Trial Outcomes & Findings for A Study of Lanadelumab (SHP643) in Chinese Participants With Hereditary Angioedema (HAE) (NCT NCT05460325)

NCT ID: NCT05460325

Last Updated: 2024-12-13

Results Overview

TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An SAE is any 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. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: From first dose of study drug up to end of study (up to Day 210)
• Results posted on: 2024-12-13

Participant Flow

Participants took part in the study at 4 investigative sites in China from 22 June 2022 to 28 November 2023.

A total of 20 participants with a diagnosis of hereditary angioedema (HAE) were enrolled in a Run-in Period of 4 to 8 weeks. Participants who experienced ≥1.0 investigator-confirmed HAE attack per 4 weeks during the Run-in Period and who remained eligible per inclusion and exclusion criteria entered the 26-week lanadelumab Treatment Period to receive lanadelumab 300 milligrams (mg).

Participant milestones

Measure	Lanadelumab 300 mg Participants received lanadelumab 300 mg, subcutaneously (SC), once every two weeks (Q2W) for 26 weeks.
Run-in Period (4 or up to 8 Weeks) STARTED	20
Run-in Period (4 or up to 8 Weeks) COMPLETED	20
Run-in Period (4 or up to 8 Weeks) NOT COMPLETED	0
Treatment Period (Weeks 1 to 26) STARTED	20
Treatment Period (Weeks 1 to 26) COMPLETED	20
Treatment Period (Weeks 1 to 26) NOT COMPLETED	0
Safety Follow-up Period (Weeks 27 to 30) STARTED	20
Safety Follow-up Period (Weeks 27 to 30) COMPLETED	20
Safety Follow-up Period (Weeks 27 to 30) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Lanadelumab (SHP643) in Chinese Participants With Hereditary Angioedema (HAE)

Baseline characteristics by cohort

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Age, Continuous	37.8 years STANDARD_DEVIATION 11.60 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment China	20 Participants n=5 Participants
Weight	67.65 kilograms (kg) STANDARD_DEVIATION 13.551 • n=5 Participants
Height	166.83 centimeter (cm) STANDARD_DEVIATION 7.973 • n=5 Participants
Body Mass Index (BMI)	24.18 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 3.927 • n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to end of study (up to Day 210)

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An SAE is any 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. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) TEAEs: Non-Angioedema Attack	15 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) TEAEs: Angioedema Attack	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) SAEs: Non-Angioedema Attack	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) SAEs: Angioedema Attack	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) AESIs: Non-Angioedema Attack	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) AESIs: Angioedema Attack	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to end of study (up to Day 210)

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

Laboratory parameters included clinical chemistry, hematology, coagulation, urinalysis, and serology. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters (including clinical chemistry, hematology, coagulation, urinalysis, and serology) were reported.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to end of study (up to Day 210)

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

Vital signs included measurement of blood pressure, heart rate, body temperature, and respiratory rate. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in vital signs were reported.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities	0 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to end of study (up to Day 210)

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

ECG included heart rate, PR interval, QRS duration, QT interval, corrected QT interval (QTc) interval, QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval, and QT corrected for heart rate by Bazett formula (QTcB) interval. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in ECG were reported.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)	0 Participants

PRIMARY outcome

Timeframe: Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

Physical examination findings by body system were classified as height and weight, general appearance, ears, nose and throat, head and neck, ophthalmological, respiratory, cardiovascular, abdomen, neurological, extremities, dermatological, and lymphatic. Number of participants with clinically significant changes in physical examination findings per investigator interpretation were reported. Only categories with at least one participant with event are reported.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182 Dermatologic System	2 Participants
Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182 Extremities	1 Participants

SECONDARY outcome

Timeframe: Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182

Population: The Pharmacokinetic (PK) Set included all participants in the FAS who had at least 1 evaluable post-dose PK concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Plasma Concentrations of Lanadelumab Day 0	7.64 nanograms per milliliter (ng/mL) Standard Deviation 24.096
Plasma Concentrations of Lanadelumab Day 14: Pre-dose	12336.47 nanograms per milliliter (ng/mL) Standard Deviation 4531.386
Plasma Concentrations of Lanadelumab Day 56: Pre-dose	24857.89 nanograms per milliliter (ng/mL) Standard Deviation 6950.725
Plasma Concentrations of Lanadelumab Day 98: Pre-dose	24170.00 nanograms per milliliter (ng/mL) Standard Deviation 7260.426
Plasma Concentrations of Lanadelumab Day 140: Pre-dose	23821.05 nanograms per milliliter (ng/mL) Standard Deviation 8808.870
Plasma Concentrations of Lanadelumab Day 182: Pre-dose	24610.00 nanograms per milliliter (ng/mL) Standard Deviation 6599.673
Plasma Concentrations of Lanadelumab Day 210	12048.00 nanograms per milliliter (ng/mL) Standard Deviation 3268.807

SECONDARY outcome

Timeframe: Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182

Population: The Pharmacodynamic (PD) Set included all participants in the FAS who had at least 1 evaluable post-dose PD concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.

pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK).

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Plasma Kallikrein (pKal) Activity Day 0	10256.419 ng/mL Standard Deviation 3311.3810
Plasma Kallikrein (pKal) Activity Day 14: Pre-dose	4904.964 ng/mL Standard Deviation 1350.4121
Plasma Kallikrein (pKal) Activity Day 56: Pre-dose	3604.136 ng/mL Standard Deviation 1279.8551
Plasma Kallikrein (pKal) Activity Day 98: Pre-dose	3312.706 ng/mL Standard Deviation 1526.8282
Plasma Kallikrein (pKal) Activity Day 140: Pre-dose	2871.364 ng/mL Standard Deviation 1324.5022
Plasma Kallikrein (pKal) Activity Day 182: Pre-dose	3383.672 ng/mL Standard Deviation 1337.0341
Plasma Kallikrein (pKal) Activity Day 210	3800.187 ng/mL Standard Deviation 1499.9735

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182	0.04 attacks/month Standard Deviation 0.139

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

An HAE attack was confirmed by following symptoms/signs consistent with an attack in atleast one of the following locations:1)Peripheral angioedema:cutaneous swelling involving an extremity,the face,neck,torso,and/or genitourinary region;2)Abdominal angioedema:abdominal pain,with/without abdominal distention,nausea,vomiting,or diarrhea;3)Laryngeal angioedema:stridor,dyspnea, difficulty speaking,difficulty swallowing,throat tightening,or swelling of the tongue,palate,uvula,or larynx.Acute HAE attacks were managed per the investigator's usual care, including use of individualized acute therapy/rescue medications.Acute therapy/rescue medications included Firazyr, fresh frozen plasma (FFP), or other local standard of care.Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks requiring acute treatment occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182	0.01 attacks/month Standard Deviation 0.034

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

The severity of the investigator-confirmed HAE attacks was defined per the HAE attack assessment and reporting procedures (HAARP) definitions: severe (marked limitation in activity, assistance required), moderate (mild to moderate limitation in activity, some assistance needed). Treatment period attack rate per month is calculated as the number of moderate or severe investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182	0.01 attacks/month Standard Deviation 0.034

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

Number of participants with maximum HAE attack severity during the efficacy evaluation period was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 No Attack	18 Participants
Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 Mild	1 Participants
Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 Moderate	1 Participants
Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 Severe	0 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

Time to the first investigator-confirmed HAE attack (days) was calculated from the date and time of the first dose of study drug for that efficacy evaluation period to the date and time of the first investigator-confirmed HAE attack after the first dose for the efficacy evaluation period. The time to the first HAE attack was summarized using Kaplan-Meier (KM) estimates.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182	NA days Median and full range were not evaluable due to low number of participants with events.

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) 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 if the participant had no investigator-confirmed HAE attacks during the efficacy evaluation period. Number of participants who achieved attack-free status for the efficacy evaluation periods were assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182	18 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

A run-in period of 4 weeks was included to determine the participant's baseline attack rate. This period may be extended up to 8 weeks. The normalized number of investigator-confirmed HAE attacks during efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate relative to the run-in period NNA. Number of participants who achieved at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed NNA per 4 weeks relative to the run-in period normalized NNA for the efficacy evaluation periods was assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA ≥50% Reduction	20 Participants
Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA ≥70% Reduction	20 Participants
Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA ≥90% Reduction	19 Participants
Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA 100% Reduction	18 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).

The normalized number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a monthly (28 days) HAE 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 who achieved NNA <1.0 per 4 weeks for the efficacy evaluation period were assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182	20 Participants

SECONDARY outcome

Timeframe: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP). Number analyzed is the number of participants with data available for analyses at the specified timepoint.

Number of participants with neutralizing or non-neutralizing ADA in plasma were assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 0	1 Participants
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 56: Pre-dose	0 Participants
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 98: Pre-dose	0 Participants
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 140: Pre-dose	1 Participants
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 182: Pre-dose	1 Participants
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma Day 210	3 Participants

SECONDARY outcome

Timeframe: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182

Population: The PK set included all participants in the FAS who had at least 1 evaluable post-dose PK concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.

The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the lanadelumab plasma concentrations was assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 0: Positive ADA Result	0.00 ng/mL Standard Deviation NA Standard deviation (SD) was not estimable for a single participant.
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 0: Negative ADA Result	8.04 ng/mL Standard Deviation 24.687
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 56: Pre-dose: Negative ADA Result	24857.89 ng/mL Standard Deviation 6950.725
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 98: Pre-dose: Negative ADA Result	24170.00 ng/mL Standard Deviation 7260.426
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 140: Pre-dose: Positive ADA Result	16700.00 ng/mL Standard Deviation NA SD was not estimable for a single participant.
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 140: Pre-dose: Negative ADA Result	24216.67 ng/mL Standard Deviation 8888.873
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 182: Pre-dose: Positive ADA Result	27800.00 ng/mL Standard Deviation NA SD was not estimable for a single participant.
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 182: Pre-dose: Negative ADA Result	24442.11 ng/mL Standard Deviation 6736.494
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 210: Positive ADA Result	13800.00 ng/mL Standard Deviation 624.500
Plasma Concentrations of Lanadelumab by Immunogenicity Result Day 210: Negative ADA Result	11738.82 ng/mL Standard Deviation 3458.715

SECONDARY outcome

Timeframe: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182

Population: The PD set included all participants in the FAS who had at least 1 evaluable post-dose PD concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.

The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the cHMWK levels was assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 210: Negative ADA Result	3599.373 ng/mL Standard Deviation 1467.1561
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 0: Positive ADA Result	13346.780 ng/mL Standard Deviation NA SD was not estimable for a single participant.
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 0: Negative ADA Result	10093.768 ng/mL Standard Deviation 3319.0248
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 56: Pre-dose: Negative ADA Result	3604.136 ng/mL Standard Deviation 1279.8551
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 98: Pre-dose: Negative ADA Result	3312.706 ng/mL Standard Deviation 1526.8282
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 140: Pre-dose: Positive ADA Result	3733.890 ng/mL Standard Deviation NA SD was not estimable for a single participant.
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 140: Pre-dose: Negative ADA Result	2823.446 ng/mL Standard Deviation 1345.8483
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 182: Pre-dose: Positive ADA Result	4577.960 ng/mL Standard Deviation NA SD was not estimable for a single participant.
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 182: Pre-dose: Negative ADA Result	3320.814 ng/mL Standard Deviation 1342.9683
Plasma Kallikrein Activity cHMWK by Immunogenicity Result Day 210: Positive ADA Result	4938.130 ng/mL Standard Deviation 1367.0128

SECONDARY outcome

Timeframe: Day 0 through Day 182

Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP). Number analyzed is the number of participants with data available for analyses at the specified timepoint.

The number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a normalized monthly (4 weeks, i.e., 28 days). Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the investigator-confirmed HAE attacks during the efficacy evaluation period was assessed.

Outcome measures

Measure	Lanadelumab 300 mg n=20 Participants Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182 At Least One Positive ADA Result	0.00 attacks/month Standard Deviation NA SD was not estimable for a single participant.
Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182 No Positive ADA Result	0.04 attacks/month Standard Deviation 0.142

Adverse Events

Lanadelumab 300 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lanadelumab 300 mg n=20 participants at risk Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	5.0% 1/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Musculoskeletal and connective tissue disorders Spinal stenosis	5.0% 1/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.

Other adverse events

Measure	Lanadelumab 300 mg n=20 participants at risk Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks.
Gastrointestinal disorders Abdominal pain upper	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Investigations Blood uric acid increased	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Infections and infestations COVID-19	50.0% 10/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Nervous system disorders Dizziness	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Hepatobiliary disorders Hepatic function abnormal	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Vascular disorders Hypertension	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
General disorders Injection site pain	20.0% 4/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
General disorders Injection site swelling	15.0% 3/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Infections and infestations Nasopharyngitis	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Gastrointestinal disorders Nausea	15.0% 3/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
Gastrointestinal disorders Toothache	10.0% 2/20 • From start of the study upto follow up (up to Day 210) The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: TrialDisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER