Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis.

Abstract

BACKGROUND:

CRX-675 is an aqueous formulation of a toll-like receptor 4 agonist and an inducer of TH1 responses. Studies in allergic dogs showed that pretreatment with CRX-675 reduced nasal congestion induced by allergen challenge.

OBJECTIVE:

To study the safety of intranasal CRX-675 treatment in patients with seasonal allergic rhinitis.

METHODS:

We conducted a single-center, randomized, double-blind, placebo-controlled, dose-escalating safety trial of single doses of CRX-675 given intranasally before intranasal ragweed challenges. Patients with ragweed-induced seasonal allergic rhinitis received increasing concentrations of ragweed to determine the dose that would result in a 30% reduction in nasal volume (PD30) during screening. Two weeks later, each patient was rechallenged with their assigned PD30 ragweed dose. Fourteen days later, patients were treated with either placebo (n = 16) or CRX-675 (2, 20, 100, or 200 microg intranasally, n = 12 per arm) 24 hours before a subsequent PD30 ragweed challenge. Patients were rechallenged with ragweed 14 days thereafter.

RESULTS:

No serious or severe adverse events were reported. Most adverse events were mild (grade 1) and either were considered unrelated to CRX-675 or resolved without intervention. The adverse event profile of CRX-675-treated patients was similar to that of placebo-treated patients, and no dose-related toxic effects were observed. There was no clear trend in the ability of CRX-675 to inhibit nasal allergen challenge responses, but improvement in nasal symptom scores was observed at 100 microg.

CONCLUSIONS:

This preliminary trial suggests that intranasally applied CRX-675 is safe at the doses tested. Appropriate dosing and timing will ultimately define its potential therapeutic role for allergies.

• Authors: Thomas B Casale, Jean Kessler, Francisco A Romero
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 97 Issue 4 Pg. 454-6 (Oct 2006) ISSN: 1081-1206 [Print] United States
• PMID: 17069098 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Lipid A
• Toll-Like Receptor 4
• monophosphoryl lipid A

Topics

• Administration, Intranasal
• Dose-Response Relationship, Drug
• Drug-Related Side Effects and Adverse Reactions
• Humans
• Immunotherapy, Active
• Lipid A (adverse effects, analogs & derivatives, therapeutic use)
• Rhinitis, Allergic, Seasonal (drug therapy)
• Toll-Like Receptor 4 (agonists, metabolism)