Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study.
Adult
Allergens
/ immunology
Antibodies, Monoclonal
/ therapeutic use
Antigens, Plant
/ immunology
Basophils
/ immunology
Betula
/ immunology
Desensitization, Immunologic
Double-Blind Method
Female
Humans
Immunoglobulin G
/ therapeutic use
Male
Middle Aged
Rhinitis, Allergic, Seasonal
/ immunology
Young Adult
Allergen immunotherapy
Bet v 1
allergic rhinitis
biologics
birch allergy
monoclonal antibodies
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
01
02
2021
revised:
06
05
2021
accepted:
14
05
2021
pubmed:
15
6
2021
medline:
4
3
2022
entrez:
14
6
2021
Statut:
ppublish
Résumé
The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy. Extending these findings, we tested a Bet v 1-specific antibody cocktail in birch-allergic subjects. This was a phase 1, randomized, double-blind, study with 2 parts. Part A administered ascending doses of the Bet v 1-specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults. Part B administered a single subcutaneous 900-mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score response to titrated birch extract nasal allergen challenge and skin prick test (SPT) with birch and alder allergen were assessed at screening and days 8, 29, 57, and 113 (SPT only); basophil activation tests (n = 26) were conducted. Single-dose REGN5713/14/15 significantly reduced total nasal symptom score following birch nasal allergen challenge relative to baseline. Differences in total nasal symptom score areas under the curve (0-1 hour) for subjects treated with REGN5713/14/15 versus those given placebo (day 8: -1.17, P = .001; day 29: -1.18, P = .001; day 57: -0.85, P = .024) and titration SPT with birch difference in area under the curve of mean wheal diameters for subjects treated with REGN5713/14/15 versus placebo (all P < .001) were sustained for ≥2 months; similar results were observed with alder SPT. REGN5713/14/15 was well tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in subjects treated with REGN5713/14/15 versus those given placebo on days 8, 57, and 113 (all P < .01). Single-dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen nasal allergen challenge, potentially offering a new paradigm for the treatment of birch allergy symptoms.
Sections du résumé
BACKGROUND
The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy.
OBJECTIVES
Extending these findings, we tested a Bet v 1-specific antibody cocktail in birch-allergic subjects.
METHODS
This was a phase 1, randomized, double-blind, study with 2 parts. Part A administered ascending doses of the Bet v 1-specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults. Part B administered a single subcutaneous 900-mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score response to titrated birch extract nasal allergen challenge and skin prick test (SPT) with birch and alder allergen were assessed at screening and days 8, 29, 57, and 113 (SPT only); basophil activation tests (n = 26) were conducted.
RESULTS
Single-dose REGN5713/14/15 significantly reduced total nasal symptom score following birch nasal allergen challenge relative to baseline. Differences in total nasal symptom score areas under the curve (0-1 hour) for subjects treated with REGN5713/14/15 versus those given placebo (day 8: -1.17, P = .001; day 29: -1.18, P = .001; day 57: -0.85, P = .024) and titration SPT with birch difference in area under the curve of mean wheal diameters for subjects treated with REGN5713/14/15 versus placebo (all P < .001) were sustained for ≥2 months; similar results were observed with alder SPT. REGN5713/14/15 was well tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in subjects treated with REGN5713/14/15 versus those given placebo on days 8, 57, and 113 (all P < .01).
CONCLUSIONS
Single-dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen nasal allergen challenge, potentially offering a new paradigm for the treatment of birch allergy symptoms.
Identifiants
pubmed: 34126156
pii: S0091-6749(21)00904-0
doi: 10.1016/j.jaci.2021.05.039
pii:
doi:
Substances chimiques
Allergens
0
Antibodies, Monoclonal
0
Antigens, Plant
0
Immunoglobulin G
0
Bet v 1 allergen, Betula
126161-14-6
Banques de données
ClinicalTrials.gov
['NCT03969849']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
189-199Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.