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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04444895
Recruitment Status : Not yet recruiting
First Posted : June 24, 2020
Last Update Posted : October 12, 2020
Sponsor:
Collaborator:
Takeda Development Center Americas, Inc.
Information provided by (Responsible Party):
Takeda ( Shire )

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).

Condition or disease Intervention/treatment Phase
Angioedema Drug: Lanadelumab Phase 3

Detailed Description:
This study consists of 26-week treatment period (Day 0 to Day 182) and a 2-week follow-up period. Participants who completed the double-blind treatment period at Day 182 of Study SHP643-303 (NCT04206605) will enroll into this extension study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Lanadelumab
Rollover participants from SHP643-303 (NCT04206605) will receive 300 milligram (mg) of lanadelumab solution in prefilled syringe subcutaneously (SC) for 26 weeks once every 2 weeks (Q2W) or once every 4 weeks (Q4W) if well controlled during SHP643-303 (NCT04206605) with up to 13 doses.
Drug: Lanadelumab
Rollover participants will receive 300 mg of lanadelumab solution in a PFS SC injection once Q2W or Q4W for 26 consecutive weeks.
Other Names:
  • DX-2930
  • SHP643
  • TAK-743




Primary Outcome Measures :
  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From start of the study up to follow-up (Day 196) ]
    A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the investigational product or medicinal product. A SAE is any 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 will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.


Secondary Outcome Measures :
  1. 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 is 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 treatment period of Day 0 through Day 182 will be assessed.

  2. Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 [ Time Frame: Day 0 through Day 182 ]
    The overall severity of angioedema attack will be determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.

  3. Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 [ Time Frame: Day 0 through Day 182 ]
    A high morbidity angioedema attack is defined as any attack that has at least 1 of the following characteristics: severe, results in hospitalization (except hospitalization for observation less than (<) 24 hours), hemodynamically significant (systolic blood pressure less than < 90, requires intravenous (IV) hydration, or associated with syncope or near syncope) or laryngeal. Number of high-morbidity angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.

  4. Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab [ Time Frame: Day 0, 84, 140 and 182 ]
    Pharmacokinetic plasma concentrations of lanadelumab will be assessed.

  5. Plasma Kallikrein (pKal) Activity [ Time Frame: Day 0, 84, 140 and 182 ]
    Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) with factor XIIa activation level to assess pharmacodynamics of lanadelumab.

  6. Number of Participants With Positive Antidrug Antibodies (ADA) in Plasma [ Time Frame: Day 0, 84, 140 and 182 ]
    Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma will be assessed.

  7. Angioedema Quality of life (AE-QoL) Questionnaire [ Time Frame: Day 0, 28, 84, 140 and 182 ]
    The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema (including HAE). The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five-point response scale ranging from 1 (Never) to 5 (Very Often).

  8. Lanadelumab Injection Report During the Treatment Period of Day 0 Through Day 168 [ Time Frame: Day 0 through Day 168 ]
    An injection report will be completed by the participant (or parent/caregiver) following each dose administration of lanadelumab injection used during the treatment period of Day 0 through Day 168 will be assessed.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04444895


Contacts
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Contact: Takeda Development Center Americas Contact +1 866 842 5335 ClinicalTransparency@takeda.com

Locations
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United States, Alabama
Clinical Research Center of Alabama
Birmingham, Alabama, United States, 35209
Contact: Site Contact    205-209-4134    Janderson@alabamaallergy.com   
Principal Investigator: John Anderson         
United States, Arizona
Medical Research of Arizona a division of Allergy, Asthma & Immunology Associates, LTD
Scottsdale, Arizona, United States, 85251
Contact: Site Contact    480-675-8982    mm@medicalresearchaz.com   
Principal Investigator: Michael E Manning         
United States, California
UCSD Angioedema Center
San Diego, California, United States, 92122
Contact: Site Contact    858-657-5350    ask011@ucsd.edu   
Principal Investigator: Alexander Kim         
United States, Colorado
Asthma and Allergy Associates, PC
Colorado Springs, Colorado, United States, 80907
Contact: Site Contact    719-473-8330    dsoteres@aacos.com   
Principal Investigator: Daniel F Soteres         
United States, Maryland
Institute for Asthma & Allergy, P.C.
Chevy Chase, Maryland, United States, 20815
Contact: Site Contact    301-986-0670    hl@allergyasthma.us   
Principal Investigator: Huamin Henry Li         
United States, Michigan
University of Michigan Specialty Allergy Clinic and Food Allergy Clinic
Ann Arbor, Michigan, United States, 48106
Contact: Site Contact    734-936-5634    abaptist@med.umich.edu   
Principal Investigator: Alan Baptist         
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63414
Contact: Site Contact    314-996-8339    wednerj@wustl.edu   
Principal Investigator: H. James Wedner         
United States, Ohio
Optimed Research, LTD
Columbus, Ohio, United States, 43235
Contact: Site Contact    614-430-8022    pi@optimed.us.com   
Principal Investigator: Donald L McNeil         
Sponsors and Collaborators
Shire
Takeda Development Center Americas, Inc.
Investigators
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Study Director: Study Director Takeda Development Center Americas
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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT04444895    
Other Study ID Numbers: TAK-743-3001
2019-004823-20 ( EudraCT Number )
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn