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| ID | Type | Description | Link |
|---|---|---|---|
| 195014 | Registry Identifier | JapicCTI |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lanadelumab 300 mg q2w or q4w | Experimental | Lanadelumab 300 mg solution, subcutaneously (SC), once every 2 weeks (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 once every 4 weeks (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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanadelumab | Drug | Lanadelumab solution, SC |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 0 through Day 182 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toyohashi Municipal Hospital | Toyohashi | Aichi-ken | 441-8570 | Japan | ||
| Asahi General Hospital |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants).
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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.
A total of 12 participants took part in the study at 10 investigative sites in Japan from 12 December 2019 to 26 August 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lanadelumab 300 mg q2w or q4w | Lanadelumab 300 mg solution, subcutaneously (SC), once every 2 weeks (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 once every 4 weeks (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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Run-in Period (4 or up to 8 Weeks) |
| |||||||||||||
| Treatment Period A (Weeks 1 to 26) |
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| Treatment Period B (Weeks 27 to 52) |
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| Safety Follow-up Period (Weeks 53 to 56) |
|
Full Analysis Set (FAS) included all participants who received at least 1 dose of investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| 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 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | Day 0 through Day 182 |
|
From first dose of the study drug up to end of study (EOS) (up to Day 392)
FAS included all participants who received at least 1 dose of IMP. As Pre-specified in the protocol, the TEAEs 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.
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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 | Treatment Period A: Non-HAE | Lanadelumab 300 mg solution, SC, q2w for 26 weeks in Treatment Period A. Non-HAE attack (subset identified in CRF as not reported HAE attack) subset participants were included in this arm. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety disorder | Psychiatric disorders | MedDRA24.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1 866 842 5335 | ClinicalTransparency@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 | Oct 5, 2020 | Sep 19, 2022 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 23, 2021 | Sep 19, 2022 | SAP_003.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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| Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182 |
| 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. | Day 70 through Day 182 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364 |
| 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). | At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13 |
| 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. | Day 0 through Day 182 |
| 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. | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
| 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. | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
| 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 | 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. | Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392 |
| Plasma Kallikrein (pKal) Activity | pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics (PD) of lanadelumab. | Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 |
| 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). | Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 |
| 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. | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
| 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. | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
| 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. | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
| Asahi-shi |
| Chiba |
| 289-2511 |
| Japan |
| Ogaki Municipal Hospital | Ogaki-shi | Gifu | 503-8502 | Japan |
| Hiroshima University Hospital | Hiroshima | Hiroshima | 734-8551 | Japan |
| Tomakomai City Hospital | Tomakomai-shi | Hokkaido | 053-8567 | Japan |
| Kobe University Hospital | Kobe | Hyōgo | 650-0017 | Japan |
| Tokai University Hospital | Isehara-shi | Kanagawa | 259-1193 | Japan |
| Yokohama City University Hospital | Yokohama | Kanagawa | 236-0004 | Japan |
| Kyoto University Hospital | Kyoto | Kyoto | 606-8507 | Japan |
| Osaka University Hospital | Suita-shi | Osaka | 565-0871 | Japan |
| Saiyu Soka Hospital | Soka-shi | Saitama | 340-0041 | Japan |
| Shimane University Hospital | Izumo-shi | Shimane | 693-8501 | Japan |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
|
| Body Mass Index (BMI) | BMI= weight(kg) / height(meter)^2 | Mean | Standard Deviation | kg/m^2 |
|
| OG000 | 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. |
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Number | HAE attacks | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Number | HAE attacks | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Number | HAE attacks | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
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| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
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| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Number | HAE attacks | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Median | 95% Confidence Interval | days | Day 0 through Day 182 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Median | 95% Confidence Interval | days | Day 70 through Day 182 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | No | Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364 |
|
|
|
| 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). | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | Day 0 through Day 182 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Mean | Standard Deviation | percentage of attack-free days | Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
|
|
|
| Secondary | Plasma Concentrations of Lanadelumab | 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. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Mean | Standard Deviation | score on a scale | Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392 |
|
|
|
| Secondary | Plasma Kallikrein (pKal) Activity | pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics (PD) of lanadelumab. | 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. | Posted | Mean | Standard Deviation | percentage of cHMWK | Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 |
|
|
|
| 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). | 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. | Posted | Count of Participants | Participants | No | Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392 |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
|
|
|
| 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. | FAS included all participants who received at least 1 dose of IMP. | Posted | Count of Participants | Participants | No | From first dose of the study drug up to end of study (EOS) (up to Day 392) |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| 10 |
| 12 |
| EG001 | Treatment Period A: HAE | Lanadelumab 300 mg solution, SC, q2w for 26 weeks in Treatment Period A. HAE attack (subset of AEs identified in CRF as reported HAE attack) subset participants were included in this arm. | 0 | 12 | 1 | 12 | 7 | 12 |
| EG002 | Treatment Period B: Non-HAE | Lanadelumab 300 mg solution, SC, q2w for 26 weeks or lanadelumab 300 mg solution, SC, q4w for 26 weeks in Treatment Period B if well tolerated (attack-free) for 26 consecutive weeks with lanadelumab treatment during Treatment Period A. Non-HAE attack (subset identified in CRF as not reported HAE attack) subset participants were included in this arm. | 0 | 12 | 1 | 12 | 9 | 12 |
| EG003 | Treatment Period B: HAE | Lanadelumab 300 mg solution, SC, q2w for 26 weeks or lanadelumab 300 mg solution, SC, q4w for 26 weeks in Treatment Period B if well tolerated (attack-free) for 26 consecutive weeks with lanadelumab treatment during Treatment Period A. HAE attack (subset of AEs identified in CRF as reported HAE attack) subset participants were included in this arm. | 0 | 12 | 0 | 12 | 8 | 12 |
| EG004 | Safety Follow-up Period: Non-HAE | Participants who completed the lanadelumab 300 mg regimen in Treatment Period B returned on Day 378 (for participants who chose to roll over into study TAK-743-5007) or Day 392 as follow-up visit for final assessment in the Safety Follow-up Period. Non-HAE attack (subset identified in CRF as not reported HAE attack) subset participants were included in this arm. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG005 | Safety Follow-up Period: HAE | Participants who completed the lanadelumab 300 mg regimen in Treatment Period B returned on Day 378 (for participants who chose to roll over into study TAK-743-5007) or Day 392 as follow-up visit for final assessment in the Safety Follow-up Period. HAE attack (subset of AEs identified in CRF as reported HAE attack) subset participants were included in this arm. | 0 | 12 | 0 | 12 | 3 | 12 |
| Device related infection | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA24.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA24.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Hyperaesthesia teeth | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Large intestine polyp | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Infusion site pruritus | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA24.0 | Systematic Assessment |
|
| Allergy to chemicals | Immune system disorders | MedDRA24.0 | Systematic Assessment |
|
| Anaphylactic shock | Immune system disorders | MedDRA24.0 | Systematic Assessment |
|
| Contrast media allergy | Immune system disorders | MedDRA24.0 | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA24.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Laryngopharyngitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA24.0 | Systematic Assessment |
|
| Vulvitis | Infections and infestations | MedDRA24.0 | Systematic Assessment | Number of participants at risk in each arm is based on the female population in this study. |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Heat illness | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA24.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA24.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA24.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA24.0 | Systematic Assessment | Number of participants at risk in each arm is based on the female population in this study. |
|
| Headache | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
|
| Intercostal neuralgia | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
|
| Anxiety disorder | Psychiatric disorders | MedDRA24.0 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA24.0 | Systematic Assessment | Number of participants at risk in each arm is based on the female population in this study. |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA24.0 | Systematic Assessment |
|
| Alopecia areata | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Eczema asteatotic | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
|
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA24.0 | Systematic Assessment |
|
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 |
| Title | Measurements |
|---|---|
|
| Day 70 Through Day 364 |
|
| Title | Measurements |
|---|---|
|
| Day 70 Through Day 364 |
|
| Title | Measurements |
|---|---|
|
| Day 70 Through Day 364 |
|
| Title | Measurements |
|---|---|
|
| Day 0 Through Day 182: Severe |
|
| Day 0 Through Day 364: No Attack |
|
| Day 0 Through Day 364: Mild |
|
| Day 0 Through Day 364: Moderate |
|
| Day 0 Through Day 364: Severe |
|
| Day 70 Through Day 182: No Attack |
|
| Day 70 Through Day 182: Mild |
|
| Day 70 Through Day 182: Moderate |
|
| Day 70 Through Day 182: Severe |
|
| Day 70 Through Day 364: No Attack |
|
| Day 70 Through Day 364: Mild |
|
| Day 70 Through Day 364: Moderate |
|
| Day 70 Through Day 364: Severe |
|
| Title | Measurements |
|---|---|
|
| Day 70 Through Day 364 |
|
| Title | Measurements |
|---|---|
|
| Day 0 Through Day 364: ≥50% Reduction |
|
| Day 0 Through Day 364: ≥70% Reduction |
|
| Day 0 Through Day 364: ≥90% Reduction |
|
| Day 70 Through Day 182: ≥50% Reduction |
|
| Day 70 Through Day 182: ≥70% Reduction |
|
| Day 70 Through Day 182: ≥90% Reduction |
|
| Day 70 Through Day 364: ≥50% Reduction |
|
| Day 70 Through Day 364: ≥70% Reduction |
|
| Day 70 Through Day 364: ≥90% Reduction |
|
| Title | Measurements |
|---|---|
|
| Day 0 Through Day 182: <0.25 per Month |
|
| Day 0 Through Day 364: <1.0 per Month |
|
| Day 0 Through Day 364: <0.75 per Month |
|
| Day 0 Through Day 364: <0.50 per Month |
|
| Day 0 Through Day 364: <0.25 per Month |
|
| Day 70 Through Day 182: <1.0 per Month |
|
| Day 70 Through Day 182: <0.75 per Month |
|
| Day 70 Through Day 182: <0.50 per Month |
|
| Day 70 Through Day 182: <0.25 per Month |
|
| Day 70 Through Day 364: <1.0 per Month |
|
| Day 70 Through Day 364: <0.75 per Month |
|
| Day 70 Through Day 364: <0.50 per Month |
|
| Day 70 Through Day 364: <0.25 per Month |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|
|
| Month 4 |
|
| Month 5 |
|
| Month 6 |
|
| Month 7 |
|
| Month 8 |
|
| Month 9 |
|
| Month 10 |
|
| Month 11 |
|
| Month 12 |
|
| Month 13 |
|
| Title | Measurements |
|---|---|
|
| Day 70 Through Day 364 |
|
| AESI |
|
| Any Serious TEAEs |
|
|
| Day 98 |
|
|
| Day 140 |
|
|
| Day 182 |
|
|
| Day 266 |
|
|
| Day 350 |
|
|
| Day 364 |
|
|
| Day 378/392 |
|
|
| Title | Measurements |
|---|---|
|
| Day 98 |
|
| Day 126 |
|
| Day 154 |
|
| Day 182 |
|
| Day 266 |
|
| Day 364 |
|
| Day 378/392 |
|
|
| Day 98 |
|
|
| Day 140 |
|
|
| Day 182 |
|
|
| Day 266 |
|
|
| Day 350 |
|
|
| Day 364 |
|
|
| Day 378/392 |
|
|
|
| Day 98 |
|
|
| Day 140 |
|
|
| Day 182 |
|
|
| Day 266 |
|
|
| Day 350 |
|
|
| Day 364 |
|
|
| Day 378/392 |
|
|