Purpose of the Study
A dose-ranging study was performed to evaluate the safety and efficacy, and pharmacodynamics and pharmacokinetics of CGP 51901, a recombinant monoclonal mouse-human chimeric anti-human immunoglobulin-E (IgE) antibody, in adults with allergic rhinitis. This model was chosen because the cause-effect relationship of antigen exposure and symptoms is well-defined.
One hundred fifty-five patients (mean ages 38.5–42.8 years), who were relatively symptom-free before the annual mountain cedar allergic rhinitis season and met inclusion criteria, were randomly assigned to one of four treatment groups.
This was a multicenter study performed in randomized, blinded, parallel-group fashion. Subjects received 6 biweekly, intravenous doses of placebo, 15, 30, or 60 mg of CGP 51901 beginning before seasonal allergen exposure during the presymptomatic state. At each study visit serum CGP 51901 and free IgE levels were measured at predose, and one-half and 4 hours postdose. At one center serial blood samples were obtained from predose to 240 hours postdose. Subjects also recorded daily nasal symptoms (sneezing, itchy nose, runny nose, and stuffy nose) on a 0 to 3 scale (0 being no symptoms, 3 being severe symptoms). Pollen counts were measured at each center.
One hundred fifty-three subjects completed the trial. All doses were generally well-tolerated; however, 1 subject reported pruritis, generalized urticaria, and chest tightness within 15 minutes of receiving 60 mg of CGP 51901. This episode improved immediately after treatment with epinephrine, nebulized albuterol, and an antihistamine. Subjects categorized as having high (≥85%) and moderate (45%–85%) reductions of free IgE demonstrated the greatest suppression of nasal symptoms. Overall, symptoms appeared to follow pollen counts during the treatment period. The greatest decreases of free IgE levels occurred with higher doses; over half the subjects in the 60 mg dose group had ≥85% reduction of free IgE. Data from pharmacodynamic and pharmacokinetic modeling indicate that a serum CGP 51901 concentration of 5200 ng/ml, maintained throughout the dosing interval with the 60 mg dose only, is sufficient to reduce free IgE by 85% in half the samples analyzed.
Results of this study strongly suggest that reduction of free IgE levels can result in a substantial reduction of allergic rhinitis symptoms.
Although much too early to anticipate approval of CGP 51901 for the treatment of seasonal allergic rhinitis, this study demonstrates that depletion of circulating free IgE levels can prevent or reduce allergic symptoms.