Trial Outcomes & Findings for A Study of Lanadelumab to Prevent Hereditary Angioedema (HAE) Attacks in Children (NCT NCT04070326)

NCT ID: NCT04070326

Last Updated: 2022-05-26

Results Overview

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, is an important medical event. Adverse events of special interest for this study are hypersensitivity reactions and disordered coagulation (hypercoagulability events and bleeding events).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 21 participants
• Primary outcome timeframe: Up to approximately 115 weeks
• Results posted on: 2022-05-26

Participant Flow

Total 24 participants were screened and 21 participants were enrolled in the study at 15 investigative sites in the United States, Canada, Spain, Hungary, and Germany from 19 August 2019 to 30 October 2021.

Enrolled participants were observed in 12-week Baseline Observation Period. Participants who experienced ≥1.0 angioedema attacks per 3 months during 12-week Baseline Observation Period and who remained eligible per inclusion criteria entered lanadelumab treatment period(TP). Pediatric participants aged 2 to <12 years received lanadelumab subcutaneous (SC) injection at a dose of 150 milligrams (mg) for every 4 weeks (q4wks) or for every 2 weeks (q2wks) based on age over 52-week Treatment Period.

Participant milestones

Measure	Lanadelumab 150 mg: Age 2 to <6 Years Participants aged 2 to \<6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg: Age 6 to <12 Years Participants aged 6 to \<12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator's discretion and sponsor's medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.
Baseline Observation-12 Weeks Before TP STARTED	4	17
Baseline Observation-12 Weeks Before TP COMPLETED	4	17
Baseline Observation-12 Weeks Before TP NOT COMPLETED	0	0
Treatment Period A (Weeks 1 to 26) STARTED	4	17
Treatment Period A (Weeks 1 to 26) COMPLETED	3	17
Treatment Period A (Weeks 1 to 26) NOT COMPLETED	1	0
Treatment Period B (Weeks 27 to 52) STARTED	3	17
Treatment Period B (Weeks 27 to 52) COMPLETED	3	17
Treatment Period B (Weeks 27 to 52) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Lanadelumab 150 mg: Age 2 to <6 Years Participants aged 2 to \<6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg: Age 6 to <12 Years Participants aged 6 to \<12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator's discretion and sponsor's medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.
Treatment Period A (Weeks 1 to 26) Withdrawal by Parent/Guardian	1	0

Baseline Characteristics

A Study of Lanadelumab to Prevent Hereditary Angioedema (HAE) Attacks in Children

Baseline characteristics by cohort

Measure	Lanadelumab 150 mg: Age 2 to <6 Years n=4 Participants Participants aged 2 to \<6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg: Age 6 to <12 Years n=17 Participants Participants aged 6 to \<12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator's discretion and sponsor's medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.	Total n=21 Participants Total of all reporting groups
Age, Continuous	4.45 years STANDARD_DEVIATION 0.843 • n=5 Participants	8.68 years STANDARD_DEVIATION 1.391 • n=7 Participants	7.88 years STANDARD_DEVIATION 2.134 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 115 weeks

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, is an important medical event. Adverse events of special interest for this study are hypersensitivity reactions and disordered coagulation (hypercoagulability events and bleeding events).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) SAEs	0 Participants	0 Participants
Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) AESIs	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to approximately 115 weeks

Population: The Safety Analysis Set consisted of all participants who received study drug.

Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With Clinically Significant Laboratory Assessment Abnormalities	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to approximately 115 weeks

Population: The Safety Analysis Set consisted of all participants who received study drug.

Vital signs included blood pressure, heart rate, body temperature, and respiratory rate.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With Clinically Significant Vital Signs Measurements	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The Pharmacokinetic (PK) Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value. Number analyzed is the number of participants with data available for analysis at the given timepoint.

The plasma concentration of lanadelumab over treatment period was assessed.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 1 Day 0	0.000 nanograms per milliliter (ng/mL) Standard Deviation 0.0000	11.735 nanograms per milliliter (ng/mL) Standard Deviation 39.2984
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 2 Day 4	32407.215 nanograms per milliliter (ng/mL) Standard Deviation 9785.4332	20349.609 nanograms per milliliter (ng/mL) Standard Deviation 12587.7085
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 3 Day 14	20443.818 nanograms per milliliter (ng/mL) Standard Deviation 7800.4019	14589.883 nanograms per milliliter (ng/mL) Standard Deviation 4734.4461
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 4 Day 28	10636.682 nanograms per milliliter (ng/mL) Standard Deviation 6168.5347	21198.858 nanograms per milliliter (ng/mL) Standard Deviation 8378.3961
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 8 Day 56	10433.382 nanograms per milliliter (ng/mL) Standard Deviation 3345.1718	27751.659 nanograms per milliliter (ng/mL) Standard Deviation 10048.7527
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 12 Day 84	14758.407 nanograms per milliliter (ng/mL) Standard Deviation 8392.8620	24895.121 nanograms per milliliter (ng/mL) Standard Deviation 11852.7671
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 16 Day 112	15020.780 nanograms per milliliter (ng/mL) Standard Deviation 5730.4397	31053.260 nanograms per milliliter (ng/mL) Standard Deviation 14012.6464
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 20 Day 140	13318.715 nanograms per milliliter (ng/mL) Standard Deviation 4432.0728	26534.885 nanograms per milliliter (ng/mL) Standard Deviation 11234.6051
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 24 Day 168	12189.214 nanograms per milliliter (ng/mL) Standard Deviation 11367.4241	26166.340 nanograms per milliliter (ng/mL) Standard Deviation 11070.0337
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 26 Day 182	25630.909 nanograms per milliliter (ng/mL) Standard Deviation 11054.3701	25372.349 nanograms per milliliter (ng/mL) Standard Deviation 8242.4858
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 28 Day 196	14293.013 nanograms per milliliter (ng/mL) Standard Deviation 6014.0384	25238.600 nanograms per milliliter (ng/mL) Standard Deviation 9921.4264
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 36 Day 252	23110.526 nanograms per milliliter (ng/mL) Standard Deviation 18241.5743	19058.886 nanograms per milliliter (ng/mL) Standard Deviation 12079.1976
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 44 Day 308	22687.442 nanograms per milliliter (ng/mL) Standard Deviation 20911.9442	15774.463 nanograms per milliliter (ng/mL) Standard Deviation 12043.0984
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 52 Day 364	27178.967 nanograms per milliliter (ng/mL) Standard Deviation 24111.9243	17239.653 nanograms per milliliter (ng/mL) Standard Deviation 11975.4861
Plasma Concentrations of Lanadelumab Over The Treatment Period Visit 56 Day 392 (End of Study Visit)	32400.148 nanograms per milliliter (ng/mL) Standard Deviation 24303.4128	15689.458 nanograms per milliliter (ng/mL) Standard Deviation 11811.7412

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma	37.7 micrograms per mL (μg/mL) Geometric Coefficient of Variation 30.1	39.0 micrograms per mL (μg/mL) Geometric Coefficient of Variation 39.2

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma	24.6 μg/mL Geometric Coefficient of Variation 34.0	33.2 μg/mL Geometric Coefficient of Variation 37.7

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma	11.1 µg/mL Geometric Coefficient of Variation 46.5	24.8 µg/mL Geometric Coefficient of Variation 37.3

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma	122 hours (h) Interval 108.0 to 135.0	86.0 hours (h) Interval 66.0 to 137.0

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma	690 μg.day/mL Geometric Coefficient of Variation 34.0	464 μg.day/mL Geometric Coefficient of Variation 37.7

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Terminal Half-life (t1/2) of Lanadelumab in Plasma	11.7 days Interval 10.2 to 13.9	12.6 days Interval 9.59 to 27.3

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Apparent Clearance (CL/F) of Lanadelumab	0.00906 L/h Geometric Coefficient of Variation 34.0	0.0135 L/h Geometric Coefficient of Variation 37.8

PRIMARY outcome

Timeframe: Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Apparent Volume of Distribution (V/F) of Lanadelumab	3.63 L Geometric Coefficient of Variation 25.9	5.59 L Geometric Coefficient of Variation 39.2

SECONDARY outcome

Timeframe: Day 0 (after start of study drug administration) through Day 364 (Week 52)

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

Normalized number of investigator-confirmed HAE attacks during overall period are expressed as a monthly HAE attack rate. Investigator-confirmed HAE attack rate was calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is defined as the symptoms or signs consistent with an attack in >=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).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period	0.07 HAE attacks per month Standard Deviation 0.219	0.08 HAE attacks per month Standard Deviation 0.157

SECONDARY outcome

Timeframe: Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

Normalized number of investigator-confirmed HAE attacks during each efficacy evaluation period other than overall treatment period are expressed as a monthly HAE attack rate. Investigator-confirmed HAE attack rate was calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28 days. A HAE attack is defined as symptoms or signs consistent with an attack in at least 1 of 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 the tongue, palate, uvula, or larynx).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period Treatment Period B	0.28 HAE attacks per month Standard Deviation 0.878	0.08 HAE attacks per month Standard Deviation 0.142
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period Overall Presumed Steady-state Period	0.09 HAE attacks per month Standard Deviation 0.288	0.07 HAE attacks per month Standard Deviation 0.143
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period Treatment Period A	0.15 HAE attacks per month Standard Deviation 0.308	0.08 HAE attacks per month Standard Deviation 0.207
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period Presumed Steady-state Period for Treatment Period A	0.25 HAE attacks per month Standard Deviation 0.433	0.06 HAE attacks per month Standard Deviation 0.192

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

Time to first investigator-confirmed HAE attack (days) for each efficacy evaluation period was calculated from date and time of first dose of lanadelumab for that efficacy evaluation period to date and time of first investigator-confirmed HAE attack after first open-label dose for that efficacy evaluation period. A HAE attack is defined as symptoms or signs consistent with an attack in >=1 of 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). Kaplan-Meier Method was used for analysis.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period Treatment Period A	NA days The median and 95% confidence interval (CI) were not evaluable due to low number of events.	NA days The median and 95% CI were not evaluable due to low number of events.
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period Presumed Steady-state Period for Treatment Period A	NA days The median and 95% CI were not evaluable due to low number of events.	NA days The median and 95% CI were not evaluable due to low number of events.
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period Treatment Period B	NA days The median and 95% CI were not evaluable due to low number of events.	NA days The median and 95% CI were not evaluable due to low number of events.
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period Overall Treatment Period	NA days The median and 95% CI were not avaluable due to low number of events.	NA days The median and 95% CI were not avaluable due to low number of events.
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period Overall Presumed Steady-state Period	NA days The median and 95% CI were not evaluable due to low number of events.	NA days The median and 95% CI were not evaluable due to low number of events.

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

The normalized number of investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is 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).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period Overall Treatment Period	0.07 HAE attacks per month Standard Deviation 0.219	0.07 HAE attacks per month Standard Deviation 0.140
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period Overall Presumed Steady-state Period	0.09 HAE attacks per month Standard Deviation 0.288	0.06 HAE attacks per month Standard Deviation 0.126
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period Treatment Period A	0.15 HAE attacks per month Standard Deviation 0.308	0.07 HAE attacks per month Standard Deviation 0.175
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A	0.25 HAE attacks per month Standard Deviation 0.433	0.04 HAE attacks per month Standard Deviation 0.135
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period Treatment Period B	0.28 HAE attacks per month Standard Deviation 0.878	0.06 HAE attacks per month Standard Deviation 0.132

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

The normalized number of moderate or severe investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is 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).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period	0.07 HAE attacks per month Standard Deviation 0.219	0.07 HAE attacks per month Standard Deviation 0.144
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period	0.09 HAE attacks per month Standard Deviation 0.288	0.06 HAE attacks per month Standard Deviation 0.125
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A	0.15 HAE attacks per month Standard Deviation 0.308	0.07 HAE attacks per month Standard Deviation 0.175
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Steady-state Period for Treatment Period A	0.25 HAE attacks per month Standard Deviation 0.433	0.04 HAE attacks per month Standard Deviation 0.135
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B	0.3 HAE attacks per month Standard Deviation 0.88	0.1 HAE attacks per month Standard Deviation 0.13

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

The normalized number of high morbidity investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is 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).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B	0.00 HAE attacks per month Standard Deviation 0.000	0.01 HAE attacks per month Standard Deviation 0.039
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period	0.01 HAE attacks per month Standard Deviation 0.044	0.01 HAE attacks per month Standard Deviation 0.039
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period	0.02 HAE attacks per month Standard Deviation 0.072	0.01 HAE attacks per month Standard Deviation 0.039
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A	0.04 HAE attacks per month Standard Deviation 0.077	0.00 HAE attacks per month Standard Deviation 0.000
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A	0.08 HAE attacks per month Standard Deviation 0.144	0.00 HAE attacks per month Standard Deviation 0.000

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

Characteristics of investigator-confirmed HAE attacks for each efficacy evaluation period included duration, severity, attack location, and rescue medication use. A HAE attack is 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). Only categories with data are reported.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Mean HAE attack duration: 0 hour	3 Participants	14 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Mean HAE attack duration: <12 hours	1 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Mean HAE attack duration: >24-48 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Maximum HAE attack severity: No attack	3 Participants	14 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Maximum HAE attack severity: Moderate	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Maximum HAE attack severity: Severe	1 Participants	0 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Mean HAE attack duration: 0 hour	2 Participants	15 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Mean HAE attack duration: <12 hours	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Mean HAE attack duration: >24-48 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Maximum HAE attack severity: No attack	2 Participants	15 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Maximum HAE attack severity: Moderate	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Maximum HAE attack severity: Severe	1 Participants	0 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Mean HAE attack duration: 0 hour	9 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Maximum HAE attack severity: Moderate	0 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Mean HAE attack duration: >0-<12 hours	1 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Mean HAE attack duration: 12-24 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Mean HAE attack duration: >48 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Maximum HAE attack severity: No attack	9 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Maximum HAE attack severity: Moderate	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Maximum HAE attack severity: Severe	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Mean HAE attack duration: 0 hour	10 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Mean HAE attack duration: >0-<12 hours	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Mean HAE attack duration: >24-48 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Maximum HAE attack severity: No attack	10 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Maximum HAE attack severity: Severe	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Mean HAE attack duration: 0 hour	9 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Mean HAE attack duration: >0-<12 hours	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Mean HAE attack duration: >48 hours	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Maximum HAE attack severity: No attack	9 Participants	13 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Maximum HAE attack severity: Moderate	0 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Maximum HAE attack severity: Severe	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: HAE Primary Attack Location: Peripheral	1 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: HAE Primary Attack Location: Abdominal	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: HAE Attack Derived Location: Peripheral	1 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: HAE Attack Derived Location: Abdominal	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Rescue Medication Use: No Use	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Rescue Medication Use: Icatibant	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Rescue Medication Use: C1-INH (Nano-filtered C1-INH)	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period A: Rescue Medication Use: C1-INH (Plasma-derived)	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A:Rescue Medication Use:Plasma-derived C1-INH	1 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: HAE Primary Attack Location: Peripheral	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: HAE Primary Attack Location: Abdominal	1 Participants	0 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: HAE Attack Derived Location: Peripheral	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: HAE Attack Derived Location: Abdominal	1 Participants	0 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Rescue Medication Use: No Use	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Presumed Steady-state Period for Treatment Period A: Rescue Medication Use: Icatibant	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: HAE Primary Attack Location: Peripheral	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: HAE Primary Attack Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: HAE Attack Derived Location: Peripheral	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: HAE Attack Derived Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Rescue Medication Use: No Use	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Rescue Medication Use: Icatibant	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Treatment Period B: Rescue Medication Use: C1-INH (Plasma-derived C1-INH)	1 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: HAE Primary Attack Location: Peripheral	1 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: HAE Primary Attack Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: HAE Attack Derived Location: Peripheral	1 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: HAE Attack Derived Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Rescue Medication Use: No Use	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Rescue Medication Use: Icatibant	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Rescue Medication Use: C1-INH (Nano-filtered C1-INH)	0 Participants	1 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Treatment Period: Rescue Medication Use: C1-INH (Plasma-derived C1-INH)	1 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: HAE Primary Attack Location: Peripheral	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: HAE Primary Attack Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: HAE Attack Derived Location: Peripheral	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: HAE Attack Derived Location: Abdominal	1 Participants	4 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Rescue Medication Use: No Use	0 Participants	3 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Rescue Medication Use: Icatibant	0 Participants	2 Participants
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period Overall Presumed Steady-state Period: Rescue Medication Use: C1-INH (Plasma-derived C1-INH)	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Population: The Safety Analysis Set consisted of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

A HAE attack is 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).

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=11 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With HAE Attack-Free Status for Each Evaluation Period Treatment Period A	3 Participants	14 Participants
Number of Participants With HAE Attack-Free Status for Each Evaluation Period Presumed Steady-state Period for Treatment Period A	2 Participants	15 Participants
Number of Participants With HAE Attack-Free Status for Each Evaluation Period Treatment Period B	9 Participants	13 Participants
Number of Participants With HAE Attack-Free Status for Each Evaluation Period Overall Treatment Period	10 Participants	13 Participants
Number of Participants With HAE Attack-Free Status for Each Evaluation Period Overall Presumed Steady-state Period	9 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Population: The Pharmacodynamic (PD) Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PD value. Number analyzed is the number of participants with data available for analysis at the given timepoint.

pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics of lanadelumab.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Plasma Kallikrein (pKal) Activity Visit 1 Day 0	30.2500 percentage of cHMWK Standard Deviation 13.61017	45.6438 percentage of cHMWK Standard Deviation 25.79470
Plasma Kallikrein (pKal) Activity Visit 2 Day 4	16.4000 percentage of cHMWK Standard Deviation 8.94036	32.2857 percentage of cHMWK Standard Deviation 17.89606
Plasma Kallikrein (pKal) Activity Visit 3 Day 14	9.5750 percentage of cHMWK Standard Deviation 4.05740	25.7176 percentage of cHMWK Standard Deviation 11.75565
Plasma Kallikrein (pKal) Activity Visit 4 Day 28	18.8500 percentage of cHMWK Standard Deviation 14.15968	26.1571 percentage of cHMWK Standard Deviation 11.76616
Plasma Kallikrein (pKal) Activity Visit 8 Day 56	15.1333 percentage of cHMWK Standard Deviation 12.95582	24.6267 percentage of cHMWK Standard Deviation 14.28963
Plasma Kallikrein (pKal) Activity Visit 12 Day 84	18.2333 percentage of cHMWK Standard Deviation 17.91768	24.7214 percentage of cHMWK Standard Deviation 12.84339
Plasma Kallikrein (pKal) Activity Visit 16 Day 112	10.7333 percentage of cHMWK Standard Deviation 5.48118	18.0000 percentage of cHMWK Standard Deviation 11.05992
Plasma Kallikrein (pKal) Activity Visit 20 Day 140	15.2000 percentage of cHMWK Standard Deviation 16.96202	16.3417 percentage of cHMWK Standard Deviation 12.53841
Plasma Kallikrein (pKal) Activity Visit 24 Day 168	21.9000 percentage of cHMWK Standard Deviation 20.71545	19.6167 percentage of cHMWK Standard Deviation 16.61762
Plasma Kallikrein (pKal) Activity Visit 26 Day 182	17.9000 percentage of cHMWK Standard Deviation 14.29021	18.6818 percentage of cHMWK Standard Deviation 10.54332
Plasma Kallikrein (pKal) Activity Visit 28 Day 196	9.2000 percentage of cHMWK Standard Deviation 2.52389	14.6571 percentage of cHMWK Standard Deviation 7.29939
Plasma Kallikrein (pKal) Activity Visit 36 Day 252	15.2000 percentage of cHMWK Standard Deviation 13.16397	16.3067 percentage of cHMWK Standard Deviation 10.26008
Plasma Kallikrein (pKal) Activity Visit 44 Day 308	13.5333 percentage of cHMWK Standard Deviation 7.24316	23.2750 percentage of cHMWK Standard Deviation 15.23577
Plasma Kallikrein (pKal) Activity Visit 52 Day 364	10.7333 percentage of cHMWK Standard Deviation 2.87112	14.4733 percentage of cHMWK Standard Deviation 8.51448
Plasma Kallikrein (pKal) Activity Visit 56 Day 392 EOS	10.9000 percentage of cHMWK Standard Deviation 3.15753	19.4286 percentage of cHMWK Standard Deviation 14.57677

SECONDARY outcome

Timeframe: Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392

Population: The Safety Analysis Set consisted of all participants who received study drug. Number analyzed are the number of participants with data available for given category.

Immunogenicity was measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma.

Outcome measures

Measure	Lanadelumab 150 mg, q4wks n=4 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=17 Participants Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Number of Participants With Immunogenicity Status as Positive or Negative Visit 4 Day 28: ADA Positive	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Visit 4 Day 28: ADA Positive (Neutralizing)	0 Participants	0 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Visit 4 Day 28: ADA Positive (Non-neutralizing)	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Baseline (Day 0): ADA Negative	4 Participants	17 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Baseline (Day 0): ADA Positive	0 Participants	0 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Baseline (Day 0): ADA Positive (Neutralizing)	0 Participants	0 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Baseline (Day 0): ADA Positive (Non-neutralizing)	0 Participants	0 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Visit 4 Day 28: ADA Negative	4 Participants	13 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period A: ADA Negative	4 Participants	13 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period A: ADA Positive	0 Participants	3 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period A: ADA Positive (Neutralizing)	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period A: ADA Positive (Non-neutralizing)	0 Participants	3 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period B: ADA Negative	3 Participants	15 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period B: ADA Positive	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period B: ADA Positive (Neutralizing)	0 Participants	0 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Treatment Period B: ADA Positive (Non-neutralizing)	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Study Period: ADA Negative	4 Participants	13 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Study Period: ADA Positive	0 Participants	3 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Study Period: ADA Positive (Neutralizing)	0 Participants	1 Participants
Number of Participants With Immunogenicity Status as Positive or Negative Overall Study Period: ADA Positive (Non-neutralizing)	0 Participants	3 Participants

Adverse Events

Lanadelumab 150 mg, q4wks

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Lanadelumab 150 mg, q2wks

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lanadelumab 150 mg, q4wks n=11 participants at risk Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).	Lanadelumab 150 mg, q2wks n=18 participants at risk Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
Eye disorders Diplopia	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Eye disorders Eye inflammation	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Gastrointestinal disorders Abdominal pain	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 3 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Gastrointestinal disorders Tooth loss	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Gastrointestinal disorders Toothache	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Injection site pain	18.2% 2/11 • Number of events 12 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	33.3% 6/18 • Number of events 76 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Injection site erythema	18.2% 2/11 • Number of events 8 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 21 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Injection site swelling	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 3 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Pyrexia	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Administration site pain	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Fatigue	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Feeling cold	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Injection site injury	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
General disorders Injection site reaction	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Immune system disorders Seasonal allergy	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Nasopharyngitis	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Rhinitis	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Upper respiratory tract infection	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Adenoiditis	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Asymptomatic COVID-19	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations COVID-19	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Gastroenteritis viral	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Influenza	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Otitis media	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Paronychia	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Pharyngitis streptococcal	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Sinusitis	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Skin abrasion	9.1% 1/11 • Number of events 3 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	16.7% 3/18 • Number of events 13 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Joint injury	18.2% 2/11 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Contusion	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Fall	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Limb injury	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Injury, poisoning and procedural complications Skin laceration	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Investigations Eosinophil count increased	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Musculoskeletal and connective tissue disorders Growing pains	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	16.7% 3/18 • Number of events 4 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Nervous system disorders Headache	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	11.1% 2/18 • Number of events 3 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Psychiatric disorders Affect lability	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Nasal congestion	18.2% 2/11 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	9.1% 1/11 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Skin and subcutaneous tissue disorders Erythema	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Vascular disorders Haematoma	0.00% 0/11 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	5.6% 1/18 • Number of events 2 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
Skin and subcutaneous tissue disorders Skin abrasion	9.1% 1/11 • Number of events 1 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.	0.00% 0/18 • Up to approximately 115 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Overall number at risk are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.

Additional Information

Study Director

Takeda

Phone: +1 866 842 5335

Email: ClinicalTransparency@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER