AstraZeneca said it will initiate a randomized, global clinical trial to assess the potential of Calquence (acalabrutinib) in the treatment of the exaggerated immune response (cytokine storm) associated with COVID-19 infection in severely ill patients.
The trial design is based on scientific evidence supporting the role of the Bruton’s tyrosine kinase (BTK) pathway in the production of inflammatory cytokines and on encouraging early clinical data. Calquence is a next-generation, highly selective BTK inhibitor currently used to treat certain types of blood cancers.
The trial, called CALAVI, is based on early clinical data with Calquence demonstrating that a decrease in inflammation caused by BTK inhibition appears to reduce the severity of COVID-19-induced respiratory distress. The goal of the trial is to evaluate the efficacy and safety of adding Calquence to best supportive care (BSC) to reduce mortality and the need for assisted ventilation in patients with life-threatening COVID-19 symptoms.
“We can confirm that NCI is involved with administration of off-label use of acalabrutinib in a small number of selected patients with severe COVID-19,” NCI said in a statement. “While some clinical benefit has been observed in select patients with advanced lung disease caused by COVID-19, it is premature to conclude that it will provide benefit across patients with advanced lung disease due to the very early and limited use of this agent in COVID-19 at this time.
“Thus, it will be necessary to gather data from randomized, controlled clinical trials in order to understand the best and safest treatment options for patients. NCI’s chief concern is the safety and well-being of patients, caregivers, and researchers, and staff.”
This large, multicenter, global, randomized trial uses a two-part patient-centric design developed in record time to accelerate data capture and analysis. Part One evaluates the addition of Calquence to BSC versus BSC alone in patients hospitalised with COVID-19 who are not in the intensive care unit. Part Two evaluates the addition of Calquence to BSC in a cohort of patients in the ICU.
“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,” José Baselga, executive vice president and head of Oncology R&D at Astrazeneca, said in a statement. “This is the fastest launch of any clinical trial in the history of AstraZeneca.”
The CALAVI trial is expected to open for enrollment in the coming days in the U.S. and several countries in Europe. Wyndham H. Wilson, of NCI, will serve as the principal investigator of the trial.
“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, chief of NCI’s Lymphoid Malignancies Branch and senior investigator of the CALAVI trial, said in a statement. “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.”
