Hereditary Angioedema (HAE)
Conditions
Brief summary
The main aim of this study is to evaluate the safety of lanadelumab in Chinese participants with HAE. Participants will be treated with lanadelumab for 26 weeks.
Interventions
DRUGLanadelumab
Lanadelumab subcutaneous injection
Sponsors
Takeda
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
1. Be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents. 2. The participant is male or female and greater than or equal to (\>=) 12 years of age at the time of informed consent. 3. Documented diagnosis of HAE Type I or Type II based upon all of the following: * Documented clinical history consistent with HAE (subcutaneous \[SC\] or mucosal, nonpruritic swelling episodes without accompanying urticaria). * Diagnostic testing results obtained during screening by a laboratory (approved by the sponsor) that confirm HAE Type I or Type II: C1 esterase inhibitor (C1-INH) functional level \<40% of the normal level. Participants with functional C1-INH level 40% to 50% of the normal level may be enrolled if they also have a C4 level below the normal range. Participants may begin participating in the run-in period before these diagnostic results are available. Participants may be re-tested if results are incongruent with clinical history or believed by the investigator to be confounded by recent long-term prophylaxis (LTP) use. * At least one of the following: Age at reported onset of first angioedema symptoms less than or equal to (\<=) 30 years, a family history consistent with HAE Type I or Type II, or C1q within normal range. 4. Attack rate: • At the time of enrollment, participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period. 5. The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board (IRB)/ institutional ethical committee (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 (that is \<18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (that is, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants. 6. 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-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or postmenopausal for at least 12 months. 7. Agree to adhere to the protocol-defined schedule of assessments and procedures.
Exclusion criteria
1. Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema, HAE with normal C1 esterase inhibitor (C1-INH) (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria. 2. Participation in a prior lanadelumab study or use any lanadelumab prior to the study. 3. Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening. 4. Exposure to angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening. 5. Exposure to androgens (that is, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period. 6. Use of LTP therapy (defined as continued use) for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) for adult participants within 2 weeks prior to entering the run-in period. Adolescent participants (\>=12 to \<18 years of age) who are on LTP therapy for HAE are allowed to enter the study. 7. Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as fresh frozen plasma (FFP), C1-INH, attenuated androgens, or antifibrinolytics used to avoid angioedema complications from medically indicated procedures. Note: Currently, C1-INH therapies are not available in China. 8. Any of the following liver function abnormalities: alanine aminotransferase (ALT) greater than (\>) 3\* upper limit of normal (ULN), or aspartate aminotransferase (AST) \> 3\* ULN or bilirubin \> 2\* ULN (unless the bilirubin is a result of Gilbert's syndrome). 9. Pregnancy or breast feeding. 10. 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 (example, history of substance abuse or dependence, significant pre-existing illnesses or major comorbidity the investigator considers may confound the interpretation of the study results).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | From first dose of study drug up to end of study (up to Day 210) | TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An SAE is any untoward clinical manifestation of signs, symptoms or outcomes whether considered related to investigational product or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category. |
| Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters | From first dose of study drug up to end of study (up to Day 210) | Laboratory parameters included clinical chemistry, hematology, coagulation, urinalysis, and serology. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters (including clinical chemistry, hematology, coagulation, urinalysis, and serology) were reported. |
| Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities | From first dose of study drug up to end of study (up to Day 210) | Vital signs included measurement of blood pressure, heart rate, body temperature, and respiratory rate. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in vital signs were reported. |
| Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | From first dose of study drug up to end of study (up to Day 210) | ECG included heart rate, PR interval, QRS duration, QT interval, corrected QT interval (QTc) interval, QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval, and QT corrected for heart rate by Bazett formula (QTcB) interval. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in ECG were reported. |
| Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182 | Day 182 | Physical examination findings by body system were classified as height and weight, general appearance, ears, nose and throat, head and neck, ophthalmological, respiratory, cardiovascular, abdomen, neurological, extremities, dermatological, and lymphatic. Number of participants with clinically significant changes in physical examination findings per investigator interpretation were reported. Only categories with at least one participant with event are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | Number of participants with maximum HAE attack severity during the efficacy evaluation period was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. |
| Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | Time to the first investigator-confirmed HAE attack (days) was calculated from the date and time of the first dose of study drug for that efficacy evaluation period to the date and time of the first investigator-confirmed HAE attack after the first dose for the efficacy evaluation period. The time to the first HAE attack was summarized using Kaplan-Meier (KM) estimates. |
| Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. A participant was considered as attack free if the participant had no investigator-confirmed HAE attacks during the efficacy evaluation period. Number of participants who achieved attack-free status for the efficacy evaluation periods were assessed. |
| Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA | Day 0 through Day 182 | A run-in period of 4 weeks was included to determine the participant's baseline attack rate. This period may be extended up to 8 weeks. The normalized number of investigator-confirmed HAE attacks during efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate relative to the run-in period NNA. Number of participants who achieved at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed NNA per 4 weeks relative to the run-in period normalized NNA for the efficacy evaluation periods was assessed. |
| Plasma Concentrations of Lanadelumab | Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 | — |
| Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 | Number of participants with neutralizing or non-neutralizing ADA in plasma were assessed. |
| Plasma Concentrations of Lanadelumab by Immunogenicity Result | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 | The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the lanadelumab plasma concentrations was assessed. |
| Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 | The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the cHMWK levels was assessed. |
| Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | The number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a normalized monthly (4 weeks, i.e., 28 days). Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the investigator-confirmed HAE attacks during the efficacy evaluation period was assessed. |
| Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | The normalized number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of participants who achieved NNA \<1.0 per 4 weeks for the efficacy evaluation period were assessed. |
| Plasma Kallikrein (pKal) Activity | Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 | pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK). |
| Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. |
| Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | An HAE attack was confirmed by following symptoms/signs consistent with an attack in atleast one of the following locations:1)Peripheral angioedema:cutaneous swelling involving an extremity,the face,neck,torso,and/or genitourinary region;2)Abdominal angioedema:abdominal pain,with/without abdominal distention,nausea,vomiting,or diarrhea;3)Laryngeal angioedema:stridor,dyspnea, difficulty speaking,difficulty swallowing,throat tightening,or swelling of the tongue,palate,uvula,or larynx.Acute HAE attacks were managed per the investigator's usual care, including use of individualized acute therapy/rescue medications.Acute therapy/rescue medications included Firazyr, fresh frozen plasma (FFP), or other local standard of care.Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks requiring acute treatment occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. |
| Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182 | Day 0 through Day 182 | The severity of the investigator-confirmed HAE attacks was defined per the HAE attack assessment and reporting procedures (HAARP) definitions: severe (marked limitation in activity, assistance required), moderate (mild to moderate limitation in activity, some assistance needed). Treatment period attack rate per month is calculated as the number of moderate or severe investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in China from 22 June 2022 to 28 November 2023.
Pre-assignment details
A total of 20 participants with a diagnosis of hereditary angioedema (HAE) were enrolled in a Run-in Period of 4 to 8 weeks. Participants who experienced ≥1.0 investigator-confirmed HAE attack per 4 weeks during the Run-in Period and who remained eligible per inclusion and exclusion criteria entered the 26-week lanadelumab Treatment Period to receive lanadelumab 300 milligrams (mg).
Participants by arm
| Arm | Count |
|---|---|
| Lanadelumab 300 mg Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Lanadelumab 300 mg |
|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 11.6 |
| Body Mass Index (BMI) | 24.18 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 3.927 |
| Height | 166.83 centimeter (cm) STANDARD_DEVIATION 7.973 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 20 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 China | 20 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 7 Participants |
| Weight | 67.65 kilograms (kg) STANDARD_DEVIATION 13.551 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 14 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters
Laboratory parameters included clinical chemistry, hematology, coagulation, urinalysis, and serology. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters (including clinical chemistry, hematology, coagulation, urinalysis, and serology) were reported.
Time frame: From first dose of study drug up to end of study (up to Day 210)
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)
ECG included heart rate, PR interval, QRS duration, QT interval, corrected QT interval (QTc) interval, QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval, and QT corrected for heart rate by Bazett formula (QTcB) interval. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in ECG were reported.
Time frame: From first dose of study drug up to end of study (up to Day 210)
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG) | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities
Vital signs included measurement of blood pressure, heart rate, body temperature, and respiratory rate. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in vital signs were reported.
Time frame: From first dose of study drug up to end of study (up to Day 210)
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities | 0 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182
Physical examination findings by body system were classified as height and weight, general appearance, ears, nose and throat, head and neck, ophthalmological, respiratory, cardiovascular, abdomen, neurological, extremities, dermatological, and lymphatic. Number of participants with clinically significant changes in physical examination findings per investigator interpretation were reported. Only categories with at least one participant with event are reported.
Time frame: Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182 | Dermatologic System | 2 Participants |
| Lanadelumab 300 mg | Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182 | Extremities | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An SAE is any untoward clinical manifestation of signs, symptoms or outcomes whether considered related to investigational product or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category.
Time frame: From first dose of study drug up to end of study (up to Day 210)
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs: Angioedema Attack | 0 Participants |
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs: Non-Angioedema Attack | 15 Participants |
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs: Angioedema Attack | 3 Participants |
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs: Non-Angioedema Attack | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs: Angioedema Attack | 0 Participants |
| Lanadelumab 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs: Non-Angioedema Attack | 0 Participants |
Secondary
Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182
The number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a normalized monthly (4 weeks, i.e., 28 days). Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the investigator-confirmed HAE attacks during the efficacy evaluation period was assessed.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP). Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg | Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182 | At Least One Positive ADA Result | 0.00 attacks/month | — |
| Lanadelumab 300 mg | Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182 | No Positive ADA Result | 0.04 attacks/month | Standard Deviation 0.142 |
Secondary
Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182
An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182 | 0.04 attacks/month | Standard Deviation 0.139 |
Secondary
Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182
An HAE attack was confirmed by following symptoms/signs consistent with an attack in atleast one of the following locations:1)Peripheral angioedema:cutaneous swelling involving an extremity,the face,neck,torso,and/or genitourinary region;2)Abdominal angioedema:abdominal pain,with/without abdominal distention,nausea,vomiting,or diarrhea;3)Laryngeal angioedema:stridor,dyspnea, difficulty speaking,difficulty swallowing,throat tightening,or swelling of the tongue,palate,uvula,or larynx.Acute HAE attacks were managed per the investigator's usual care, including use of individualized acute therapy/rescue medications.Acute therapy/rescue medications included Firazyr, fresh frozen plasma (FFP), or other local standard of care.Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks requiring acute treatment occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182 | 0.01 attacks/month | Standard Deviation 0.034 |
Secondary
Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182
The severity of the investigator-confirmed HAE attacks was defined per the HAE attack assessment and reporting procedures (HAARP) definitions: severe (marked limitation in activity, assistance required), moderate (mild to moderate limitation in activity, some assistance needed). Treatment period attack rate per month is calculated as the number of moderate or severe investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182 | 0.01 attacks/month | Standard Deviation 0.034 |
Secondary
Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA
A run-in period of 4 weeks was included to determine the participant's baseline attack rate. This period may be extended up to 8 weeks. The normalized number of investigator-confirmed HAE attacks during efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate relative to the run-in period NNA. Number of participants who achieved at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed NNA per 4 weeks relative to the run-in period normalized NNA for the efficacy evaluation periods was assessed.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA | ≥50% Reduction | 20 Participants |
| Lanadelumab 300 mg | Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA | ≥70% Reduction | 20 Participants |
| Lanadelumab 300 mg | Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA | ≥90% Reduction | 19 Participants |
| Lanadelumab 300 mg | Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA | 100% Reduction | 18 Participants |
Secondary
Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182
An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. A participant was considered as attack free if the participant had no investigator-confirmed HAE attacks during the efficacy evaluation period. Number of participants who achieved attack-free status for the efficacy evaluation periods were assessed.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg | Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182 | 18 Participants |
Secondary
Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182
The normalized number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of participants who achieved NNA \<1.0 per 4 weeks for the efficacy evaluation period were assessed.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lanadelumab 300 mg | Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182 | 20 Participants |
Secondary
Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182
Number of participants with maximum HAE attack severity during the efficacy evaluation period was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 | No Attack | 18 Participants |
| Lanadelumab 300 mg | Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 | Mild | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 | Moderate | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182 | Severe | 0 Participants |
Secondary
Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma
Number of participants with neutralizing or non-neutralizing ADA in plasma were assessed.
Time frame: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP). Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 0 | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 56: Pre-dose | 0 Participants |
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 98: Pre-dose | 0 Participants |
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 140: Pre-dose | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 182: Pre-dose | 1 Participants |
| Lanadelumab 300 mg | Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Day 210 | 3 Participants |
Secondary
Plasma Concentrations of Lanadelumab
Time frame: Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182
Population: The Pharmacokinetic (PK) Set included all participants in the FAS who had at least 1 evaluable post-dose PK concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 0 | 7.64 nanograms per milliliter (ng/mL) | Standard Deviation 24.096 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 14: Pre-dose | 12336.47 nanograms per milliliter (ng/mL) | Standard Deviation 4531.386 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 56: Pre-dose | 24857.89 nanograms per milliliter (ng/mL) | Standard Deviation 6950.725 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 98: Pre-dose | 24170.00 nanograms per milliliter (ng/mL) | Standard Deviation 7260.426 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 140: Pre-dose | 23821.05 nanograms per milliliter (ng/mL) | Standard Deviation 8808.87 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 182: Pre-dose | 24610.00 nanograms per milliliter (ng/mL) | Standard Deviation 6599.673 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab | Day 210 | 12048.00 nanograms per milliliter (ng/mL) | Standard Deviation 3268.807 |
Secondary
Plasma Concentrations of Lanadelumab by Immunogenicity Result
The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the lanadelumab plasma concentrations was assessed.
Time frame: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182
Population: The PK set included all participants in the FAS who had at least 1 evaluable post-dose PK concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 56: Pre-dose: Negative ADA Result | 24857.89 ng/mL | Standard Deviation 6950.725 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 98: Pre-dose: Negative ADA Result | 24170.00 ng/mL | Standard Deviation 7260.426 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 0: Positive ADA Result | 0.00 ng/mL | — |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 0: Negative ADA Result | 8.04 ng/mL | Standard Deviation 24.687 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 140: Pre-dose: Positive ADA Result | 16700.00 ng/mL | — |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 140: Pre-dose: Negative ADA Result | 24216.67 ng/mL | Standard Deviation 8888.873 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 182: Pre-dose: Positive ADA Result | 27800.00 ng/mL | — |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 182: Pre-dose: Negative ADA Result | 24442.11 ng/mL | Standard Deviation 6736.494 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 210: Positive ADA Result | 13800.00 ng/mL | Standard Deviation 624.5 |
| Lanadelumab 300 mg | Plasma Concentrations of Lanadelumab by Immunogenicity Result | Day 210: Negative ADA Result | 11738.82 ng/mL | Standard Deviation 3458.715 |
Secondary
Plasma Kallikrein Activity cHMWK by Immunogenicity Result
The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the cHMWK levels was assessed.
Time frame: Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182
Population: The PD set included all participants in the FAS who had at least 1 evaluable post-dose PD concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 210: Negative ADA Result | 3599.373 ng/mL | Standard Deviation 1467.1561 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 0: Positive ADA Result | 13346.780 ng/mL | — |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 0: Negative ADA Result | 10093.768 ng/mL | Standard Deviation 3319.0248 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 56: Pre-dose: Negative ADA Result | 3604.136 ng/mL | Standard Deviation 1279.8551 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 98: Pre-dose: Negative ADA Result | 3312.706 ng/mL | Standard Deviation 1526.8282 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 140: Pre-dose: Positive ADA Result | 3733.890 ng/mL | — |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 140: Pre-dose: Negative ADA Result | 2823.446 ng/mL | Standard Deviation 1345.8483 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 182: Pre-dose: Positive ADA Result | 4577.960 ng/mL | — |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 182: Pre-dose: Negative ADA Result | 3320.814 ng/mL | Standard Deviation 1342.9683 |
| Lanadelumab 300 mg | Plasma Kallikrein Activity cHMWK by Immunogenicity Result | Day 210: Positive ADA Result | 4938.130 ng/mL | Standard Deviation 1367.0128 |
Secondary
Plasma Kallikrein (pKal) Activity
pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK).
Time frame: Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182
Population: The Pharmacodynamic (PD) Set included all participants in the FAS who had at least 1 evaluable post-dose PD concentration value. Number analyzed is the number of participants with data available for analyses at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 0 | 10256.419 ng/mL | Standard Deviation 3311.381 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 14: Pre-dose | 4904.964 ng/mL | Standard Deviation 1350.4121 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 56: Pre-dose | 3604.136 ng/mL | Standard Deviation 1279.8551 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 98: Pre-dose | 3312.706 ng/mL | Standard Deviation 1526.8282 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 140: Pre-dose | 2871.364 ng/mL | Standard Deviation 1324.5022 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 182: Pre-dose | 3383.672 ng/mL | Standard Deviation 1337.0341 |
| Lanadelumab 300 mg | Plasma Kallikrein (pKal) Activity | Day 210 | 3800.187 ng/mL | Standard Deviation 1499.9735 |
Secondary
Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182
Time to the first investigator-confirmed HAE attack (days) was calculated from the date and time of the first dose of study drug for that efficacy evaluation period to the date and time of the first investigator-confirmed HAE attack after the first dose for the efficacy evaluation period. The time to the first HAE attack was summarized using Kaplan-Meier (KM) estimates.
Time frame: Day 0 through Day 182
Population: The FAS included all participants who received at least 1 dose of lanadelumab (IP).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab 300 mg | Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182 | NA days |