Hereditary Angioedema (HAE)
Conditions
Brief summary
The purpose of this phase 3, open-label, multi-center study is to evaluate the safety and efficacy of lanadelumab in Japanese participants with HAE Type I or II.
Detailed description
This study will consist of 52-week treatment period and a 4-week follow-up period. 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. After completion of treatment period B participants may roll over into an expanded access study TAK-743-5007 (NCT04687137). Participants who elect to rollover to Study TAK-743-5007 will complete their end of study (EOS) assessments on Day 378. All other participants will complete their EOS assessments on Day 392.
Interventions
DRUGLanadelumab
Lanadelumab solution, SC
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents. * The participant is male or female and \>= 12 years of age at the time of informed consent. * Documented diagnosis of HAE (Type I or II) based upon all of the following: 1. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria). 2. Diagnostic testing results obtained during screening that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level \<40% of the normal level. Participants with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. With prior sponsor approval, participants may be retested during the run-in period if results are in congruent with clinical history or believed by the investigator to be confounded by recent C1 inhibitor use. 3. At least one of the following: age at reported onset of first angioedema symptoms \<=30 years, a family history consistent with HAE Type I or II, or C1q within normal range. * Attack rate: Participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period to enter the lanadelumab treatment period. * The participant (or the participants parent/legal authorized representative, if applicable) has provided written informed consent approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). * If the participant is an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed or if the participant is a minor (ie, below the age of majority), have a parent/legally authorized representative who is informed of the nature of the study provide written informed consent (ie, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants. * Males, or non pregnant, non lactating females who are fertile and sexually active and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study, or females of non child bearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or postmenopausal for at least 12 months. * Agree to adhere to the protocol-defined schedule of assessments and procedures.
Exclusion criteria
* Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH (also known as HAE Type 3), idiopathic angioedema, or recurrent angioedema associated with urticaria. * Participation in a prior lanadelumab study. * Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening. * Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening. * Exposure to androgens (eg, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period. * Use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) within 2 weeks prior to entering the run in period. * Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or anti-fibrinolytics used to avoid angioedema complications from medically indicated procedures. * Any of the following liver function abnormalities: alanine aminotransferase (ALT) \>3x upper limit of normal, or aspartate aminotransferase (AST) \>3x upper limit of normal or bilirubin \>2x upper limit of normal (unless the bilirubin is a result of Gilbert's syndrome). * Pregnancy or breast feeding. * Participant has any condition that in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (eg, history of substance abuse, or dependence, significant preexisting illnesses or major comorbidity the investigator considers may confound the interpretation of the study results). * Participant has a known hypersensitivity to the IP or its components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed hereditary angioedema (HAE) attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants achieving attack-free status for the efficacy evaluation period of Day 0 through Day 182 were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of investigator-confirmed HAE attacks requiring acute treatment during each of the efficacy evaluation periods were assessed. |
| Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | Severe attack was defined as Grade 3 (some assistance usually required, medical intervention/therapy required, hospitalizations possible), moderate attack was defined as Grade 2 (some assistance may be needed, no or minimal medical intervention/therapy required). Number of investigator-confirmed moderate or severe HAE attacks during the each of efficacy evaluation periods was assessed. Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. |
| Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of participants with maximum HAE attack severity during each of the efficacy evaluation periods was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. |
| Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | A high morbidity HAE attack was defined as any attack that has at least 1 of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic blood pressure \<90, requires intravenous (IV) hydration, or associated with syncope or near syncope) or laryngeal. Number of high-morbidity investigator-confirmed HAE attacks during each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A and Overall Presumed Steady-state Period) were assessed. |
| Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period | Day 0 through Day 182 | The time to the first HAE attack (days) after Day 0 for the efficacy evaluation period of Day 0 through Day 182 was calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 0 through Day 182) to the date and time of the first in HAE attack after the first open-label dose for the efficacy evaluation period of Day 0 through Day 182. Kaplan-Meier Method was used for analysis and the Kaplan Meier estimate expressed as time (in days) to first HAE attack After Day 0 for Treatment Period A (Day 0 through Day 182) is presented. |
| Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | Run- in Period was 4 weeks and may have been extended up to 8 weeks to determine participants' Baseline attack rate. The normalized number of investigator-confirmed HAE attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) HAE attack rate. Number of participants achieving at least 50%, 70% and 90% reduction in the investigator-confirmed NNA per 4 weeks relative to the Run-in Period normalized NNA for each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. For each participant, the percentage reduction was calculated as the run-in period attack rate minus the treatment period attack rate divided by the run-in period attack rate, multiplied by 100. The responder categories were not mutually exclusive, participants may appear in more than one category as applicable based on their percentage reduction. |
| Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | The NNA (investigator-confirmed) during each efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate. Number of participants achieving NNA \<1.0 per 4 weeks, \<0.75 per 4 weeks, \<0.50 per 4 weeks, and \<0.25 per 4 weeks for each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. The responder categories were not mutually exclusive, participants may appear in more than one category as applicable based on their HAE attack rate. |
| Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364 | Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364 | A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed HAE attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants achieving attack-free status for the 4 efficacy evaluation periods (Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. |
| Number of Participants Achieving Attack-Free Status for Monthly Increments | At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13 | A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed HAE attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). |
| Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of investigator-confirmed HAE attacks during each of the efficacy evaluation periods were assessed. |
| Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 | An attack-free day was defined as a calendar day with no investigator-confirmed HAE attack. HAE attack free days were calculated by counting the number of days in the efficacy evaluation period without an HAE attack and dividing by the number of days the participant contributed to the efficacy evaluation period. Percentage of investigator-confirmed HAE attack free days during each of the efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | From first dose of the study drug up to end of study (EOS) (up to Day 392) | TEAE=any event emerging at or after initiation of treatment with investigational product (IP) or any existing event that worsens in intensity/frequency on exposure to IP. Serious TEAE=any untoward clinical manifestation of signs, symptoms, outcomes (related to IP or not) at any dose: results in death, was life-threatening, requires inpatient/prolongation of hospitalization, resulted in persistent/significant disability/incapacity, congenital abnormality/birth defect, important medical event. AESI=investigator-reported hypersensitivity reactions, events of disordered coagulation as bleeding/hypercoagulable AESI. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly. As Pre-specified in the protocol, TEAEs, SAEs and AESIs were collected per Period i.e., Treatment Period A, B and Safety follow-up Period and data is reported accordingly. |
| Plasma Concentrations of Lanadelumab | Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 | — |
| Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392 | The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema (including HAE). The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items had a five-point response scale ranging from 1 (Never) to 5 (Very Often). The questionnaire was scored according to the developers' guidelines to produce 4 domain scores (functioning, fatigue/mood, fear/shame, nutrition) yielding a total score. The raw total score (mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0 to 100, based on the maximum possible score, where higher the score, greater the QoL impairment. |
| Plasma Kallikrein (pKal) Activity | Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 | pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics (PD) of lanadelumab. |
| Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 | Baseline was defined as the last non-missing value prior to first dose of study drug (based on date or date/time). |
| Number of Participants With TEAEs Related to Clinical Laboratory Tests | From first dose of the study drug up to end of study (EOS) (up to Day 392) | A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to clinical laboratory tests (hematology, clinical chemistry, coagulation, and urinalysis) were assessed. |
| Number of Participants With TEAEs Related to Vital Signs | From first dose of the study drug up to end of study (EOS) (up to Day 392) | A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to vital signs (blood pressure (BP), heart rate (HR), body temperature, and respiratory rate) were assessed. |
| Number of Participants With TEAEs Related to Electrocardiogram (ECG) | From first dose of the study drug up to end of study (EOS) (up to Day 392) | A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to 12 lead-ECG were assessed. |
| Number of Participants Achieving Investigator-Confirmed Hereditary Angioedema (HAE) Attack-Free Intervals | Day 0 through Day 182 | A participant was considered as attack free during a time period if the participant had no investigator-confirmed HAE attacks during that time period. Participants who discontinued during a time period were considered as non-responders for that time period. Number of participants achieving investigator-confirmed HAE attack free intervals from Day 0 through Day 182 were assessed. |
Countries
Japan
Participant flow
Recruitment details
A total of 12 participants took part in the study at 10 investigative sites in Japan from 12 December 2019 to 26 August 2021.
Pre-assignment details
Enrolled participants were observed in 4-week Baseline Run-in Period that could be extended up to 8 weeks. Participants who experienced ≥1.0 angioedema attacks per 4 weeks during the Run-in Period and who remained eligible per inclusion criteria entered 52-week lanadelumab Treatment Period (Treatment Period A + Treatment Period B), followed by up to 4-week Safety Follow-up Period. Participants received lanadelumab only during the Treatment Periods.
Participants by arm
| Arm | Count |
|---|---|
| Lanadelumab 300 mg q2w or q4w Lanadelumab 300 mg solution, SC, q2w for 26 weeks in Treatment Period A. This was followed by Treatment Period B (additional 26 weeks, total of 52 weeks including Treatment Period A) during which participants remained on Treatment Period A regimen or received 300 mg lanadelumab solution q4w for 26 weeks if well-controlled (attack-free) for 26 consecutive weeks with lanadelumab treatment. The dose frequency change was based on the Investigator's discretion and approval by the Sponsor's Medical Monitor. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Lanadelumab 300 mg q2w or q4w |
|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 12.36 |
| Body Mass Index (BMI) | 23.80 kg/m^2 STANDARD_DEVIATION 5.065 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 161.08 cm STANDARD_DEVIATION 9.379 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 12 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight | 61.24 kg STANDARD_DEVIATION 10.346 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 10 / 12 | 7 / 12 | 9 / 12 | 8 / 12 | 0 / 12 | 3 / 12 |
| serious Total, serious adverse events | 1 / 12 | 1 / 12 | 1 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182
A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed hereditary angioedema (HAE) attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants achieving attack-free status for the efficacy evaluation period of Day 0 through Day 182 were assessed.
Time frame: Day 0 through Day 182
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182 | 5 Participants |
Secondary
Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema (including HAE). The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items had a five-point response scale ranging from 1 (Never) to 5 (Very Often). The questionnaire was scored according to the developers' guidelines to produce 4 domain scores (functioning, fatigue/mood, fear/shame, nutrition) yielding a total score. The raw total score (mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0 to 100, based on the maximum possible score, where higher the score, greater the QoL impairment.
Time frame: Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 154 | 21.69 score on a scale | Standard Deviation 28.75 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 0 | 46.57 score on a scale | Standard Deviation 20.885 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 28 | 26.35 score on a scale | Standard Deviation 31.129 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 56 | 28.43 score on a scale | Standard Deviation 28.255 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 98 | 26.96 score on a scale | Standard Deviation 30.926 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 126 | 32.60 score on a scale | Standard Deviation 33.999 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 182 | 26.10 score on a scale | Standard Deviation 33.978 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 266 | 26.96 score on a scale | Standard Deviation 29.951 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 364 | 26.59 score on a scale | Standard Deviation 34.428 |
| Lanadelumab 300 mg q2w or q4w | Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score | Day 378/392 | 28.55 score on a scale | Standard Deviation 31.934 |
Secondary
Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
A high morbidity HAE attack was defined as any attack that has at least 1 of the following characteristics: severe, results in hospitalization (except hospitalization for observation \<24 hours), hemodynamically significant (systolic blood pressure \<90, requires intravenous (IV) hydration, or associated with syncope or near syncope) or laryngeal. Number of high-morbidity investigator-confirmed HAE attacks during each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A and Overall Presumed Steady-state Period) were assessed.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182 | 5 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364 | 11 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182 | 4 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364 | 10 HAE attacks |
Secondary
Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of investigator-confirmed HAE attacks during each of the efficacy evaluation periods were assessed.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182 | 92 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364 | 189 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182 | 55 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364 | 152 HAE attacks |
Secondary
Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods
Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of investigator-confirmed HAE attacks requiring acute treatment during each of the efficacy evaluation periods were assessed.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364 | 168 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182 | 46 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182 | 79 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364 | 135 HAE attacks |
Secondary
Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
Severe attack was defined as Grade 3 (some assistance usually required, medical intervention/therapy required, hospitalizations possible), moderate attack was defined as Grade 2 (some assistance may be needed, no or minimal medical intervention/therapy required). Number of investigator-confirmed moderate or severe HAE attacks during the each of efficacy evaluation periods was assessed. Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364 | 153 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364 | 122 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182 | 72 HAE attacks |
| Lanadelumab 300 mg q2w or q4w | Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182 | 41 HAE attacks |
Secondary
Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods
Run- in Period was 4 weeks and may have been extended up to 8 weeks to determine participants' Baseline attack rate. The normalized number of investigator-confirmed HAE attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) HAE attack rate. Number of participants achieving at least 50%, 70% and 90% reduction in the investigator-confirmed NNA per 4 weeks relative to the Run-in Period normalized NNA for each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. For each participant, the percentage reduction was calculated as the run-in period attack rate minus the treatment period attack rate divided by the run-in period attack rate, multiplied by 100. The responder categories were not mutually exclusive, participants may appear in more than one category as applicable based on their percentage reduction.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 182: ≥50% Reduction | 10 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 182: ≥70% Reduction | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 182: ≥90% Reduction | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 364: ≥50% Reduction | 10 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 364: ≥70% Reduction | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 0 Through Day 364: ≥90% Reduction | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 182: ≥50% Reduction | 11 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 182: ≥70% Reduction | 10 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 182: ≥90% Reduction | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 364: ≥50% Reduction | 10 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 364: ≥70% Reduction | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods | Day 70 Through Day 364: ≥90% Reduction | 7 Participants |
Secondary
Number of Participants Achieving Attack-Free Status for Monthly Increments
A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed HAE attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Time frame: At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 1 | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 2 | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 3 | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 4 | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 5 | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 6 | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 7 | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 8 | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 9 | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 10 | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 11 | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 12 | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for Monthly Increments | Month 13 | 8 Participants |
Secondary
Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364
A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed HAE attacks during that efficacy evaluation period. A HAE attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants achieving attack-free status for the 4 efficacy evaluation periods (Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed.
Time frame: Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP. Overall number analyzed are the number of participants who achieved attack-free status during an efficacy evaluation period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364 | Day 0 Through Day 364 | 2 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364 | Day 70 Through Day 182 | 5 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364 | Day 70 Through Day 364 | 2 Participants |
Secondary
Number of Participants Achieving Investigator-Confirmed Hereditary Angioedema (HAE) Attack-Free Intervals
A participant was considered as attack free during a time period if the participant had no investigator-confirmed HAE attacks during that time period. Participants who discontinued during a time period were considered as non-responders for that time period. Number of participants achieving investigator-confirmed HAE attack free intervals from Day 0 through Day 182 were assessed.
Time frame: Day 0 through Day 182
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Investigator-Confirmed Hereditary Angioedema (HAE) Attack-Free Intervals | 5 Participants |
Secondary
Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods
The NNA (investigator-confirmed) during each efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate. Number of participants achieving NNA \<1.0 per 4 weeks, \<0.75 per 4 weeks, \<0.50 per 4 weeks, and \<0.25 per 4 weeks for each of the 4 efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed. The responder categories were not mutually exclusive, participants may appear in more than one category as applicable based on their HAE attack rate.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: <1.0 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: <0.75 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: <0.50 per Month | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: <0.25 per Month | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: <1.0 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: <0.75 per Month | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: <0.50 per Month | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: <0.25 per Month | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: <1.0 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: <0.75 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: <0.50 per Month | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: <0.25 per Month | 6 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: <1.0 per Month | 9 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: <0.75 per Month | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: <0.50 per Month | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: <0.25 per Month | 6 Participants |
Secondary
Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods
Efficacy evaluation period consisted of four periods: Day 0 (after study drug administration) through Day 182 (the end of Treatment Period A), Day 0 (after study drug administration) through Day 364 (the end of Treatment Period B), presumed steady-state period from Day 70 through Day 182, presumed steady-state period from Day 70 through Day 364. Number of participants with maximum HAE attack severity during each of the efficacy evaluation periods was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: Moderate | 4 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: Moderate | 7 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: Severe | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: No Attack | 5 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: Mild | 2 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182: Severe | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: No Attack | 2 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: Mild | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: Moderate | 8 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364: Severe | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: No Attack | 5 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: Mild | 4 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: Moderate | 2 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182: Severe | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: No Attack | 2 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364: Mild | 2 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma
Baseline was defined as the last non-missing value prior to first dose of study drug (based on date or date/time).
Time frame: Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
Population: FAS included all participants who received at least 1 dose of IMP. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 140 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 182 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 266 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 0 (or Baseline) | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 56 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 98 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 350 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 364 | 0 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma | Day 378/392 | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Clinical Laboratory Tests
A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to clinical laboratory tests (hematology, clinical chemistry, coagulation, and urinalysis) were assessed.
Time frame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| Treatment Period A: HAE | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| Treatment Period B: Non-HAE | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| Treatment Period B: HAE | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| Safety Follow-up Period: HAE | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Electrocardiogram (ECG)
A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to 12 lead-ECG were assessed.
Time frame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| Treatment Period A: HAE | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| Treatment Period B: Non-HAE | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| Treatment Period B: HAE | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
| Safety Follow-up Period: HAE | Number of Participants With TEAEs Related to Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Vital Signs
A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. As Pre-specified in the protocol, the treatment emergent adverse events were collected per Period i.e., Treatment Period A, B and Safety follow-up Period. The data is reported as per HAE attack and non-HAE attack per Period. Number of participants with TEAEs related to vital signs (blood pressure (BP), heart rate (HR), body temperature, and respiratory rate) were assessed.
Time frame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| Treatment Period A: HAE | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| Treatment Period B: Non-HAE | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| Treatment Period B: HAE | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| Safety Follow-up Period: HAE | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs)
TEAE=any event emerging at or after initiation of treatment with investigational product (IP) or any existing event that worsens in intensity/frequency on exposure to IP. Serious TEAE=any untoward clinical manifestation of signs, symptoms, outcomes (related to IP or not) at any dose: results in death, was life-threatening, requires inpatient/prolongation of hospitalization, resulted in persistent/significant disability/incapacity, congenital abnormality/birth defect, important medical event. AESI=investigator-reported hypersensitivity reactions, events of disordered coagulation as bleeding/hypercoagulable AESI. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly. As Pre-specified in the protocol, TEAEs, SAEs and AESIs were collected per Period i.e., Treatment Period A, B and Safety follow-up Period and data is reported accordingly.
Time frame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 3 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 1 Participants |
| Lanadelumab 300 mg q2w or q4w | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 10 Participants |
| Treatment Period A: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 0 Participants |
| Treatment Period A: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 1 Participants |
| Treatment Period A: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 8 Participants |
| Treatment Period B: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 1 Participants |
| Treatment Period B: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 9 Participants |
| Treatment Period B: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 0 Participants |
| Treatment Period B: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 8 Participants |
| Treatment Period B: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 0 Participants |
| Treatment Period B: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 0 Participants |
| Safety Follow-up Period: Non-HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 0 Participants |
| Safety Follow-up Period: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | AESI | 0 Participants |
| Safety Follow-up Period: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any TEAEs | 3 Participants |
| Safety Follow-up Period: HAE | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | Any Serious TEAEs | 0 Participants |
Secondary
Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods
An attack-free day was defined as a calendar day with no investigator-confirmed HAE attack. HAE attack free days were calculated by counting the number of days in the efficacy evaluation period without an HAE attack and dividing by the number of days the participant contributed to the efficacy evaluation period. Percentage of investigator-confirmed HAE attack free days during each of the efficacy evaluation periods (Treatment Period A, Overall Treatment Period, Presumed Steady-state Period for Treatment Period A, and Overall Presumed Steady-state Period) were assessed.
Time frame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods | Day 0 Through Day 364 | 89.04 percentage of attack-free days | Standard Deviation 27.015 |
| Lanadelumab 300 mg q2w or q4w | Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods | Day 0 Through Day 182 | 88.53 percentage of attack-free days | Standard Deviation 27.146 |
| Lanadelumab 300 mg q2w or q4w | Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods | Day 70 Through Day 182 | 90.34 percentage of attack-free days | Standard Deviation 21.952 |
| Lanadelumab 300 mg q2w or q4w | Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods | Day 70 Through Day 364 | 89.85 percentage of attack-free days | Standard Deviation 25.015 |
Secondary
Plasma Concentrations of Lanadelumab
Time frame: Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
Population: Pharmacokinetic (PK) Set included all participants in the FAS who had at least 1 evaluable post dose PK concentration value. Number analyzed is the number of participants available for analysis at a specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 0 | 25.584 nanograms per milliliter (ng/mL) | Standard Deviation 50.2034 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 56 | 23630.973 nanograms per milliliter (ng/mL) | Standard Deviation 8665.1099 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 98 | 24142.776 nanograms per milliliter (ng/mL) | Standard Deviation 9575.7596 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 140 | 24613.885 nanograms per milliliter (ng/mL) | Standard Deviation 9319.6672 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 182 | 23679.526 nanograms per milliliter (ng/mL) | Standard Deviation 6793.3003 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 266 | 19269.249 nanograms per milliliter (ng/mL) | Standard Deviation 8870.0355 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 350 | 13225.533 nanograms per milliliter (ng/mL) | Standard Deviation 2538.8239 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 364 | 22329.820 nanograms per milliliter (ng/mL) | Standard Deviation 7527.7165 |
| Lanadelumab 300 mg q2w or q4w | Plasma Concentrations of Lanadelumab | Day 378/392 | 19308.033 nanograms per milliliter (ng/mL) | Standard Deviation 7708.1882 |
Secondary
Plasma Kallikrein (pKal) Activity
pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics (PD) of lanadelumab.
Time frame: Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
Population: Pharmacodynamic (PD) Set included all participants in the FAS who had at least 1 evaluable post dose PD value. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 0 | 63.04 percentage of cHMWK | Standard Deviation 22.096 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 56 | 30.88 percentage of cHMWK | Standard Deviation 17.09 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 98 | 32.40 percentage of cHMWK | Standard Deviation 18.829 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 140 | 35.67 percentage of cHMWK | Standard Deviation 13.787 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 182 | 30.31 percentage of cHMWK | Standard Deviation 17.344 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 266 | 21.69 percentage of cHMWK | Standard Deviation 11.221 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 350 | 39.83 percentage of cHMWK | Standard Deviation 12.407 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 364 | 27.51 percentage of cHMWK | Standard Deviation 12.901 |
| Lanadelumab 300 mg q2w or q4w | Plasma Kallikrein (pKal) Activity | Day 378/392 | 40.65 percentage of cHMWK | Standard Deviation 15.828 |
Secondary
Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period
The time to the first HAE attack (days) after Day 0 for the efficacy evaluation period of Day 70 through Day 182 was calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 70 through Day 182) to the date and time of the first in HAE attack after the first open-label dose for the efficacy evaluation period of Day 70 through Day 182. Kaplan-Meier Method was used for analysis and the Kaplan Meier estimate expressed as time (in days) to first HAE attack After Day 0 for presumed steady-state period for Treatment Period A (Day 70 through Day 182) is presented.
Time frame: Day 70 through Day 182
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period | 91.0 days |
Secondary
Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period
The time to the first HAE attack (days) after Day 0 for the efficacy evaluation period of Day 0 through Day 182 was calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 0 through Day 182) to the date and time of the first in HAE attack after the first open-label dose for the efficacy evaluation period of Day 0 through Day 182. Kaplan-Meier Method was used for analysis and the Kaplan Meier estimate expressed as time (in days) to first HAE attack After Day 0 for Treatment Period A (Day 0 through Day 182) is presented.
Time frame: Day 0 through Day 182
Population: FAS included all participants who received at least 1 dose of IMP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period | 97.2 days |