AngioedemaPhase 3NCT04206605
A Study of Lanadelumab in Teenagers and Adults to Prevent Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
A Phase 3 study testing Lanadelumab in people with Angioedema, run by Takeda at 45 sites in 10 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Angioedema
- What is being tested?
- Lanadelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 45 sitesin 10 countries
- Study dates
- 4 May 2020to 20 Oct 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- History of recurrent angioedema with at least an average of 1 angioedema attack per 4 weeks prior to screening and this attack rate must be confirmed during the observation period while treated with chronic high-dose antihistamine (cetirizine 40 milligram per day [mg/day] or equivalent high-dose second-generation antihistamine medication).
- Diagnostic testing results obtained during screening from a sponsor-approved central laboratory that confirm C1-INH function >= 50 percent (%) of normal and C4 level not below the normal range. With prior sponsor approval, participants may be retested during the observation period if results are incongruent with clinical history.
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- Clinical history of not responding to high-dose antihistamine treatment (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication), which must be confirmed during the observation period with at least 1 angioedema attack per 4 weeks with chronic high-dose antihistamine treatment and no significant difference (as assessed by the investigator and in consultation with the sponsor's medical monitor, as necessary) from the historic attack rate without high-dose antihistamine treatment.
- 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.
Who cannot join
- The participant will be excluded from the study if any of the following exclusion criteria are met.
- Concomitant diagnosis of Type I or Type II HAE, or recurrent angioedema associated with urticaria.
- Dosing with any investigational drug or exposure to an investigational device within 4 weeks prior to screening.
- Exposure to angiotensin-converting enzyme (ACE) inhibitors or rituximab within 6 months prior to screening.
- Use of any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
- Response to omalizumab (prophylactic) or corticosteroid (acute/prophylactic) or epinephrine (acute) or anti-leukotrienes (prophylactic) treatments in the past.
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- Use of long-term prophylactic therapy for HAE, e.g. C1-INH, attenuated androgens (e.g. danazol, methyltestosterone, testosterone), or anti-fibrinolytics within 2 weeks prior to entering the observation period as long as the investigator determines that doing so would not place the participant at any undue safety risk, and that the participant is at least 18 years of age.
- Any exposure to prophylactic plasma kallikrein inhibitors prior to screening.
- Use of short-term prophylaxis for HAE within 7 days prior to entering the observation period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or anti-fibrinolytics used to avoid angioedema complications from medically indicated procedures.
- Have any active infectious illness or fever defined as an oral temperature greater than (>) 38°C (100.4°F), tympanic > 38.5°C (101.3°F), axillary > 38°C (100.4°F), or rectal/core > 38.5°C (101.3°F) within 24 hours prior to the first dose of study drug in the treatment period.
- Any of the following liver function test abnormalities: alanine aminotransferase (ALT) > 3x upper limit of normal, or aspartate aminotransferase (AST) > 3x upper limit of normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's syndrome).
- Pregnancy or breast feeding.
- Participant has a known hypersensitivity to the investigational product or its components.
- Have any uncontrolled underlying medical condition which would require treatment adjustment during the study treatment period that, in the opinion of the investigator or sponsor, may confound the results of the safety assessments or may place the participant at risk. Participants with stable treatment for at least 3 months prior to screening and NOT expecting any change to their treatment regimen for 6 months during the study treatment period, will not be excluded.
- Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).
Trial locations and contacts
45 sites in 10 countries.
45 sites in 10 countries
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48106
Clinical Research Center of Alabama
Birmingham, Alabama, 35209
Massachusetts General Hospital
Boston, Massachusetts, 02421
Clinical Research of Charlotte
Charlotte, North Carolina, 28277
Institute for Asthma & Allergy - Chevy Chase
Chevy Chase, Maryland, 20815
Rush University Medical Center
Chicago, Illinois, 60612
Bernstein Clinical Research Center, LLC
Cincinnati, Ohio, 45231
Asthma and Allergy Associates, PC
Colorado Springs, Colorado, 80907
Optimed Research, LTD
Columbus, Ohio, 43235
Jay M Kashkin, MD Allergy, Asthma and Immunology
Fair Lawn, New Jersey, 07410
Tanner Clinic
Layton, Utah, 84041
Kanarek Allergy, Asthma and Immunology
Overland Park, Kansas, 66211
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
University of California San Diego
San Diego, California, 92122
AIRE Medical of Los Angeles
Santa Monica, California, 90404
Medical Research of Arizona
Scottsdale, Arizona, 85248
Seattle Allergy & Asthma Research Institute
Seattle, Washington, 98115
Washington University
St Louis, Missouri, 63141
University of South Florida Asthma, Allergy & Immunology
Tampa, Florida, 33613
Allergy and Asthma Clinical Research Inc
Walnut Creek, California, 94598
Spain6 sites
Hospital Universitario Cruces
Barakaldo, Vizcaya, 48903
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 8907
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Complexo Hospitalario Universitario de Vigo
Vigo, Pontevedra, 36312
Germany4 sites
Klinikum der Johann Wolfgang Goethe-Universitaet
Frankfurt am Main, Hesse, 60590
Universitaetsklinikum Leipzig AoeR
Leipzig, Saxony, 4103
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, Rhineland-Palatinate, 55131
Klinikum rechts der Isar der TUM, HNO Klinik und Poliklinik
Munich, 81675
Italy3 sites
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
Milan, 20157
DAI di Medicina Interna, Immunologia Clinica, Patologia Clinica, Malattie Infettive
Naples, 80131
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno, 84131
Netherlands3 sites
Amsterdam UMC
Amsterdam, 1105 AZ
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
UMC Utrecht
Utrecht, 3508 GA
Canada2 sites
Ottawa Allergy Research Corporation
Ottawa, Ontario, K1G 6C6
Clinique Specialisee en Allergie de la Capitale
Québec, Quebec, G1V 4W2
France2 sites
CHU Grenoble Alpes, service de médecine interne, bureau de recherche clinique
Isere, 38043
Service médecine interne, hôpital Saint Antoine
Paris, 75012
Japan2 sites
Hiroshima University Hospital
Hiroshima, 734-8851
Kobe University Hospital
Hyōgo, 650-0017
Poland2 sites
NZOZ Homeo Medicus, Poradnia Alergologiczna
Bialystok, 15-867
"ALL-MED" Specjalistyczna Opieka Medyczna Medyczny Instytut Badawczy
Wroclaw, 53-201
About this study
Official title: A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
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.
Read the detailed description
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).
- Conditions
- Angioedema
- Being tested
- Placebo, Lanadelumab
- Keywords
- Drug Therapy
- Medical subject headings
- Angioedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Placebo-matching lanadelumab SC injection.
LanadelumabDrug
Also called SHP643, DX-2930, TAK-743
Lanadelumab solution in a PFS for injection.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 7 months. Receives: Other: Placebo |
| 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. Receives: Drug: Lanadelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0 through Day 182
Secondary outcomes (16)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the first study drug administration up to follow-up (Day 196)
Plasma Concentrations of Lanadelumab
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Baseline through Day 182
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start4 May 2020
- Primary completion20 Oct 2022
- Study completion20 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AngioedemaStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206605
- Sponsor's protocol ID
- SHP643-303
- Other IDs
- 2019-001703-20, jRCT2061210013, 2019
- Status last verified
- Dec 2023
- First submitted
- 18 Dec 2019
- Last updated
- 27 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40469312
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
- ClinicalTrials.gov ID
- NCT04206605
- Acronym / sponsor ID
- SHP643-303
- Conditions
- Angioedema
- Keywords
- Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 4 May 2020 (actual)
- Primary completion
- 20 Oct 2022 (actual)
- Study completion
- 20 Oct 2022 (actual)
- First posted
- 20 Dec 2019 (actual)
- Results
- Posted 27 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboParticipants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 7 months. |
| Lanadelumab 300mg | Experimental | Drug: LanadelumabParticipants received 300 mg of lanadelumab solution in a prefilled syringe (PFS) as SC injection once (q2w) for up to 6 months. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (15 listed)
- The participant will be excluded from the study if any of the following exclusion criteria are met.
- Concomitant diagnosis of Type I or Type II HAE, or recurrent angioedema associated with urticaria.
- Dosing with any investigational drug or exposure to an investigational device within 4 weeks prior to screening.
- Exposure to angiotensin-converting enzyme (ACE) inhibitors or rituximab within 6 months prior to screening.
- Use of any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo-matching lanadelumab SC injection. | Other | Placebo |
| LanadelumabAlso: SHP643, DX-2930, TAK-743Lanadelumab solution in a PFS for injection. | Drug | Lanadelumab 300mg |
Primary outcome
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
Time frame: 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.
16 secondary outcomes
Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182
Time frame: Day 0 through Day 182
Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
Time frame: Day 0 Through Day 182
Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182
Time frame: Day 70 through Day 182
Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182
Time frame: Day 70 through Day 182
Number of Participants With Maximum Attack Severity During Treatment Period of Day 0 Through Day 182
Time frame: 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
Time frame: Day 70 through Day 182
Number of Participants With Maximum Attack Severity During Presumed Steady State Period of Day 70 Through Day 182
Time frame: Day 70 through Day 182
Time to First Angioedema Attack After Day 0 Through Day 182
Time frame: Day 0 Through Day 182
Time to First Angioedema Attack After Day 70 Through Day 182
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: From the first study drug administration up to follow-up (Day 196)
Plasma Concentrations of Lanadelumab
Time frame: Pre-dose and post-dose at Days 0, 4, 14, 28, 56, 84, 112, 140, 168 and 182
Plasma Kallikrein (pKal) Activity
Time frame: 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
Time frame: 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
Time frame: Baseline through Day 182
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40469312Riedl 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.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
45 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lanadelumab in people with Angioedema, run by Takeda at 45 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Spain, Germany, Italy, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 (time frame: Day 0 through Day 182). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04206605, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2023.