY outcome

Timeframe: From Day 0 up to 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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182	232 angioedema attacks	1 angioedema attacks

SECONDARY outcome

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

Population: The Pharmacokinetic (PK) Set included all participants in the SFAS who had at least 1 evaluable postdose PK concentration value. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

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

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=68 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Day 0	14419.068 nanograms per milliliter (ng/mL) Standard Deviation 13208.1952	NA nanograms per milliliter (ng/mL) Standard Deviation NA The data were not estimable as the values were below the lower limit of quantification.
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Day 84	17021.002 nanograms per milliliter (ng/mL) Standard Deviation 10116.5279	7047.860 nanograms per milliliter (ng/mL) Standard Deviation NA The standard deviation was not estimable for a single participant.
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Day 140	21138.057 nanograms per milliliter (ng/mL) Standard Deviation 12076.9186	4944.010 nanograms per milliliter (ng/mL) Standard Deviation NA The standard deviation was not estimable for a single participant.
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Day 182	18799.596 nanograms per milliliter (ng/mL) Standard Deviation 12054.1105	14573.340 nanograms per milliliter (ng/mL) Standard Deviation NA The standard deviation was not estimable for a single participant.

SECONDARY outcome

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

Population: The Pharmacodynamic (PD) Set included all participants in the SFAS who had at least 1 evaluable postdose PD concentration value. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=67 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Plasma Kallikrein (pKal) Activity Day 0	15.306 percentage of cHMWK Standard Deviation 15.2413	NA percentage of cHMWK Standard Deviation NA The data were not estimable as the values were below the lower limit of quantification.
Plasma Kallikrein (pKal) Activity Day 84	17.586 percentage of cHMWK Standard Deviation 9.2437	21.600 percentage of cHMWK Standard Deviation NA The standard deviation was not estimable for a single participant.
Plasma Kallikrein (pKal) Activity Day 140	17.238 percentage of cHMWK Standard Deviation 9.1590	44.700 percentage of cHMWK Standard Deviation NA The standard deviation was not estimable for a single participant.
Plasma Kallikrein (pKal) Activity Day 182	15.515 percentage of cHMWK Standard Deviation 9.2074	37.100 percentage of cHMWK Standard Deviation NA The standard deviation was not estimable for a single participant.

SECONDARY outcome

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

Population: The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=72 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma Day 0	2 Participants	—
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma Day 84	2 Participants	—
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma Day 140	3 Participants	—
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma Day 182	4 Participants	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=66 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period	-12.73 score on a scale Standard Deviation 20.696	—

SECONDARY outcome

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

Population: The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). Number analyzed is the number of participants with data available for analysis at the specified time point. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

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.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=73 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Participants With Any Pause During Injection Day 28	5 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 42	3 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 56	3 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 70	4 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 84	4 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 98	1 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 112	2 Participants	1 Participants
Number of Participants With Any Pause During Injection Day 126	2 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 140	3 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 168	1 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 0	3 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 14	5 Participants	0 Participants
Number of Participants With Any Pause During Injection Day 154	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 up to Day 196

Population: The RD-SFAS Set was a subset of the SFAS Set and included participants who switched from lanadelumab 300 mg Q2W to a lanadelumab 300 mg Q4W dosing regimen as recorded on the Dose Frequency Modification electronic case report form. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=2 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
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 Any TEAEs: Non-Angioedema Attack	2 Participants	1 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 Any TEAEs: Angioedema Attack	0 Participants	1 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 AESI: Non-Angioedema Attack	0 Participants	0 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 AESI: Angioedema Attack	0 Participants	0 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 Any SAEs: Non-Angioedema Attack	0 Participants	1 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 Any SAEs: Angioedema Attack	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 up to Day 182

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=2 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen	0 angioedema attacks	2 angioedema attacks

SECONDARY outcome

Timeframe: From Day 0 up to Day 182

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=2 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen	0 angioedema attacks	2 angioedema attacks

SECONDARY outcome

Timeframe: From Day 0 up to 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 BP \<90 mmHg, requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal.

Outcome measures

Outcome measures
Measure	Lanadelumab 300 mg Q2W n=2 Participants Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Q4W n=2 Participants Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen	0 angioedema attacks	1 angioedema attacks

Adverse Events

Lanadelumab 300 mg Every 2 Weeks

Serious events: 7 serious events

Other events: 65 other events

Deaths: 0 deaths

Lanadelumab 300 mg Every 4 Weeks

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lanadelumab 300 mg Every 2 Weeks n=73 participants at risk Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Every 4 Weeks n=2 participants at risk Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Cardiac disorders Acute myocardial infarction	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Skin and subcutaneous tissue disorders Angioedema	4.1% 3/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Infections and infestations Arthritis viral	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Infections and infestations Cellulitis	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Vascular disorders Deep vein thrombosis	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Infections and infestations Device related sepsis	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Metabolism and nutrition disorders Lactic acidosis	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Psychiatric disorders Suicide attempt	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Other adverse events

Other adverse events
Measure	Lanadelumab 300 mg Every 2 Weeks n=73 participants at risk Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.	Lanadelumab 300 mg Every 4 Weeks n=2 participants at risk Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor at any point during the 26-week treatment period were included in this group.
Skin and subcutaneous tissue disorders Angioedema	83.6% 61/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 7/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Infections and infestations COVID-19	23.3% 17/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Eye disorders Eye swelling	0.00% 0/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
General disorders Fatigue	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Nervous system disorders Headache	13.7% 10/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
General disorders Injection site pain	11.0% 8/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Injury, poisoning and procedural complications Ligament sprain	5.5% 4/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
General disorders Malaise	1.4% 1/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	50.0% 1/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Gastrointestinal disorders Nausea	8.2% 6/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Infections and infestations Upper respiratory tract infection	8.2% 6/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
Skin and subcutaneous tissue disorders Urticaria	5.5% 4/73 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.	0.00% 0/2 • From the first study drug administration up to follow-up (Day 196) The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER