Hereditary Angioedema
Conditions
Keywords
Lanadelumab
Brief summary
The main aims of this study are to learn how lanadelumab moves through a child's body and if the children have any medical problems from lanadelumab. Other aims are to learn if prophylactic treatment with lanadelumab reduces the number and severity of HAE attacks in children, how lanadelumab affects the child's body, and if the children develop antibodies to lanadelumab. The study doctors will treat acute HAE attacks according to their standard practice. Participants will receive lanadelumab for up to 52 weeks. When they start treatment, participants will visit their clinic every week for the first 4 weeks. Then, they will visit their clinic every 4 weeks during treatment.
Detailed description
This study will consists of 52-week treatment period and a 2 or 4-weeks follow-up period (depending on the treatment schedule). 52-week treatment period comprises of a 26-week treatment period A (Day 0 to Day 182) and a 26-week treatment period B (Day 183 to Day 364). Participants who complete treatment period A will immediately continue into treatment period B.
Interventions
DRUGLanadelumab
Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period.
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Be a child (male or female) 2 to lesser than (\<) 12 years of age at the time of screening. * Documented diagnosis of HAE (Type I or II) based upon both of the following: 1. Documented clinical history consistent with HAE (SC or mucosal, nonpruritic swelling episodes without accompanying urticarial). 2. Diagnostic testing results obtained during screening from a sponsor- approved central laboratory that confirm C1-INH functional level \< 40 percent (%) of the normal level. Participants with functional C1 esterase inhibitor (C1-INH) level 40-50% of the normal level may be enrolled if they also have a complement4 (C4) level below the normal range. With prior sponsor approval, participants may be retested during the baseline observation period if results are incongruent with clinical history or believed by the investigator to be confounded by recent complement1 (C1) inhibitor use. * A historical baseline HAE attack rate of at least 1 attack per 3 months. Note: In addition, participants who experience greater than or equal to (\>=)1.0 angioedema attacks per three months during the 12-week baseline observation period and who remain eligible per the inclusion criteria will enter the lanadelumab treatment period. * Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures. * Have a parent(s)/legal guardian who is informed of the nature of the study and can provide written informed consent for the child to participate in the study before any study-specific procedures are performed (with assent from the child when appropriate). * Females of childbearing potential must agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol through the duration of the study from screening through 70 days after the final study visit.
Exclusion criteria
* Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH, idiopathic angioedema, or recurrent angioedema associated with urticaria. * Dosing with an investigational drug or exposure to an investigational device within 4 weeks prior to screening. * Be pregnant or breastfeeding. * Have initiated androgen treatment (eg, stanozolol, danazol, oxandrolone, methyltestosterone, and testosterone) within 2 weeks prior to entering the observation period. * Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening. * Have any active infectious illness or fever defined as an oral temperature greater than (\>) 38 degree celsius (°C) (100.4 fahrenheit \[°F\]), tympanic \> 38.5°C (101.3°F) , axillary \> 38°C (100.4°F), or rectal/core \> 38.5°C (101.3°F) within 24 hours prior to the first dose of study drug in treatment period A. * Have any HAE attack that is not resolved prior to the first dose of study drug in treatment period A. * Have any of the following liver function test abnormalities: alanine aminotransferase (ALT) \> 3\*upper limit of normal (ULN), or aspartate aminotransferase (AST) \> 3\*ULN, or total bilirubin \> 2\*ULN (unless the bilirubin elevation is a result of Gilbert's syndrome). * Have any condition (any surgical or medical condition) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (eg, significant pre-existing illness or other major comorbidity that the investigator considers may confound the interpretation of study results). * Participant has a known hypersensitivity to the investigational product or its components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution (V/F) of Lanadelumab | 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 | — |
| Number of Participants With Clinically Significant Laboratory Assessment Abnormalities | Up to approximately 115 weeks | Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion. |
| Number of Participants With Clinically Significant Vital Signs Measurements | Up to approximately 115 weeks | Vital signs included blood pressure, heart rate, body temperature, and respiratory rate. |
| Plasma Concentrations of Lanadelumab Over The Treatment Period | Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392 | The plasma concentration of lanadelumab over treatment period was assessed. |
| Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma | 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 | — |
| Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma | 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 | — |
| Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma | 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 | — |
| Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma | 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 | — |
| Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma | 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 | — |
| Terminal Half-life (t1/2) of Lanadelumab in Plasma | 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 | — |
| Apparent Clearance (CL/F) of Lanadelumab | 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 | — |
| Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Up to approximately 115 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period | Day 0 (after start of study drug administration) through Day 364 (Week 52) | 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). |
| Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period | Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364 | 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). |
| Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | 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 | 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. |
| Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | 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 | 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). |
| Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | 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 | 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). |
| Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | 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 | 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). |
| Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | 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 | 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. |
| Number of Participants With HAE Attack-Free Status for Each Evaluation Period | 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 | 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). |
| Plasma Kallikrein (pKal) Activity | Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392 | pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics of lanadelumab. |
| Number of Participants With Immunogenicity Status as Positive or Negative | Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392 | Immunogenicity was measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma. |
Countries
Canada, Germany, Hungary, Spain, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 4 |
| 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. | 17 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period A (Weeks 1 to 26) | Withdrawal by Parent/Guardian | 1 | 0 |
Baseline characteristics
| Characteristic | Lanadelumab 150 mg: Age 6 to <12 Years | Total | Lanadelumab 150 mg: Age 2 to <6 Years |
|---|---|---|---|
| Age, Continuous | 8.68 years STANDARD_DEVIATION 1.391 | 7.88 years STANDARD_DEVIATION 2.134 | 4.45 years STANDARD_DEVIATION 0.843 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 19 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 20 Participants | 4 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 18 |
| other Total, other adverse events | 6 / 11 | 15 / 18 |
| serious Total, serious adverse events | 0 / 11 | 0 / 18 |
Outcome results
Primary
Apparent Clearance (CL/F) of Lanadelumab
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Apparent Clearance (CL/F) of Lanadelumab | 0.00906 L/h | Geometric Coefficient of Variation 34 |
| Lanadelumab 150 mg, q2wks | Apparent Clearance (CL/F) of Lanadelumab | 0.0135 L/h | Geometric Coefficient of Variation 37.8 |
Primary
Apparent Volume of Distribution (V/F) of Lanadelumab
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Apparent Volume of Distribution (V/F) of Lanadelumab | 3.63 L | Geometric Coefficient of Variation 25.9 |
| Lanadelumab 150 mg, q2wks | Apparent Volume of Distribution (V/F) of Lanadelumab | 5.59 L | Geometric Coefficient of Variation 39.2 |
Primary
Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma | 464 μg.day/mL | Geometric Coefficient of Variation 37.7 |
Primary
Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma | 24.6 μg/mL | Geometric Coefficient of Variation 34 |
| Lanadelumab 150 mg, q2wks | Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma | 33.2 μg/mL | Geometric Coefficient of Variation 37.7 |
Primary
Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma | 39.0 micrograms per mL (μg/mL) | Geometric Coefficient of Variation 39.2 |
Primary
Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma | 11.1 µg/mL | Geometric Coefficient of Variation 46.5 |
| Lanadelumab 150 mg, q2wks | Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma | 24.8 µg/mL | Geometric Coefficient of Variation 37.3 |
Primary
Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion.
Time frame: Up to approximately 115 weeks
Population: The Safety Analysis Set consisted of all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 150 mg, q4wks | Number of Participants With Clinically Significant Laboratory Assessment Abnormalities | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Clinically Significant Laboratory Assessment Abnormalities | 0 Participants |
Primary
Number of Participants With Clinically Significant Vital Signs Measurements
Vital signs included blood pressure, heart rate, body temperature, and respiratory rate.
Time frame: Up to approximately 115 weeks
Population: The Safety Analysis Set consisted of all participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 150 mg, q4wks | Number of Participants With Clinically Significant Vital Signs Measurements | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Clinically Significant Vital Signs Measurements | 0 Participants |
Primary
Plasma Concentrations of Lanadelumab Over The Treatment Period
The plasma concentration of lanadelumab over treatment period was assessed.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 8 Day 56 | 10433.382 nanograms per milliliter (ng/mL) | Standard Deviation 3345.1718 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 24 Day 168 | 12189.214 nanograms per milliliter (ng/mL) | Standard Deviation 11367.4241 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 2 Day 4 | 32407.215 nanograms per milliliter (ng/mL) | Standard Deviation 9785.4332 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 26 Day 182 | 25630.909 nanograms per milliliter (ng/mL) | Standard Deviation 11054.3701 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 12 Day 84 | 14758.407 nanograms per milliliter (ng/mL) | Standard Deviation 8392.862 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 28 Day 196 | 14293.013 nanograms per milliliter (ng/mL) | Standard Deviation 6014.0384 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 4 Day 28 | 10636.682 nanograms per milliliter (ng/mL) | Standard Deviation 6168.5347 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 36 Day 252 | 23110.526 nanograms per milliliter (ng/mL) | Standard Deviation 18241.5743 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 16 Day 112 | 15020.780 nanograms per milliliter (ng/mL) | Standard Deviation 5730.4397 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 44 Day 308 | 22687.442 nanograms per milliliter (ng/mL) | Standard Deviation 20911.9442 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 3 Day 14 | 20443.818 nanograms per milliliter (ng/mL) | Standard Deviation 7800.4019 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 52 Day 364 | 27178.967 nanograms per milliliter (ng/mL) | Standard Deviation 24111.9243 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 20 Day 140 | 13318.715 nanograms per milliliter (ng/mL) | Standard Deviation 4432.0728 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 1 Day 0 | 0.000 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 56 Day 392 (End of Study Visit) | 15689.458 nanograms per milliliter (ng/mL) | Standard Deviation 11811.7412 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 1 Day 0 | 11.735 nanograms per milliliter (ng/mL) | Standard Deviation 39.2984 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 2 Day 4 | 20349.609 nanograms per milliliter (ng/mL) | Standard Deviation 12587.7085 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 3 Day 14 | 14589.883 nanograms per milliliter (ng/mL) | Standard Deviation 4734.4461 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 4 Day 28 | 21198.858 nanograms per milliliter (ng/mL) | Standard Deviation 8378.3961 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 8 Day 56 | 27751.659 nanograms per milliliter (ng/mL) | Standard Deviation 10048.7527 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 12 Day 84 | 24895.121 nanograms per milliliter (ng/mL) | Standard Deviation 11852.7671 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 16 Day 112 | 31053.260 nanograms per milliliter (ng/mL) | Standard Deviation 14012.6464 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 20 Day 140 | 26534.885 nanograms per milliliter (ng/mL) | Standard Deviation 11234.6051 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 24 Day 168 | 26166.340 nanograms per milliliter (ng/mL) | Standard Deviation 11070.0337 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 26 Day 182 | 25372.349 nanograms per milliliter (ng/mL) | Standard Deviation 8242.4858 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 28 Day 196 | 25238.600 nanograms per milliliter (ng/mL) | Standard Deviation 9921.4264 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 36 Day 252 | 19058.886 nanograms per milliliter (ng/mL) | Standard Deviation 12079.1976 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 44 Day 308 | 15774.463 nanograms per milliliter (ng/mL) | Standard Deviation 12043.0984 |
| Lanadelumab 150 mg, q2wks | Plasma Concentrations of Lanadelumab Over The Treatment Period | Visit 52 Day 364 | 17239.653 nanograms per milliliter (ng/mL) | Standard Deviation 11975.4861 |
Primary
Terminal Half-life (t1/2) of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab 150 mg, q4wks | Terminal Half-life (t1/2) of Lanadelumab in Plasma | 11.7 days |
| Lanadelumab 150 mg, q2wks | Terminal Half-life (t1/2) of Lanadelumab in Plasma | 12.6 days |
Primary
Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab 150 mg, q4wks | Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma | 122 hours (h) |
| Lanadelumab 150 mg, q2wks | Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma | 86.0 hours (h) |
Secondary
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | Treatment Period B | 0.06 HAE attacks per month | Standard Deviation 0.132 |
| Lanadelumab 150 mg, q2wks | Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | Overall Treatment Period | 0.07 HAE attacks per month | Standard Deviation 0.14 |
| Lanadelumab 150 mg, q2wks | Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | Overall Presumed Steady-state Period | 0.06 HAE attacks per month | Standard Deviation 0.126 |
| Lanadelumab 150 mg, q2wks | Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | Treatment Period A | 0.07 HAE attacks per month | Standard Deviation 0.175 |
| Lanadelumab 150 mg, q2wks | Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | Presumed Steady-state Period for Treatment Period A | 0.04 HAE attacks per month | Standard Deviation 0.135 |
Secondary
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B | 0.01 HAE attacks per month | Standard Deviation 0.039 |
| Lanadelumab 150 mg, q2wks | 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 0.039 |
| Lanadelumab 150 mg, q2wks | Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Presumed Steady-state Period | 0.01 HAE attacks per month | Standard Deviation 0.039 |
| Lanadelumab 150 mg, q2wks | Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A | 0.00 HAE attacks per month | Standard Deviation 0 |
| Lanadelumab 150 mg, q2wks | Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Presumed Steady-state Period for Treatment Period A | 0.00 HAE attacks per month | Standard Deviation 0 |
Secondary
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period | Treatment Period B | 0.08 HAE attacks per month | Standard Deviation 0.142 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period | Overall Presumed Steady-state Period | 0.07 HAE attacks per month | Standard Deviation 0.143 |
| Lanadelumab 150 mg, q2wks | 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 | 0.06 HAE attacks per month | Standard Deviation 0.192 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period | Treatment Period A | 0.08 HAE attacks per month | Standard Deviation 0.207 |
Secondary
Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period | 0.07 HAE attacks per month | Standard Deviation 0.219 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period | 0.08 HAE attacks per month | Standard Deviation 0.157 |
Secondary
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B | 0.1 HAE attacks per month | Standard Deviation 0.13 |
| Lanadelumab 150 mg, q2wks | 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 0.144 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Presumed Steady-state Period | 0.06 HAE attacks per month | Standard Deviation 0.125 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A | 0.07 HAE attacks per month | Standard Deviation 0.175 |
| Lanadelumab 150 mg, q2wks | Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Steady-state Period for Treatment Period A | 0.04 HAE attacks per month | Standard Deviation 0.135 |
Secondary
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Rescue Medication Use: Icatibant | 0 Participants |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Rescue Medication Use: Icatibant | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Rescue Medication Use: Icatibant | 0 Participants |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q4wks | 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 |
| Lanadelumab 150 mg, q2wks | 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 | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 0 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: HAE Primary Attack Location: Peripheral | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: HAE Primary Attack Location: Abdominal | 4 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: HAE Attack Derived Location: Peripheral | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: HAE Attack Derived Location: Abdominal | 4 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Rescue Medication Use: No Use | 2 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Rescue Medication Use: Icatibant | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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) | 2 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: HAE Primary Attack Location: Peripheral | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: HAE Primary Attack Location: Abdominal | 4 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: HAE Attack Derived Location: Peripheral | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: HAE Attack Derived Location: Abdominal | 4 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Rescue Medication Use: No Use | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Rescue Medication Use: Icatibant | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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) | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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) | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 3 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 3 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Presumed Steady-state Period: Rescue Medication Use: Icatibant | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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) | 2 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Mean HAE attack duration: 0 hour | 14 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Mean HAE attack duration: <12 hours | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Maximum HAE attack severity: No attack | 14 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Maximum HAE attack severity: Moderate | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Maximum HAE attack severity: Severe | 0 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 15 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 15 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Mean HAE attack duration: 0 hour | 13 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 3 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Mean HAE attack duration: >48 hours | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Maximum HAE attack severity: No attack | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Maximum HAE attack severity: Moderate | 4 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period B: Maximum HAE attack severity: Severe | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Mean HAE attack duration: 0 hour | 13 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Maximum HAE attack severity: No attack | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Overall Treatment Period: Maximum HAE attack severity: Moderate | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | 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 | 13 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 13 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 4 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: HAE Primary Attack Location: Peripheral | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: HAE Attack Derived Location: Peripheral | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Rescue Medication Use: No Use | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | Treatment Period A: Rescue Medication Use: Icatibant | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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) | 1 Participants |
| Lanadelumab 150 mg, q2wks | 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 |
| Lanadelumab 150 mg, q2wks | 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 | 2 Participants |
| Lanadelumab 150 mg, q2wks | 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 | 0 Participants |
Secondary
Number of Participants With HAE Attack-Free Status for Each Evaluation Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Presumed Steady-state Period for Treatment Period A | 2 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Overall Treatment Period | 10 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Treatment Period B | 9 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Overall Presumed Steady-state Period | 9 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Treatment Period A | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Overall Presumed Steady-state Period | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Treatment Period A | 14 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Presumed Steady-state Period for Treatment Period A | 15 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Treatment Period B | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With HAE Attack-Free Status for Each Evaluation Period | Overall Treatment Period | 13 Participants |
Secondary
Number of Participants With Immunogenicity Status as Positive or Negative
Immunogenicity was measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Negative | 4 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Negative | 4 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Negative | 3 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Negative | 4 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Negative | 4 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q4wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive (Non-neutralizing) | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Negative | 17 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Baseline (Day 0): ADA Positive (Non-neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Negative | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Visit 4 Day 28: ADA Positive (Non-neutralizing) | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Negative | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive (Neutralizing) | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period A: ADA Positive (Non-neutralizing) | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Negative | 15 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive (Neutralizing) | 0 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive (Non-neutralizing) | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Negative | 13 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive | 3 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Study Period: ADA Positive (Neutralizing) | 1 Participants |
| Lanadelumab 150 mg, q2wks | Number of Participants With Immunogenicity Status as Positive or Negative | Overall Treatment Period B: ADA Positive | 1 Participants |
Secondary
Plasma Kallikrein (pKal) Activity
pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics of lanadelumab.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 8 Day 56 | 15.1333 percentage of cHMWK | Standard Deviation 12.95582 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 24 Day 168 | 21.9000 percentage of cHMWK | Standard Deviation 20.71545 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 2 Day 4 | 16.4000 percentage of cHMWK | Standard Deviation 8.94036 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 26 Day 182 | 17.9000 percentage of cHMWK | Standard Deviation 14.29021 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 12 Day 84 | 18.2333 percentage of cHMWK | Standard Deviation 17.91768 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 28 Day 196 | 9.2000 percentage of cHMWK | Standard Deviation 2.52389 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 4 Day 28 | 18.8500 percentage of cHMWK | Standard Deviation 14.15968 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 36 Day 252 | 15.2000 percentage of cHMWK | Standard Deviation 13.16397 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 16 Day 112 | 10.7333 percentage of cHMWK | Standard Deviation 5.48118 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 44 Day 308 | 13.5333 percentage of cHMWK | Standard Deviation 7.24316 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 3 Day 14 | 9.5750 percentage of cHMWK | Standard Deviation 4.0574 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 52 Day 364 | 10.7333 percentage of cHMWK | Standard Deviation 2.87112 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 20 Day 140 | 15.2000 percentage of cHMWK | Standard Deviation 16.96202 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 56 Day 392 EOS | 10.9000 percentage of cHMWK | Standard Deviation 3.15753 |
| Lanadelumab 150 mg, q4wks | Plasma Kallikrein (pKal) Activity | Visit 1 Day 0 | 30.2500 percentage of cHMWK | Standard Deviation 13.61017 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 56 Day 392 EOS | 19.4286 percentage of cHMWK | Standard Deviation 14.57677 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 1 Day 0 | 45.6438 percentage of cHMWK | Standard Deviation 25.7947 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 2 Day 4 | 32.2857 percentage of cHMWK | Standard Deviation 17.89606 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 3 Day 14 | 25.7176 percentage of cHMWK | Standard Deviation 11.75565 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 4 Day 28 | 26.1571 percentage of cHMWK | Standard Deviation 11.76616 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 8 Day 56 | 24.6267 percentage of cHMWK | Standard Deviation 14.28963 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 12 Day 84 | 24.7214 percentage of cHMWK | Standard Deviation 12.84339 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 16 Day 112 | 18.0000 percentage of cHMWK | Standard Deviation 11.05992 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 20 Day 140 | 16.3417 percentage of cHMWK | Standard Deviation 12.53841 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 24 Day 168 | 19.6167 percentage of cHMWK | Standard Deviation 16.61762 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 26 Day 182 | 18.6818 percentage of cHMWK | Standard Deviation 10.54332 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 28 Day 196 | 14.6571 percentage of cHMWK | Standard Deviation 7.29939 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 36 Day 252 | 16.3067 percentage of cHMWK | Standard Deviation 10.26008 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 44 Day 308 | 23.2750 percentage of cHMWK | Standard Deviation 15.23577 |
| Lanadelumab 150 mg, q2wks | Plasma Kallikrein (pKal) Activity | Visit 52 Day 364 | 14.4733 percentage of cHMWK | Standard Deviation 8.51448 |
Secondary
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lanadelumab 150 mg, q4wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Presumed Steady-state Period for Treatment Period A | NA days |
| Lanadelumab 150 mg, q4wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Overall Treatment Period | NA days |
| Lanadelumab 150 mg, q4wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Treatment Period B | NA days |
| Lanadelumab 150 mg, q4wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Overall Presumed Steady-state Period | NA days |
| Lanadelumab 150 mg, q4wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Treatment Period A | NA days |
| Lanadelumab 150 mg, q2wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Overall Presumed Steady-state Period | NA days |
| Lanadelumab 150 mg, q2wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Treatment Period A | NA days |
| Lanadelumab 150 mg, q2wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Presumed Steady-state Period for Treatment Period A | NA days |
| Lanadelumab 150 mg, q2wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Treatment Period B | NA days |
| Lanadelumab 150 mg, q2wks | Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | Overall Treatment Period | NA days |