Clinical Trials

The CALIMA trial will evaluate the safety and effectiveness of benralizumab in actively reducing exacerbations in patients with uncontrolled asthma. The study will also assess the effect of benralizumab on lung function, asthma symptoms and other asthma control measures, as well as emergency room and hospitalisation rates due to asthma. Trial participants will be classified in the trial based on blood eosinophils measured through a simple blood test. They will be administered benralizumab subcutaneously via a pre-filled syringe.
In addition to CALIMA, the Windward programme will include two pivotal exacerbation trials for benralizumab added to high- (SIROCCO) or medium- (PAMPERO) dose inhaled corticosteroids plus a long-acting beta agonist; an oral corticosteroid-reducing trial (ZONDA); and a long-term safety trial (BORA). These trials are designed to provide additional information about benralizumab in patients with severe uncontrolled asthma.

 

* On September 5, 2016, AstraZeneca announced that benralizumab, its first biologic respiratory medicine met primary and key secondary endpoints in pivotal trials for severe asthma. Results from pivotal Phase III trials presented at the European Respiratory Society (ERS) International Congress demonstrated that adding benralizumab to standard-of-care medicine significantly reduced exacerbations and improved lung function and asthma symptoms in severe asthma patients with an eosinophilic phenotype, as indicated by the presence of eosinophils in their blood. The SIROCCO and CALIMA trials evaluated the effect of two dosing regimens of benralizumab 30mg administered in 4-week and 8-week regimens as add-on therapy to standard-of-care medicine across primary and key secondary endpoints. Results showed:
* reductions in the annual rate of asthma exacerbations (up to 51%)
* improvement in lung function (change in FEV1 of up to 159 mL), which was seen at 4 weeks after the first benralizumab dose and sustained throughout the treatment period

* improvement in asthma symptoms, such as wheeze, cough, chest tightness and shortness of breath
The outcomes were demonstrated for the 8-week dosing regimen, with no additional benefit observed with 4-week dosing, which may support less-frequent dosing. In addition, post-hoc analysis showed greater improvements in exacerbation rate reduction, FEV1 and total asthma symptom scores in patients with a history of more frequent asthma exacerbations. Detailed results were published  in The Lancet for the Phase III SIROCCO and CALIMA trials.
The adverse event frequency was similar between benralizumab-treated patients versus placebo-treated patients for both SIROCCO and CALIMA (72% and 74% for all benralizumab treated patients vs. 76% and 78% for placebo-treated patients observed in SIROCCO and CALIMA, respectively). The most common (?5%) adverse events in benralizumab-treated patients observed in SIROCCO were asthma, nasopharyngitis, upper respiratory infection, headache, bronchitis, sinusitis, influenza and pharyngitis; and in CALIMA were nasopharyngitis, asthma, bronchitis, upper respiratory tract infection, headache and sinusitis. The data from the SIROCCO and CALIMA trials will be included in regulatory submissions for benralizumab that are planned for the US and EU later in 2016.
* On May 17, 2016, AstraZeneca announced that benralizumab was well tolerated and achieved the primary endpoint in two pivotal Phase III registrational trials (SIROCCO and CALIMA), demonstrating significant reductions in the annual asthma exacerbation rate compared to placebo. The trials evaluated the efficacy and safety of two dose regimens of benralizumab as an add-on therapy for severe uncontrolled asthma with eosinophilic inflammation in adults and adolescents 12 years of age and older. In SIROCCO and CALIMA, the primary analysis population included patients on high-dose inhaled corticosteroids (ICS) plus long-acting ?2-agonist (LABA) with a baseline blood eosinophil count ? 300 cells/microliter. Patients were randomised to receive benralizumab 30mg every 4 weeks; 30mg every 4 weeks for the first three doses followed by 30mg every 8 weeks; or placebo. The safety and tolerability findings for benralizumab were generally consistent with those reported in previous trials. Results from the SIROCCO and CALIMA trials will be presented at a future medical meeting. Regulatory submissions in the US and EU are anticipated in the second half of 2016.

* On October 30, 2013, AstraZeneca has announced the start of the Phase III Windward programme for benralizumab, a potential treatment for severe uncontrolled asthma developed by MedImmune. The goal of CALIMA, the first study in the Windward programme, is to determine whether benralizumab reduces the number of exacerbations in patients with severe asthma that remains uncontrolled, despite receiving high doses of inhaled corticosteroids in combination with a second controller such as a long-acting beta agonist.
Initiation of this trial is based on results from the Phase IIb asthma study, which showed that patients with elevated eosinophils on benralizumab had a statistically significant reduction in exacerbation rate compared to placebo, as well as improvements in lung function and asthma symptoms. The efficacy and safety data from this trial supported the progression of benralizumab into our Phase III programme. These results are expected to be shared at a scientific conference in the first half of 2014.