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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lanadelumab 300 mg | Experimental | Participants received lanadelumab 300 milligrams (mg), subcutaneously (SC), once every 2 weeks (Q2W) from Day 0 to Day 182 (26 weeks). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanadelumab | Drug | Lanadelumab subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose of study drug up to end of study (up to Day 210) |
| 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. | From first dose of study drug up to end of study (up to Day 210) |
| 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. | From first dose of study drug up to end of study (up to Day 210) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentrations of Lanadelumab | Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 | |
| Plasma Kallikrein (pKal) Activity | pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK). |
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Inclusion Criteria:
Be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents.
The participant is male or female and greater than or equal to (>=) 12 years of age at the time of informed consent.
Documented diagnosis of HAE Type I or Type II based upon all of the following:
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.
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.
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.
Agree to adhere to the protocol-defined schedule of assessments and procedures.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Affiliated Hospital of Guangzhou Medical University | Guangzhou | Guangdong | 510260 | China | ||
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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 took part in the study at 4 investigative sites in China from 22 June 2022 to 28 November 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lanadelumab 300 mg | Participants received lanadelumab 300 mg, subcutaneously (SC), once every two weeks (Q2W) for 26 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Run-in Period (4 or up to 8 Weeks) |
| |||||||||||||
| Treatment Period (Weeks 1 to 26) |
| |||||||||||||
| Safety Follow-up Period (Weeks 27 to 30) |
|
The Full Analysis Set (FAS) included all participants who received at least 1 dose of lanadelumab (investigational product [IP]).
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| ID | Title | Description |
|---|---|---|
| BG000 | Lanadelumab 300 mg | Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | From first dose of study drug up to end of study (up to Day 210) |
From start of the study upto follow up (up to Day 210)
The FAS included all participants who received at least 1 dose of lanadelumab (IP). As per planned analysis, the adverse events were collected in a combined manner (to present under the treatment group of Lanadelumab 300 mg) only for the Treatment Period and Safety follow-up Period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lanadelumab 300 mg | Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 9, 2023 | May 23, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 10, 2023 | May 23, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
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| ID | Term |
|---|---|
| C000596550 | lanadelumab |
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| 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. | From first dose of study drug up to end of study (up to Day 210) |
| 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. | Day 182 |
| Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182 |
| 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. | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
| 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. | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
| 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. | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
| 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. | Day 0 through Day 182 |
| Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology |
| Wuhan |
| Hubei |
| 430030 |
| China |
| Yantai Yuhuangding Hospital | Yantai | Shandong | 264000 | China |
| Peking Union Medical College Hospital | Beijing | 100730 | China |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kilograms (kg) |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Body Mass Index (BMI) | BMI = weight (kg)/[height (m)^2] | Mean | Standard Deviation | kilograms per meter square (kg/m^2) |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Lanadelumab 300 mg | Participants received lanadelumab 300 mg, SC, Q2W for 26 weeks. |
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | From first dose of study drug up to end of study (up to Day 210) |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | From first dose of study drug up to end of study (up to Day 210) |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | From first dose of study drug up to end of study (up to Day 210) |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | Day 182 |
|
|
|
| Secondary | Plasma Concentrations of Lanadelumab | 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. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 |
|
|
|
| Secondary | Plasma Kallikrein (pKal) Activity | pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK). | 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. | Posted | Mean | Standard Deviation | ng/mL | Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Mean | Standard Deviation | attacks/month | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Mean | Standard Deviation | attacks/month | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Mean | Standard Deviation | attacks/month | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Median | Full Range | days | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
|
|
|
| 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. | The FAS included all participants who received at least 1 dose of lanadelumab (IP). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
|
|
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| 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. | 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. | Posted | Count of Participants | Participants | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | attacks/month | Day 0 through Day 182 |
|
|
|
| 0 |
| 20 |
| 1 |
| 20 |
| 14 |
| 20 |
| Spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA 26 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 26 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 26 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 26 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 26 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 26 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 26 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 26 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 26 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 26 | Systematic Assessment |
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The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |
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| Day 56: Pre-dose |
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| Day 98: Pre-dose |
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| Day 140: Pre-dose |
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| Day 182: Pre-dose |
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| Day 210 |
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| Day 56: Pre-dose |
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| Day 98: Pre-dose |
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| Day 140: Pre-dose |
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| Day 182: Pre-dose |
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| Day 210 |
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| Title | Measurements |
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| Severe |
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| Title | Measurements |
|---|---|
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| 100% Reduction |
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| Day 98: Pre-dose |
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| Day 140: Pre-dose |
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| Day 182: Pre-dose |
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| Day 210 |
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| Day 56: Pre-dose: Positive ADA Result |
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| Day 56: Pre-dose: Negative ADA Result |
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| Day 98: Pre-dose: Positive ADA Result |
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| Day 98: Pre-dose: Negative ADA Result |
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| Day 140: Pre-dose: Positive ADA Result |
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| Day 140: Pre-dose: Negative ADA Result |
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| Day 182: Pre-dose: Positive ADA Result |
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| Day 182: Pre-dose: Negative ADA Result |
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| Day 210: Positive ADA Result |
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| Day 210: Negative ADA Result |
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| Day 56: Pre-dose: Positive ADA Result |
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| Day 56: Pre-dose: Negative ADA Result |
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| Day 98: Pre-dose: Positive ADA Result |
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| Day 98: Pre-dose: Negative ADA Result |
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| Day 140: Pre-dose: Positive ADA Result |
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| Day 140: Pre-dose: Negative ADA Result |
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| Day 182: Pre-dose: Positive ADA Result |
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| Day 182: Pre-dose: Negative ADA Result |
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| Day 210: Positive ADA Result |
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| Day 210: Negative ADA Result |
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