AstraZeneca announced it will be conducting a global clinical trial, CALAVI, to examine the impact of adding acalabrutinib to best supportive care for patients who are severely ill with the COVID-19 infection.
AstraZeneca plans to conduct a global clinical trial to assess the effect of acalabrutinib (Calquence) on the exaggerated immune response of patients who are severely ill with the coronavirus disease 2019 (COVID-19) infection, according to a press release.
The trial design was based on strong scientific and early clinical data on the Bruton’s tyrosine kinase (BTK) pathway and its role in the production of inflammatory cytokines. The trial hopes to evaluate safety and efficacy of adding acalabrutinib to best supportive care in an attempt to reduce mortality and assisted ventilation requirements for patients with strong COVID-19 symptoms.
“With this trial we are responding to the novel insights of the scientific community and hope to demonstrate that adding Calquence to best supportive care reduces the need to place patients on ventilators and improves their chances of survival,” JosÃ© Baselga, executive vice president of Oncology R&D, said in a press release. “This is the fastest launch of any clinical trial in the history of AstraZeneca.”
Early clinical data with acalabrutinib suggested that a decrease in inflammation caused by BTK inhibitors reduces the severity of COVID-19-induced respiratory distress. Acalabrutinib is a highly selective BTK inhibitor currently used to treat certain types of blood cancers, such as mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This large, multicenter, global, randomized trial, named CALAVI, is based on this data.
The trial will implement a 2-part approach, with the first part evaluating the addition of acalabrutinib to best supportive care vs best supportive care alone for patients not in intensive care units. The second part will evaluate the addition of acalabrutinib to best supportive care in a group of patients admitted to intensive care units for COVID-19 related symptoms.
More, the development of this two-part approach was done in historic time to accelerate data collection and analysis. Part 1 is randomized 2:1 for patients hospitalized, but not on ventilation. Part 2 focuses more closely on patients with severe symptoms as a result of COVID-19 and are being cared for in intensive care units. The primary endpoint analyzes the use of assisted ventilation.
“Given the well documented role of the protein BTK in regulating inflammation, it is possible that inhibiting BTK with acalabrutinib could provide clinical benefit in patients with advanced COVID-19 lung disease,” Louis M. Staudt, MD, PhD, chief of the lymphoid malignancies branch at the National Cancer Institute, said in a press release. “As with all new treatments, it will be necessary to gather data from clinical trials in order to understand the best and safest treatment options for patients.”
Most COVID-19 cases show mild symptoms, but some are more severe and require hospitalization due to pneumonia. The COVID-19 infection continues to sweep across the globe, with more than 1.9 million confirmed cases and 123,000 deaths as of April 14.
AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19 [news release]. Published April 14, 2020. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazeneca-initiates-calavi-clinical-trial-with-calquence-against-covid-19.html. Accessed April 14, 2020.