A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor

NCT04444895 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: TAK-743-30012019-004823-20jRCT2051220001
• Study Type: interventional
• Target: 73
• Locations: 10 countries
• Sites: 35

Brief Summary

The purpose of this study is to evaluate the long-term safety and efficacy of repeated subcutaneous (SC) administration of lanadelumab in adolescents and adults with non-histaminergic angioedema with normal C1-inhibitor who completed study SHP643-303 (NCT04206605).

Conditions

Angioedema

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period

  TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP 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. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

  From Day 0 up to Day 182

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up

  TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP 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. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.

  From Day 183 up to Day 196

Secondary Outcomes (12)

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

  From Day 0 up to Day 182

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

  From Day 0 up to Day 182

• Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

  From Day 0 up to Day 182

• Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

  Predose on Days 0, 84, and 140 and postdose on Day 182

• Plasma Kallikrein (pKal) Activity

  Predose on Days 0, 84, and 140 and postdose on Day 182

Study Arms (1)

Lanadelumab 300 mg Every 2 Weeks

EXPERIMENTAL

Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.

Drug: Lanadelumab

Interventions

Lanadelumab DRUG

Lanadelumab SC injection

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

Lanadelumab 300 mg Every 2 Weeks

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:

• Males and females, 12 years of age and older diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303 (NCT04206605).
• Participants must have completed the treatment period (through Visit 26/Day 182) of Study SHP643-303 (NCT04206605) without reporting a clinically significant TEAE that would preclude subsequent exposure to lanadelumab.
• Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
• 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; or females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
• The participant (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) at any time prior to study start. If the participant is a minor (i.e. lesser then (\<) 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:

• Discontinued from Study SHP643-303 (NCT04206605) after enrollment but before Visit 26 for any reason.
• Presence of important safety concerns identified in Study SHP643-303 (NCT04206605) that would preclude participation in this study.
• Dosing with an investigational product (IP, not including IP defined in antecedent Study SHP643-303 \[NCT04206605\]) or exposure to an investigational device within 4 weeks prior to Day 0.
• Participants has a known hypersensitivity to the investigational product or its components.
• 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

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

Study Sites (35)

Clinical Research Center of Alabama

Birmingham, Alabama, 35209, United States

Location

Medical Research of Arizona

Scottsdale, Arizona, 85248, United States

Location

UCSD Angioedema Center

San Diego, California, 92122, 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

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, P.C.

Chevy Chase, Maryland, 20815, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63141, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45236, United States

Location

Optimed Research, LTD

Columbus, Ohio, 43235, United States

Location

Seattle Allergy & Asthma Research Institute

Seattle, Washington, 98115, United States

Location

Ottawa Allergy Research Corporation

Ottawa, Ontario, K1H 1E4, Canada

Location

Clinique Specialisee en Allergie de la Capitale

Québec, Quebec, G1V 4W2, Canada

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Klinikum rechts der Isar der TU

Munich, Bavaria, 81675, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet pt

Frankfurt am Main, Hesse, 60590, Germany

Location

Semmelweis Egyetem

Budapest, 1088, Hungary

Location

A.O. Ospedali riuniti Villa Sofia - Cervello,

Palermo, Palermo Palermo, 90100, Italy

Location

Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, 20157, Italy

Location

Azienda Ospedaliera Universitaria "Federico II"

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, Hiroshima, 734-8551, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Clover Hospital

Fujisawa-shi, Kanagawa, 251-0025, 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 Filia

Wroclaw, 53-201, Poland

Location

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, 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 Development Center Americas

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 24, 2020
• Study Start: February 5, 2021
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2023
• Last Updated: June 17, 2024
• Results First Posted: June 17, 2024

Record last verified: 2024-06

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

US (15); DE (2); FR (1); NL (3); HU (1); CA (2); PL (2); JP (3); ES (2); IT (4)