Clinical trial NCT04444895: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Angioedema
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2020-06-24
Enrollment: 73
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period
timeFrame: From Day 0 up to Day 182
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up
timeFrame: From Day 183 up to Day 196
Secondary outcomes:
measure: Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
timeFrame: From Day 0 up to Day 182
measure: Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
timeFrame: From Day 0 up to Day 182
measure: Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182
timeFrame: From Day 0 up to Day 182
measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
timeFrame: Predose on Days 0, 84, and 140 and postdose on Day 182
measure: Plasma Kallikrein (pKal) Activity
timeFrame: Predose on Days 0, 84, and 140 and postdose on Day 182
measure: Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma
timeFrame: Predose on Days 0, 84, and 140 and postdose on Day 182
measure: Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period
timeFrame: Baseline (Day 0) up to end of treatment period (Day 182)
measure: Number of Participants With Any Pause During Injection
timeFrame: Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants Who Switched Dosing Regimen
timeFrame: From Day 0 up to Day 196
measure: Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
timeFrame: From Day 0 up to Day 182
measure: Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
timeFrame: From Day 0 up to Day 182
measure: Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen
timeFrame: From Day 0 up to Day 182
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: San Diego
country: United States
facility: UCSD Angioedema Center
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research Inc
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Overland Park
country: United States
facility: Kanarek Allergy, Asthma and Immunology
state: Kansas
city: Chevy Chase
country: United States
facility: Institute for Asthma & Allergy, P.C.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Seattle
country: United States
facility: Seattle Allergy & Asthma Research Institute
state: Washington
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corporation
state: Ontario
city: Québec
country: Canada
facility: Clinique Specialisee en Allergie de la Capitale
state: Quebec
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU
state: Bayern
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet pt
state: Hessen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Palermo
country: Italy
facility: A.O. Ospedali riuniti Villa Sofia - Cervello,
state: Palermo Palermo
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-Ken
city: Kobe-shi
country: Japan
facility: Kobe University Hospital
state: Hyogo-Ken
city: Fujisawa-shi
country: Japan
facility: Clover Hospital
state: Kanagawa-Ken
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Bialystok
country: Poland
facility: NZOZ Homeo Medicus, Poradnia Alergologiczna
city: Wroclaw
country: Poland
facility: "ALL-MED" Specjalistyczna Opieka Medyczna Filia
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
affiliation: Takeda Development Center Americas
name: Study Director
role: STUDY_DIRECTOR
References: