Lanadelumab in Bradykinin Angioedema

Recruiting

• Conditions: Angioedema

• Registration Number: NCT04597944
• Lead Sponsor: University Hospital, Grenoble

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.

Study Timeline

• Study First Submitted: 2020-09-14
• Study Start: 2020-09-18
• Study First Submitted QC: 2020-10-16
• Study First Posted: 2020-10-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-18
• Last Update Posted: 2024-03-19
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2)

Chu Grenoble Alpes; 🇫🇷 Grenoble, France

CHU Rouen; 🇫🇷 Rouen, France