Angioedema
Conditions
Keywords
Kallikrein, Kininogen, Bradykinin, Lanadelumab
Brief summary
A multicenter observational study aiming to evaluate the efficacy of kallikrein inhibition by lanadelumab in patients with bradykinin- angioedema
Detailed description
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.
Interventions
None listed
Sponsors
University Hospital, Grenoble
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the efficacy of the kallikrein inhibition by lanadelumab in patients with bradykinin-angioedema | 3 months | Levels of cleaved HK measured by Western Blot |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the efficacy of kallikrein inhibition by lanadelumab in patients with bradykinin-angioedema between T0 and the others visits | Day 7; 6, 12 and if possible 24 months | 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). |
| Immunogenicity of lanadelumab | Months 3, 6, 12 (and 24 if possible) | Levels of antidrug antibodies in the sera of patients |
| Evaluation of therapeutic escape | Months 3, 6, 12 and if possible 24 | Increase/absence of decrease of the number of attacks during lanadelumab administration |
Countries
France
Contacts
Primary ContactFederica Defendi, PhD
Backup ContactCharlotte Kevorkian-Verguet
Outcome results
None listed