Lanadelumab in Bradykinin Angioedema

Study Overview
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Brief Summary
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A multicenter observational study aiming to evaluate the efficacy of kallikrein inhibition by lanadelumab in patients with bradykinin- angioedema

Detailed Description
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The bradykinin-angioedema (AE-BK) is characterized by recurrent and unpredictable episodes of swelling; it can be disabling and disfiguring and the attacks affecting the larynx can be life-threatening. The clinical symptoms depend on accumulation of bradykinin (BK), a vasoactive peptide responsible for vasodilation and increase of vascular leakage. BK formation depends on activation of the kallikrein-kinin cascade leading to uncontrolled generation of plasma kallikrein and subsequent proteolysis of high molecular-weight kininogen (HK). Lanadelumab is a fully human monoclonal antibody inhibitor of plasma kallikrein, thereby preventing BK production; it represents an attractive therapeutic strategy for BK-AE prophylaxis. The aim of this study is to evaluate the kallikrein inhibition by assessing the levels of cleaved HK and the immunogenicity of the lanadelumab.

Official Title
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Evaluation of the Efficacy of Kallikrein Inhibition by Lanadelumab for Patients With Bradykinin Angioedema: a Cohort Study

Conditions
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Angioedema

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female >18 years old Patient with hereditary or acquired angioedema Patient treated by lanadelumab Patient whose the biological explorations have been carried out or will be carried out at Laboratory of Immunology of CHUGA Informed consent is obtained from the participant Exclusion Criteria: Absence of biological material at T0 and M3 (stored for routine analysis) Person under guardianship or curatorship Female who is pregnant, nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Hereditary or Acquired Angioedema<br>Participants older than 18 years that are diagnosed with Hereditary or Acquired Angioedema and treated by lanadelumab. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of the kallikrein inhibition by lanadelumab in patients with bradykinin-angioedema | Levels of cleaved HK measured by Western Blot | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of kallikrein inhibition by lanadelumab in patients with bradykinin-angioedema between T0 and the others visits | Levels of cleaved HK as measured by Western Blot Ratio Day 7/ Day 0, Ratio Month 6/ Day 0, Ratio Month 12/ Day (and if possible Month 24/ Day 0) of the levels of cleaved HK as measured by Western Blot - SE2: antidrug antibodies in the sera of patients at Months 3, 6, 12 (and if possible Month 24). | Day 7; 6, 12 and if possible 24 months | 
| Immunogenicity of lanadelumab | Levels of antidrug antibodies in the sera of patients | Months 3, 6, 12 (and 24 if possible) | 
| Evaluation of therapeutic escape | Increase/absence of decrease of the number of attacks during lanadelumab administration | Months 3, 6, 12 and if possible 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kallikrein, Kininogen, Bradykinin, Lanadelumab