RGD Reference Report - Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. - Rat Genome Database

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

Authors: Casale, TB  Kessler, J  Romero, FA 
Citation: Casale TB, etal., Ann Allergy Asthma Immunol. 2006 Oct;97(4):454-6.
RGD ID: 7800738
Pubmed: PMID:17069098   (View Abstract at PubMed)
DOI: DOI:10.1016/S1081-1206(10)60934-9   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
allergic rhinitis treatmentIDA 7800738 RGD 
allergic rhinitis treatmentISOTLR4 (Homo sapiens)7800738; 7800738 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information