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

Angioedema Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04444895
• Other study ID #: TAK-743-3001
• Secondary ID: 2019-004823-20jR
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2021
• Est. completion date: May 5, 2023

Study information

• Verified date: June 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: May 5, 2023
• Est. primary completion date: May 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Angioedema

Intervention

Drug:
• Lanadelumab
Rollover participants will receive 300 mg of lanadelumab solution in a PFS SC injection once Q2W or Q4W for 26 consecutive weeks.

Locations

Country	Name	City	State
Canada	Ottawa Allergy Research Corporation	Ottawa	Ontario
Canada	Clinique Specialisee en Allergie de la Capitale	Québec	Quebec
France	Hôpital Saint-Antoine	Paris
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet pt	Frankfurt	Hessen
Germany	Klinikum rechts der Isar der TU	Muenchen	Bayern
Hungary	Semmelweis Egyetem	Budapest
Italy	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	A.O. Ospedali riuniti Villa Sofia - Cervello,	Palermo	Palermo Palermo
Italy	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona	Salerno
Japan	Clover Hospital	Fujisawa-shi	Kanagawa-Ken
Japan	Hiroshima University Hospital	Hiroshima-shi	Hiroshima-Ken
Japan	Kobe University Hospital	Kobe-shi	Hyogo-Ken
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	UMC Utrecht	Utrecht
Poland	NZOZ Homeo Medicus, Poradnia Alergologiczna	Bialystok
Poland	"ALL-MED" Specjalistyczna Opieka Medyczna Filia	Wroclaw
Spain	Hospital Universitario Cruces	Barakaldo	Vizcaya
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United States	University of Michigan	Ann Arbor	Michigan
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Institute for Asthma & Allergy, P.C.	Chevy Chase	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Bernstein Clinical Research Center, LLC	Cincinnati	Ohio
United States	Asthma and Allergy Associates, PC	Colorado Springs	Colorado
United States	Optimed Research, LTD	Columbus	Ohio
United States	Kanarek Allergy, Asthma and Immunology	Overland Park	Kansas
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	UCSD Angioedema Center	San Diego	California
United States	Medical Research of Arizona	Scottsdale	Arizona
United States	Seattle Allergy & Asthma Research Institute	Seattle	Washington
United States	Allergy and Asthma Clinical Research Inc	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Shire	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From start of the study up to follow-up (Day 196)
Secondary	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.	Day 0 through Day 182
Secondary	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.	Day 0 through Day 182
Secondary	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.	Day 0 through Day 182
Secondary	Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab	Pharmacokinetic plasma concentrations of lanadelumab will be assessed.	Day 0, 84, 140 and 182
Secondary	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.	Day 0, 84, 140 and 182
Secondary	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.	Day 0, 84, 140 and 182
Secondary	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).	Day 0, 28, 84, 140 and 182
Secondary	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.	Day 0 through Day 168

External Links

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