Preliminary results of the clinical trial of CRX-675, a toll-like receptor 4 ( TLR4 ) agonist, in subjects allergic to ragweed showed that the drug is safe.
The study was a randomized, blinded, placebo-controlled trial of single doses of CRX-675 given intranasally prior to intranasal challenges with ragweed allergen.
The primary objective of this clinical trial was to evaluate the safety of CRX-675 given as a single intranasal dose.
Subjects were randomized to either a CRX-675 group ( 4 escalating dose levels n=12/group ) or a placebo group ( n=4/dose group; total n=16 ).
Each subject in the study completed a series of direct nasal challenges with increasing concentrations of ragweed allergen to determine an allergen dose that would result in a 30 percent reduction in nasal volume ( defined as the PD30 dose ) during the screening period of the study.
Two weeks later, each subject was challenged with their assigned PD30 dose of ragweed allergen and then monitored for safety and nasal volume ( congestion ), as well as total nasal symptom scores, to establish their baseline allergic response to ragweed.
Fourteen days later, subjects were treated with either placebo or one of four single intranasal doses of CRX-675 ( 2, 20, 100 or 200 micrograms ), 24 hours prior to a second PD30 ragweed challenge.
Safety measurements, nasal congestion and total nasal symptom scores were evaluated following ragweed challenge.
In order to assess any delayed effects of CRX-675, subjects were re-challenged with ragweed allergen 14 days after being treated with CRX-675 or placebo and evaluated for allergic responses.
There were no serious or severe adverse events reported.
The majority of the adverse events were mild ( grade 1 ) and either considered unrelated to the drug being evaluated or resolved without intervention.
The adverse event profile of CRX-675-treated subjects was similar to that of placebo-treated subjects.
These results confirm that intranasal administration of CRX-675 is safe.
Other exploratory responses to CRX-675 were assessed by evaluating the percent change in nasal congestion and nasal symptom scores post ragweed challenge.
There were no consistent trends for improvement in nasal congestion post ragweed challenge for the CRX-675 treatment groups beyond those observed in the placebo group.
There was a consistent decrease in nasal symptom scores in the 100ug CRX-675 treatment group when compared to the placebo group.
This trend in reduction of nasal symptom scores for the 100ug CRX-675 treatment group occurred both one day and 14 days after CRX-675 treatment when challenged with ragweed.
The total nasal symptom scores were too low post ragweed challenge in the 20ug and 200ug CRX-675 treatment groups to adequately assess an effect at those dose levels in this study.
As a result, no dose response relationship was detected.
Source: Corixa, 2005