• Pulmonary Clinical Trials
• Asthma

• Pulmonary & Critical Care
• Pulmonary Clinical Trials
• Asthma

Treatment with the A-type CpG oligodeoxynucleotide CYT003-QbG10 did not improve asthma control or lung function in patients with allergic asthma not adequately controlled with inhaled corticosteroids. Thomas Casale, MD, University of South Florida, Tampa, Florida, USA, presented data from the Randomized, Placebo-Controlled, Phase IIb Dose-Finding Study of CYT003-QbG10, a TLR9-Agonist, for Treatment of Uncontrolled Moderate to Severe Allergic Asthma [NCT01673672; Casale T et al. Am J Respir Care Med 2014].

CYT003-QbG10 is an A-type CpG oligodeoxynucleotide that activates toll-like receptor 9 to inhibit T-cell mediated airway inflammation. A previous study demonstrated that CYT003-QbG10 maintained or improved symptom control in patients with allergic asthma that was controlled with an inhaled corticosteroid [Beeh KM et al. J Allergy Clin Immunol 2013]. The purpose of this trial was to determine if treatment with CYT003-QbG10 would achieve similar results in patients with allergenic asthma that was not controlled by inhaled corticosteroids.

In this Phase 2 trial, 365 adults with moderate to severe allergic asthma were randomly assigned to receive 3 different dose levels of CYT003-QbG10 or placebo for 12 weeks. CYT003-QbG10 was administered by subcutaneous injection weekly for the first 4 weeks, then every other week up to 12 weeks. Patients aged 18 to 65 years were eligible if their asthma (Global Initiative Against Asthma steps 3 and 4) was not controlled with standard therapy. The primary outcome was asthma control after 12 weeks, and secondary outcomes included lung function, asthma symptoms, medication score, exacerbation, and quality of life.

Treatment with any dose of CYT003-QbG10 did not significantly change asthma control from baseline compared with placebo, as determined by the Asthma Control Questionnaire (ACQ) score. In addition, there were no significant changes from baseline in lung function or Mini Asthma Quality of Life Questionnaire scores.

Dr. Casale discussed the potential reasons that CYT003-QbG10 failed in this trial, focusing on the differences in study populations between the initial and current study. He noted that the ACQ score and eosinophil count were lower, and lung function was higher, in the patients in the initial study compared with the present study [Beeh KM et al. J Allergy Clin Immunol 2013]. He hypothesized that immune modulators such as CYT003-QbG10 may only benefit certain subpopulations. For example, the initial study demonstrated that CYT003-QbG10 treatment resulted in better outcomes in patients with the Th2-hi phenotype, which encompasses patients with higher eosinophil counts [Beeh KM et al. J Allergy Clin Immunol 2013]. Dr. Casale further differentiated the 2 study populations by pointing out that in the initial study, the improvement in ACQ score occurred when the corticosteroid dose was tapered to a lower dose and then discontinued. In the current study, no additional benefit was seen with the addition of CYT003-QbG10 to inhaled corticosteroids. Therefore, he suggested that CYT003-QbG10 may be most effective in patients who are not being treated for their asthma and that those with uncontrolled asthma represent the wrong patient population for this therapy.

In conclusion, Dr. Casale stated that although CYT003-QbG10 is not effective in patients with uncontrolled allergic asthma on inhaled corticosteroids, it may be effective in patients with allergic asthma who are steroid naïve with the Th2-hi phenotype. However, development of this drug for use in asthma has been discontinued.

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