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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

Primary Purpose

Angioedema

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lanadelumab
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angioedema

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Clinical Research Center of Alabama
  • Medical Research of Arizona
  • UCSD Angioedema Center
  • Allergy and Asthma Clinical Research Inc
  • Asthma and Allergy Associates, PC
  • Rush University Medical Center
  • Kanarek Allergy, Asthma and Immunology
  • Institute for Asthma & Allergy, P.C.
  • Massachusetts General Hospital
  • University of Michigan
  • Mayo Clinic
  • Washington University
  • Bernstein Clinical Research Center, LLC
  • Optimed Research, LTD
  • Seattle Allergy & Asthma Research Institute
  • Ottawa Allergy Research Corporation
  • Clinique Specialisee en Allergie de la Capitale
  • Hôpital Saint-Antoine
  • Klinikum rechts der Isar der TU
  • Klinikum der Johann Wolfgang Goethe-Universitaet pt
  • Semmelweis Egyetem
  • A.O. Ospedali riuniti Villa Sofia - Cervello,
  • Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
  • Azienda Ospedaliera Universitaria "Federico II"
  • Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
  • Hiroshima University Hospital
  • Kobe University Hospital
  • Clover Hospital
  • Amsterdam UMC
  • Universitair Medisch Centrum Groningen
  • UMC Utrecht
  • NZOZ Homeo Medicus, Poradnia Alergologiczna
  • "ALL-MED" Specjalistyczna Opieka Medyczna Filia
  • Hospital Universitario Cruces
  • Hospital Universitari Vall d'Hebron

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lanadelumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants with Treatment Emergent Adverse Events (TEAEs)
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

Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of 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.
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of 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.
Number of High-Morbidity Angioedema Attacks During the Treatment Period of 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.
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
Pharmacokinetic plasma concentrations of lanadelumab will be assessed.
Plasma Kallikrein (pKal) Activity
Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) with factor XIIa activation level to assess pharmacodynamics of lanadelumab.
Number of Participants With Positive Antidrug Antibodies (ADA) in Plasma
Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma will be assessed.
Angioedema Quality of life (AE-QoL) Questionnaire
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).
Lanadelumab Injection Report During the Treatment Period of 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.

Full Information

First Posted
June 16, 2020
Last Updated
June 15, 2023
Sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04444895
Brief Title
A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 5, 2021 (Actual)
Primary Completion Date
May 5, 2023 (Actual)
Study Completion Date
May 5, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angioedema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lanadelumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lanadelumab
Other Intervention Name(s)
DX-2930, SHP643, TAK-743
Intervention Description
Rollover participants will receive 300 mg of lanadelumab solution in a PFS SC injection once Q2W or Q4W for 26 consecutive weeks.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From start of the study up to follow-up (Day 196)
Secondary Outcome Measure Information:
Title
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
Description
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.
Time Frame
Day 0 through Day 182
Title
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
Description
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.
Time Frame
Day 0 through Day 182
Title
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
Description
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.
Time Frame
Day 0 through Day 182
Title
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
Description
Pharmacokinetic plasma concentrations of lanadelumab will be assessed.
Time Frame
Day 0, 84, 140 and 182
Title
Plasma Kallikrein (pKal) Activity
Description
Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) with factor XIIa activation level to assess pharmacodynamics of lanadelumab.
Time Frame
Day 0, 84, 140 and 182
Title
Number of Participants With Positive Antidrug Antibodies (ADA) in Plasma
Description
Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma will be assessed.
Time Frame
Day 0, 84, 140 and 182
Title
Angioedema Quality of life (AE-QoL) Questionnaire
Description
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).
Time Frame
Day 0, 28, 84, 140 and 182
Title
Lanadelumab Injection Report During the Treatment Period of Day 0 Through Day 168
Description
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.
Time Frame
Day 0 through Day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda Development Center Americas
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Medical Research of Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85248
Country
United States
Facility Name
UCSD Angioedema Center
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
Allergy and Asthma Clinical Research Inc
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Asthma and Allergy Associates, PC
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Kanarek Allergy, Asthma and Immunology
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
Institute for Asthma & Allergy, P.C.
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Bernstein Clinical Research Center, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
Optimed Research, LTD
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Seattle Allergy & Asthma Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98115
Country
United States
Facility Name
Ottawa Allergy Research Corporation
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 1E4
Country
Canada
Facility Name
Clinique Specialisee en Allergie de la Capitale
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
Hôpital Saint-Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Klinikum rechts der Isar der TU
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Klinikum der Johann Wolfgang Goethe-Universitaet pt
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
A.O. Ospedali riuniti Villa Sofia - Cervello,
City
Palermo
State/Province
Palermo Palermo
ZIP/Postal Code
90100
Country
Italy
Facility Name
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
City
Milano
ZIP/Postal Code
20157
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria "Federico II"
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
City
Salerno
ZIP/Postal Code
84131
Country
Italy
Facility Name
Hiroshima University Hospital
City
Hiroshima-shi
State/Province
Hiroshima-Ken
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe-shi
State/Province
Hyogo-Ken
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Clover Hospital
City
Fujisawa-shi
State/Province
Kanagawa-Ken
ZIP/Postal Code
251-0025
Country
Japan
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
UMC Utrecht
City
Utrecht
ZIP/Postal Code
3508 GA
Country
Netherlands
Facility Name
NZOZ Homeo Medicus, Poradnia Alergologiczna
City
Bialystok
ZIP/Postal Code
15-867
Country
Poland
Facility Name
"ALL-MED" Specjalistyczna Opieka Medyczna Filia
City
Wroclaw
ZIP/Postal Code
53-201
Country
Poland
Facility Name
Hospital Universitario Cruces
City
Barakaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b600d4db2bf003ab48cf1?idFilter=%5B%22TAK-743-3001%22%5D
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

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

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