Biological effects and clinical efficacy of a topical Toll-like receptor 7 agonist in seasonal allergic rhinitis: a parallel group controlled phase IIa study.

Abstract

OBJECTIVE AND DESIGN:

The purpose of the study was to examine effects of pre-treatment with a Toll-like receptor 7 (TLR7) agonist (AZD8848) in allergic rhinitis and to evaluate clinical effects of two dosing regimens.

SUBJECTS:

The study involved 83 patients with allergic rhinitis. Data on effects of AZD8848 on symptoms were analysed with data from a previous study (n = 68) of identical double blind, parallel group design (NCT00770003).

TREATMENT:

The treatment involved intranasal AZD8848 20 µg three times weekly, 60 µg once weekly, or placebo for 5 weeks.

METHODS:

Nasal lavage and plasma were analysed for proof-of-mechanism markers. Daily nasal allergen challenges were given for 7 days, starting 24 h after the final AZD8848 dose. Symptoms were monitored after each challenge and every morning and evening.

RESULTS:

Markers of TLR-activation increased following AZD8848 administration (CXCL10, TNFα, IL-6, IFNγ). Symptoms recorded soon after allergen challenge were reduced up to eight days after the final dose of AZD8848. Morning and evening symptoms were also reduced, and these changes reached statistical significance for morning observations. Adverse effects were more frequent in the 20 µg three times weekly group.

CONCLUSIONS:

Repeated administration of AZD8848 activated TLR7 and produced IFN-induced effects. This was associated with a sustained reduction in allergen responsiveness.

• Authors: Lennart Greiff, Cecilia Ahlström-Emanuelsson, Mikaela Alenäs, Gun Almqvist, Morgan Andersson, Anders Cervin, Jan Dolata, Sam Lindgren, Anders Mårtensson, Barbara Young, Henrik Widegren
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 64 Issue 11 Pg. 903-15 (Nov 2015) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 26342289 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AZD8848
• Allergens
• Anti-Allergic Agents
• Cytokines
• Phenylacetates
• TLR7 protein, human
• Toll-Like Receptor 7
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology, therapeutic use)
• Administration, Topical
• Adolescent
• Adult
• Allergens (immunology)
• Anti-Allergic Agents (pharmacology, therapeutic use)
• Betula (immunology)
• Cytokines (blood, immunology)
• Double-Blind Method
• Female
• Gene Expression (drug effects)
• Humans
• Male
• Middle Aged
• Nasal Lavage Fluid (immunology)
• Phenylacetates (pharmacology, therapeutic use)
• Poaceae (immunology)
• Pollen (immunology)
• Rhinitis, Allergic, Seasonal (blood, drug therapy, immunology)
• Toll-Like Receptor 7 (agonists, immunology)
• Treatment Outcome
• Young Adult