Dr. Khalid is a health researcher and science writer with a Ph.D. in clinical research.
The Clinical Trial
A recent entry in ClinicalTrials.gov reveals a randomized controlled phase II study recruiting subjects to evaluate the therapeutic efficacy of clazakizumab for COVID19 infection in comparison to placebo. The study will execute in Cedars-Sinai Medical Center (Los Angeles) with the core objective of determining the potential of clazakizumab in the management of clinically deteriorated cases of COVID19. This clinical trial aims to determine the therapeutic efficacy of clazakizumab in terms of treating COVID-19 infected patients who require mechanical ventilation for their survival. This interleukin-6 drug could probably deal with the COVID-19 cases affected by intense pulmonary manifestations. This open-label trial advocates the intravenous administration of 25mg of clazakizumab with normal saline to the COVID-19 infected patients. This clinical trial also focuses on the measurement of primary outcomes based on unexpected or unusual adverse events associated with the therapeutic use of clazakizumab. The study is designed to check the patient survival rate at 28 days and 60 days of treatment administration. The study will also evaluate the number of patients in need of clazakizumab following their pulmonary decline. The comparative assessment with placebo will determine the reduction in ICU (intensive care unit) days of the COVID-19 patients after clazakizumab therapy. The study will also measure the number of hospital days or total duration required for recovering from COVID19 infection through clazakizumab therapy. This clinical trial hypothesizes the reduction in mechanical ventilation requirement of COVID-19 patients who receive clazakizumab therapy rather than a placebo. This clinical trial allows the recruitment of COVID-19 patients between the ages of 18-100 years. The enrolled patient must not experience the need for mechanical ventilation at the time of their registration in the clinical trial.
The Diagnostic Criteria
The diagnostic criteria for pulmonary involvement adopted by this phase II clinical trial rely on the following conditions.
- A marked reduction in the oxygen saturation level below 94%
- The development of resting respiratory rate tachypnoea with a breathing rate of twenty-five breathes per minute or above
- An elevated C-reactive protein level of above 35 mg/L
- Development of pneumonia (affirmed through radiological imaging)
- Affirmation of COVID-19 infection in body fluid, stool, urine, blood, or respiratory secretions through polymerase chain reaction assay.
- The study does not include pregnant females and lactating mothers
- The study summarily excludes pulmonary tuberculosis patients
- The study excludes all those patients who exhibit any variation in their SGOT or SGPT levels
- The study does not allow the participation of its enrolled COVID-19 patients in other clinical trials
- The study will observe the mechanical ventilation requirement of the COVID-19 patients after 14 days of clazakizumab versus placebo treatment
The Current Knowledgebase of Clazakizumab
The evidence-based clinical literature describes clazakizumab in terms of a monoclonal antibody that blocks the production of IL (interleukin)-6 cytokine. 25-200mg of clazakizumab is presumed to treat the clinical manifestations of active psoriatic arthritis in the absence of conclusive evidence. Clinical trials have also claimed the therapeutic potential of clazakizumab in terms of delaying the late antibody-mediated rejection in patients who receive allografts for their renal function improvement. A clinicall trial in 2015 claimed the therapeutic efficacy of the clazakizumab-methotrexate combination in improving the remission rates in rheumatoid arthritis patients. The anti-inflammatory potential of aglycosylated clazakizumab based on its IL-6 targeting capacity is still under investigation through an array of clinical trials. Interestingly, despite strong evidence of the IL-6 receptor binding ability of clazakizumab, the unavailability of molecular data weakens its therapeutic claims for COVID-19 management. Furthermore, the immunopharmacology of clazakizumab is still not known to the scientific community. Clinical literature provides some clues regarding clazakizumab’s potential for challenging the biological pathways related to myostatin receptors in cancer patients. Clazakizumab’s potential for challenging cancer cachexia is also widely debated in the scientific community. However, these discussions lack substance and so far, no clinical study has provided any conclusive evidence related to the pharmacotherapeutic efficacy of clazakizumab in cancer cases. Clazakizumab’s claim for COVID-19 mitigation is based on its anti-inflammatory potential; however, no evidence is yet available in clinical literature regarding the therapeutic efficacy of this drug in any type of coronavirus infection. The role of clazakizumab in the mitigation of IL-6 signaling pathways is not yet determined by any of the previously conducted clinical studies.
The Baseline for Selecting Clazakizumab
The clinical literature testifies the role of interleukin-6 in terms of establishing chronic inflammation in various disease conditions. IL-6 is also recognized for its deleterious effects on glucose and lipid metabolism. IL-6 triggers the pathophysiological processes based on beta-cell stimulation, T-cells differentiation, and release of proinflammatory cytokines. It is unclear how clazakizumab will influence these biological pathways, particularly the protective effects of IL-6 responsible for triggering trans-signaling pathways that promote the accumulation of various cytokines adapted for proinflammatory interventions. Furthermore, the lack of data on clazakizumab’s effects on signal transducer and activator of transcription proteins and their impact on anti-apoptosis genes also necessitates its clinical trial for COVID-19 infection. The outcomes of clazakizumab trial might selectively guide the development of a potential COVID-19 therapy. Therefore, the simultaneous initiation of parallel studies to comparatively analyze IL-6 blocking potential of clazakizumab with other similar candidates is also required to explore the scope of viable COVID-19 management (single or a combination) therapy. Accordingly, some of the potential candidates of COVID-19 clinical trials include the humanized monoclonal antibodies and nanobodies based on olokizumab, sirukumab, and ALX-0061.
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© 2022 Dr Khalid Rahman