A Study of Lanadelumab in Teenagers and Adults to Prevent Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)

NCT04206605 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: SHP643-3032019-001703-20jRCT2061210013
• Study Type: interventional
• Target: 77
• Locations: 10 countries
• Sites: 45

Brief 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. 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.

Conditions

Angioedema

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (16)

• Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182

  Day 0 through Day 182

• Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

  Day 0 Through Day 182

• Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182

  Day 70 through Day 182

• Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182

  Day 70 through Day 182

• Number of Participants With Maximum Attack Severity During Treatment Period of Day 0 Through Day 182

  Day 0 through Day 182

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants received placebo-matching lanadelumab subcutaneous (SC) injection once every 2 weeks (q2w) for up to 7 months.

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.

Drug: Lanadelumab

Interventions

Placebo OTHER

Placebo-matching lanadelumab SC injection.

Placebo

Lanadelumab DRUG

Lanadelumab solution in a PFS for injection.

Also known as: SHP643, DX-2930, TAK-743

Lanadelumab 300mg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• \- 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (45)

Clinical Research Center of Alabama

Birmingham, Alabama, 35209, United States

Location

Medical Research of Arizona

Scottsdale, Arizona, 85248, United States

Location

University of California San Diego

San Diego, California, 92122, United States

Location

AIRE Medical of Los Angeles

Santa Monica, California, 90404, United States

Location

Allergy and Asthma Clinical Research Inc

Walnut Creek, California, 94598, United States

Location

Asthma and Allergy Associates, PC

Colorado Springs, Colorado, 80907, United States

Location

University of South Florida Asthma, Allergy & Immunology

Tampa, Florida, 33613, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kanarek Allergy, Asthma and Immunology

Overland Park, Kansas, 66211, United States

Location

Institute for Asthma & Allergy - Chevy Chase

Chevy Chase, Maryland, 20815, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02421, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63141, United States

Location

Jay M Kashkin, MD Allergy, Asthma and Immunology

Fair Lawn, New Jersey, 07410, United States

Location

Clinical Research of Charlotte

Charlotte, North Carolina, 28277, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45231, United States

Location

Optimed Research, LTD

Columbus, Ohio, 43235, United States

Location

Tanner Clinic

Layton, Utah, 84041, United States

Location

Seattle Allergy & Asthma Research Institute

Seattle, Washington, 98115, United States

Location

Ottawa Allergy Research Corporation

Ottawa, Ontario, K1G 6C6, Canada

Location

Clinique Specialisee en Allergie de la Capitale

Québec, Quebec, G1V 4W2, Canada

Location

CHU Grenoble Alpes, service de médecine interne, bureau de recherche clinique

Isere, 38043, France

Location

Service médecine interne, hôpital Saint Antoine

Paris, 75012, France

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, 4103, Germany

Location

Klinikum rechts der Isar der TUM, HNO Klinik und Poliklinik

Munich, 81675, Germany

Location

Semmelweis Egyetem

Budapest, 1088, Hungary

Location

Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, 20157, Italy

Location

DAI di Medicina Interna, Immunologia Clinica, Patologia Clinica, Malattie Infettive

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, 84131, Italy

Location

Hiroshima University Hospital

Hiroshima, 734-8851, Japan

Location

Kobe University Hospital

Hyōgo, 650-0017, Japan

Location

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

NZOZ Homeo Medicus, Poradnia Alergologiczna

Bialystok, 15-867, Poland

Location

"ALL-MED" Specjalistyczna Opieka Medyczna Medyczny Instytut Badawczy

Wroclaw, 53-201, Poland

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 8907, Spain

Location

Complexo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36312, Spain

Location

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Publications (1)

• 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.

  PMID: 40469312 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Angioedema

Interventions

lanadelumab

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 20, 2019
• Study Start: May 4, 2020
• Primary Completion: October 20, 2022
• Study Completion: October 20, 2022
• Last Updated: December 27, 2023
• Results First Posted: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: 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.

Locations

DE (4); JP (2); IT (3); CA (2); US (20); FR (2); NL (3); ES (6); HU (1); PL (2)