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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001703-20 | EudraCT Number | ||
| jRCT2061210013 | Registry Identifier | Japan Ministry of Health, Labour and Welfare |
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| Name | Class |
|---|---|
| Takeda Development Center Americas, Inc. | INDUSTRY |
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The main aim of this study is to check if repeated subcutaneous (SC) injections of lanadelumab can prevent angioedema attacks in teenagers and adults with non-histaminergic angioedema with normal C1-INH. Another aim is to check if they tolerate the repeated SC injections.
Participants will receive a SC injection of lanadelumab every two weeks for 26 weeks. The first two doses of lanadelumab will be given at the study clinic. Once a participant (and/or parent/caregiver) has been appropriately trained, lanadelumab can be self-injected. Visits to the study clinic are planned for the first, third and fourth week and then every 4 weeks.
This study consists of non-histaminergic normal C1-INH angioedema population with 12 years of age and above. Participants will be randomized 2:1 to receive repeated SC administrations of lanadelumab or placebo in a double-blind fashion. Randomization will be stratified based on baseline angioedema attack rate (1 to less than (<) 2 attacks/4 weeks, and greater than (>=) 2 attacks/4 weeks), as well as subtype (known mutations, family history and unknown mutation, idiopathic).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 7 months. |
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| Lanadelumab 300mg | Experimental | Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once (q2w) for up to 6 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Other | Placebo-matching lanadelumab SC injection. |
| |
| Lanadelumab |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | An angioedema 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). 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 investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. | Day 0 through Day 182 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182 | An angioedema 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the treatment period of day 0 through day 182 was assessed. |
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Inclusion Criteria:
The Participant will not be considered eligible for the study without meeting all of the applicable population criteria below.
Males and females, 12 years of age and older for participants with non-histaminergic normal C1-INH angioedema at the time of signing of the informed consent form (ICF).
Documented clinical history of recurrent attacks of angioedema in the absence of wheals/urticaria.
Investigator-confirmed diagnosis of non-histaminergic bradykinin-mediated angioedema with normal C1-INH as documented by a history of angioedema attack(s) at screening and occurrence of attacks during the observation period:
Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
Participants >= 18 years of age must be willing to use icatibant as the rescue medication during the observation and treatment period. During the observation period, participants need to be treated with icatibant for at least 2 angioedema attacks or at least 1 moderate or severe attack. In the opinion of the investigator, participants with no response to icatibant for acute angioedema attacks in the past medical history/screening, or no improvement or worsened attack severity 2 hours after icatibant treatment during the observation period (based on totality of assessments), will not be included. Note: For participants 12 to < 18 years of age, standard of care therapy per local protocols should be provided.
Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study. Female participants of childbearing potential must have a negative serum pregnancy test at screening and must be willing to undergo pregnancy tests throughout the study. Females of non-childbearing potential are defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
The participants (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research ethics board/ethics committee (IRB/REB/EC).
If the participants 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 participants is a minor (i.e. < 18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (i.e. permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
Exclusion Criteria
The participant will be excluded from the study if any of the following exclusion criteria are met.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Center of Alabama | Birmingham | Alabama | 35209 | United States | ||
| Medical Research of Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40469312 | Derived | Riedl MA, Staubach P, Farkas H, Zanichelli A, Ren H, Nurse C, Andresen I, Juethner S, Yu M, Zhang J. Lanadelumab for prevention of attacks of non-histaminergic normal C1 inhibitor angioedema: results from the randomized, double-blind CASPIAN Study and CASPIAN open-label extension. Front Immunol. 2025 May 21;16:1502325. doi: 10.3389/fimmu.2025.1502325. eCollection 2025. |
| 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.
Participants with a diagnosis of non-histaminergic angioedema were randomized in a 2:1 ratio to receive lanadelumab or placebo.
Participants took part in the study at 34 investigative sites in Canada, United States, Germany, Hungary, Italy, Spain, France, Japan, Netherlands, and Poland from 04 May 2020 to 20 October 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 26 weeks. |
| FG001 | Lanadelumab 300 mg | Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 | Apr 19, 2021 | Oct 17, 2023 |
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| Drug |
Lanadelumab solution in a PFS for injection. |
|
|
| Day 0 through Day 182 |
| Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | Angioedema attack was defined as symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of tongue, palate, uvula, or larynx). Overall severity of the participant's angioedema attack was determined by site using the following definitions: 1. Mild: Transient or mild discomfort; 2. Moderate: Mild to moderate limitation in activity some assistance needed; 3. Severe: Marked limitation in activity, assistance required. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by number of days the participant contributed to the specified period multiplied by 28 days. | Day 0 Through Day 182 |
| Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the presumed steady state period of day 70 through day 182 were assessed. 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. | Day 70 through Day 182 |
| Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the presumed steady state period of day 70 through day 182 was assessed. | Day 70 through Day 182 |
| Number of Participants With Maximum Attack Severity During Treatment Period of Day 0 Through Day 182 | An angioedema 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 with maximum attack severity during treatment period of day 0 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. | Day 0 through Day 182 |
| Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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). 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 investigator-confirmed moderate or severe angioedema attacks during the presumed steady state period of day 70 through day 182 were assessed. | Day 70 through Day 182 |
| Number of Participants With Maximum Attack Severity During Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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 with maximum attack severity during the presumed steady state period of day 70 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. | Day 70 through Day 182 |
| Time to First Angioedema Attack After Day 0 Through Day 182 | The time to the first angioedema 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 angioedema attack after the first dose for the efficacy evaluation period of Day 0 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. | Day 0 Through Day 182 |
| Time to First Angioedema Attack After Day 70 Through Day 182 | The time to the first angioedema 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 angioedema attack after the first dose for the efficacy evaluation period of Day 70 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. | Day 70 through Day 182 |
| Number of Participants Achieving at Least 50 %, 70%, 90% and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks During Each of the Efficacy Evaluation Periods Relative to the Observation Period NNA | The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema 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 achieving at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks per 4 weeks during each of the efficacy evaluation periods relative to the observation period NNA was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. | Day 0 Through Day 182 |
| Number of Participants Achieving Normalized Number of Attacks (NNA) Less Than (<)1.0 Per 4 Weeks During Each of the Efficacy Evaluation Periods | The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema 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 achieving normalized number of attacks < 1.0 per 4 weeks during each of the efficacy evaluation periods was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. | Day 0 through Day 182, Day 70 through Day 182 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. SAE=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. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. | From the first study drug administration up to follow-up (Day 196) |
| Plasma Concentrations of Lanadelumab | Pre-dose and post-dose at Days 0, 4, 14, 28, 56, 84, 112, 140, 168 and 182 |
| Plasma Kallikrein (pKal) Activity | Plasma Kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK ) level to assess pharmacodynamics of lanadelumab. | Pre-dose and post-dose at Days 4, 14, 28, 56, 84, 112, 140, 168 and 182 |
| Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma | Number of participants with neutralizing or non-neutralizing antidrug antibodies in plasma was assessed. | Pre-dose and post-dose at Days 28, 56, 84, 112, 140, 168 and 182 |
| Number of Participants With Change in Total Angioedema Quality of Life (AE-QoL) Questionnaire Score During the Treatment Period of Day 0 Through Day 182 | The AE-QoL questionnaire was a self-administered validated instrument to assess health related (HR) QoL among participants with recurrent angioedema. The AE-QoL consisted of 17 disease-specific quality-of-life items, to produce a total AEQoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five point response scale ranging from 0 (Never) to 4 (Very Often). The raw total score (mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0 to 100. Swelling episodes (SE); Trouble Concentrating (TC); Food and Beverages (F&B); negative effects (NE). | Baseline through Day 182 |
| Scottsdale |
| Arizona |
| 85248 |
| United States |
| University of California San Diego | San Diego | California | 92122 | United States |
| AIRE Medical of Los Angeles | Santa Monica | California | 90404 | United States |
| Allergy and Asthma Clinical Research Inc | Walnut Creek | California | 94598 | United States |
| Asthma and Allergy Associates, PC | Colorado Springs | Colorado | 80907 | United States |
| University of South Florida Asthma, Allergy & Immunology | Tampa | Florida | 33613 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Kanarek Allergy, Asthma and Immunology | Overland Park | Kansas | 66211 | United States |
| Institute for Asthma & Allergy - Chevy Chase | Chevy Chase | Maryland | 20815 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02421 | United States |
| University of Michigan | Ann Arbor | Michigan | 48106 | United States |
| Mayo Clinic - Rochester | Rochester | Minnesota | 55905 | United States |
| Washington University | St Louis | Missouri | 63141 | United States |
| Jay M Kashkin, MD Allergy, Asthma and Immunology | Fair Lawn | New Jersey | 07410 | United States |
| Clinical Research of Charlotte | Charlotte | North Carolina | 28277 | United States |
| Bernstein Clinical Research Center, LLC | Cincinnati | Ohio | 45231 | United States |
| Optimed Research, LTD | Columbus | Ohio | 43235 | United States |
| Tanner Clinic | Layton | Utah | 84041 | United States |
| Seattle Allergy & Asthma Research Institute | Seattle | Washington | 98115 | United States |
| Ottawa Allergy Research Corporation | Ottawa | Ontario | K1G 6C6 | Canada |
| Clinique Specialisee en Allergie de la Capitale | Québec | Quebec | G1V 4W2 | Canada |
| CHU Grenoble Alpes, service de médecine interne, bureau de recherche clinique | Isere | 38043 | France |
| Service médecine interne, hôpital Saint Antoine | Paris | 75012 | France |
| Klinikum der Johann Wolfgang Goethe-Universitaet | Frankfurt am Main | Hesse | 60590 | Germany |
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Universitaetsklinikum Leipzig AoeR | Leipzig | Saxony | 4103 | Germany |
| Klinikum rechts der Isar der TUM, HNO Klinik und Poliklinik | Munich | 81675 | Germany |
| Semmelweis Egyetem | Budapest | 1088 | Hungary |
| Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco) | Milan | 20157 | Italy |
| DAI di Medicina Interna, Immunologia Clinica, Patologia Clinica, Malattie Infettive | Naples | 80131 | Italy |
| Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona | Salerno | 84131 | Italy |
| Hiroshima University Hospital | Hiroshima | 734-8851 | Japan |
| Kobe University Hospital | Hyōgo | 650-0017 | Japan |
| Amsterdam UMC | Amsterdam | 1105 AZ | Netherlands |
| Universitair Medisch Centrum Groningen | Groningen | 9713 GZ | Netherlands |
| UMC Utrecht | Utrecht | 3508 GA | Netherlands |
| NZOZ Homeo Medicus, Poradnia Alergologiczna | Bialystok | 15-867 | Poland |
| "ALL-MED" Specjalistyczna Opieka Medyczna Medyczny Instytut Badawczy | Wroclaw | 53-201 | Poland |
| Hospital Universitari de Bellvitge | L'Hospitalet de Llobregat | Barcelona | 8907 | Spain |
| Complexo Hospitalario Universitario de Vigo | Vigo | Pontevedra | 36312 | Spain |
| Hospital Universitario Cruces | Barakaldo | Vizcaya | 48903 | Spain |
| Hospital Universitari Vall d'Hebron | Barcelona | 8035 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Universitari i Politecnic La Fe | Valencia | 46026 | Spain |
| Steady State Full Analysis Set (SS-FAS) | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). |
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| COMPLETED |
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| NOT COMPLETED |
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Safety analysis set (SAS) included all participants who received any exposure to the investigational product.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 26 weeks. |
| BG001 | Lanadelumab 300 mg | Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | centimeter |
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| Weight | Mean | Standard Deviation | kilogram |
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| Body Mass Index (BMI) | BMI is calculated as [weight(kg)/height(m^2)]. | Mean | Standard Deviation | kilogram per squared meter |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | An angioedema 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). 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 investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. | Full Analysis Set (FAS) included all randomized participants who received any exposure to the investigational product (IP) during the treatment period (Day 0 through Day 182). | Posted | Mean | Standard Deviation | attacks/month | Day 0 through Day 182 |
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| Secondary | Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182 | An angioedema 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the treatment period of day 0 through day 182 was assessed. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
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| Secondary | Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | Angioedema attack was defined as symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of tongue, palate, uvula, or larynx). Overall severity of the participant's angioedema attack was determined by site using the following definitions: 1. Mild: Transient or mild discomfort; 2. Moderate: Mild to moderate limitation in activity some assistance needed; 3. Severe: Marked limitation in activity, assistance required. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by number of days the participant contributed to the specified period multiplied by 28 days. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). | Posted | Mean | Standard Deviation | attacks/month | Day 0 Through Day 182 |
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| Secondary | Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema attack was defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the presumed steady state period of day 70 through day 182 were assessed. 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. | Steady State (SS)-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). | Posted | Mean | Standard Deviation | attacks/month | Day 70 through Day 182 |
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| Secondary | Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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). A participant was considered as attack free during a time period if the participant has no investigator-confirmed angioedema attacks during that time period. For participants who discontinue the study prior to completion of the analysis period, participants were classified as attack-free or not based on the observed contribution to the analysis period. Number of participants achieving attack-free status during the presumed steady state period of day 70 through day 182 was assessed. | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). | Posted | Count of Participants | Participants | Day 70 through Day 182 |
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| Secondary | Number of Participants With Maximum Attack Severity During Treatment Period of Day 0 Through Day 182 | An angioedema 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 with maximum attack severity during treatment period of day 0 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). | Posted | Count of Participants | Participants | Day 0 through Day 182 |
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| Secondary | Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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). 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 investigator-confirmed moderate or severe angioedema attacks during the presumed steady state period of day 70 through day 182 were assessed. | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). | Posted | Mean | Standard Deviation | attacks/month | Day 70 through Day 182 |
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| Secondary | Number of Participants With Maximum Attack Severity During Presumed Steady State Period of Day 70 Through Day 182 | An angioedema 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 with maximum attack severity during the presumed steady state period of day 70 through day 182 was assessed. Angioedema attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe. | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). | Posted | Count of Participants | Participants | Day 70 through Day 182 |
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| Secondary | Time to First Angioedema Attack After Day 0 Through Day 182 | The time to the first angioedema 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 angioedema attack after the first dose for the efficacy evaluation period of Day 0 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). Number analyzed are the number of participants with attacks occurring as events. | Posted | Median | 95% Confidence Interval | days | Day 0 Through Day 182 |
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| Secondary | Time to First Angioedema Attack After Day 70 Through Day 182 | The time to the first angioedema 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 angioedema attack after the first dose for the efficacy evaluation period of Day 70 through Day 182. Participants with attacks occurring were the events. Participants who discontinue/complete the study prior to having an angioedema attack were censored. The data is reported for baseline angioedema attack rate groups i.e. 1 to < 2 Attacks/Month and >=2 Attacks/Month. | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). Number analyzed are the number of participants with attacks occurring as events. | Posted | Median | 95% Confidence Interval | days | Day 70 through Day 182 |
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| Secondary | Number of Participants Achieving at Least 50 %, 70%, 90% and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks During Each of the Efficacy Evaluation Periods Relative to the Observation Period NNA | The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema 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 achieving at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks per 4 weeks during each of the efficacy evaluation periods relative to the observation period NNA was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). Overall number of participants analyzed are the number of participants achieving at Least 50 %, 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks. | Posted | Count of Participants | Participants | Day 0 Through Day 182 |
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| Secondary | Number of Participants Achieving Normalized Number of Attacks (NNA) Less Than (<)1.0 Per 4 Weeks During Each of the Efficacy Evaluation Periods | The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period was expressed as a monthly (28 days) angioedema 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 achieving normalized number of attacks < 1.0 per 4 weeks during each of the efficacy evaluation periods was assessed. The percentage reduction groups are not mutually exclusive, participants may appear in more than one group as applicable based on their percentage reduction. | SS-FAS included all randomized participants who received any exposure to the investigational product during the presumed steady state period (Day 70 through Day 182). | Posted | Count of Participants | Participants | Day 0 through Day 182, Day 70 through Day 182 |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) | TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. SAE=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. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. | SAS included all participants who received any exposure to the IP. | Posted | Count of Participants | Participants | From the first study drug administration up to follow-up (Day 196) |
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| Secondary | Plasma Concentrations of Lanadelumab | Pharmacokinetic Set (PK Set) included all participants in the SAS who had at least 1 evaluable postdose PK concentration value. Overall number of participants analyzed is the number of participants available with data for analyses. Number analyzed is the number of participants available for analyses at the given timepoint. | Posted | Mean | Standard Deviation | nanogram/milliliter (ng/mL) | Pre-dose and post-dose at Days 0, 4, 14, 28, 56, 84, 112, 140, 168 and 182 |
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| Secondary | Plasma Kallikrein (pKal) Activity | Plasma Kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK ) level to assess pharmacodynamics of lanadelumab. | The Pharmacodynamic Set (PD Set) included all participants in the SAS who had at least 1 evaluable PD concentration value. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants available for analyses at the given timepoint. | Posted | Mean | Standard Deviation | % cHMWK | Pre-dose and post-dose at Days 4, 14, 28, 56, 84, 112, 140, 168 and 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 antidrug antibodies in plasma was assessed. | FAS included all randomized participants who receive any exposure to the IP during the treatment period (Day 0 through Day 182). Number analyzed is the number of participants available for analyses at the given timepoint. | Posted | Count of Participants | Participants | Pre-dose and post-dose at Days 28, 56, 84, 112, 140, 168 and 182 |
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| Secondary | Number of Participants With Change in Total Angioedema Quality of Life (AE-QoL) Questionnaire Score During the Treatment Period of Day 0 Through Day 182 | The AE-QoL questionnaire was a self-administered validated instrument to assess health related (HR) QoL among participants with recurrent angioedema. The AE-QoL consisted of 17 disease-specific quality-of-life items, to produce a total AEQoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five point response scale ranging from 0 (Never) to 4 (Very Often). The raw total score (mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0 to 100. Swelling episodes (SE); Trouble Concentrating (TC); Food and Beverages (F&B); negative effects (NE). | SAS included all participants who receive any exposure to the IP. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants available for analyses in the specific category. | Posted | Count of Participants | Participants | Baseline through Day 182 |
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From start of the study up to follow up (Day 196)
Not provided
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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 | Placebo | Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 26 weeks. | 0 | 27 | 1 | 27 | 27 | 27 |
| EG001 | Lanadelumab 300 mg | Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks. | 0 | 50 | 7 | 50 | 49 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis staphylococcal | Infections and infestations | 25.0 | Systematic Assessment |
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| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Lymphoedema | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.0 | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 10, 2022 | Oct 17, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000799 | Angioedema |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000596550 | lanadelumab |
Not provided
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| France |
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| Germany |
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| Hungary |
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| Italy |
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| Japan |
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| Netherlands |
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| Poland |
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| Spain |
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| United States |
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Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks.
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Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks.
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Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks. |
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| Lanadelumab 300 mg |
Participants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once q2w for up to 26 weeks. |
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