Initial preliminary findings from the Papa Giovanni XXIII Hospital sponsored SISCO ( Siltuximab In Serious COVID-19 ) Study, based on a pre-planned data analysis on 24 March 2020, were presented.
Siltuximab is an interleukin (IL)-6 targeted monoclonal antibody approved by the U.S. Food and Drug Administration ( FDA ) and the European Medicines Agency ( EMA ) for the treatment of patients with multicentric Castleman disease ( MCD ) who are human immunodeficiency virus ( HIV ) negative and human herpesvirus-8 ( HHV-8 ) negative ( also known as idiopathic MCD; iMCD ).
Siltuximab is under investigation for COVID-19 patients who have developed serious respiratory complications, the leading cause of morbidity and mortality.
The interim data, presented from the first 21 patients treated with Siltuximab and followed for up to 7 days, show that one-third ( 33%, n=7 ) of patients experienced a clinical improvement with a reduced need for oxygen support and 43% ( n=9 ) of patients saw their condition stabilise, indicated by no clinically relevant changes.
Combined, this means that over three-quarters of patients treated with Siltuximab ( 76%, n=16 ) had either stable or improved disease at this interim analysis.
A worsening of the disease was seen in 3 ( 14% ) patients whilst 1 ( 5% ) patient died and 1 ( 5% ) experienced a cerebrovascular event.
C-Reactive Protein ( CRP ) levels, a marker of systemic inflammation, declined from baseline through to day 5 following treatment with Siltuximab in all patients with sufficient recorded values ( 100%, 16/16 ).
This level of reduction was maintained in those patients ( 100%, 16/16 ) 7 days after receiving treatment with Siltuximab.
Reduction in CRP is considered a robust surrogate for indicating the efficacy of IL-6 inhibition.
The majority ( 90%, 19/21 ) of patients presented with fever at baseline, 13/21 ( 62% ) with a dry cough and 15/21 ( 71% ) with dyspnoea.
Partial pressure of arterial oxygen ( PaO2 ) to percentage of inspired oxygen ( FiO2 ), otherwise known as the P/F ratio or lung function, and IL-6 had out of normal ranges at baseline in the majority of patients with a median P/F ratio of 127 ( excluding those more than 300 and indicating Acute Respiratory Distress Syndrome [ ARDS ] and median peripheral IL-6 levels of 140 pg/mL ( range 113-239 pg/mL ).
Serum CRP was elevated in all patients at baseline with a median of 23 mg/dL ( range 10-43 mg/dL ).
SISCO study represents the data collection and analysis of a series of patients treated under an ongoing emergency compassionate use protocol.
The study is investigating two cohorts retrospectively, hospitalised patients prior to admission to an intensive care unit ( ICU ) or patients already requiring intensive care, versus controls.
Primary endpoints are reduction in the need of invasive ventilation, time spent in ICU or 30-day mortality.
Emerging evidence suggests that some patients with COVID-19 may respond with overproduction of IL-6, an inflammatory cytokine, leading to a cytokine storm when the immune system becomes over-stimulated and attacks the patient’s own body.
Elevated IL-6 levels are associated with severity of disease and can lead to serious lung complications and/or ARDS. Therefore, direct targeting of this cytokine may improve clinical outcomes in these critically ill patients.
The SISCO study has enrolled a total of 25 patients with confirmed SARS-CoV-2 infection ( COVID-19 ) and respiratory complications of which preliminary data is presented from the first 21 treated with Siltuximab.
All patients in the study were treated with Siltuximab at a dose of 11mg/kg infused over 1 hour with a second dose possible at physician discretion.
Of the 21 patients treated with Siltuximab, 5 received a second dose ( 5/21; 24% ) 48-72 hours following the initial infusion.
The majority of patients were male ( 18/21, 86% ) with ages ranging from 48 to 75 years.
The most prevalent comorbidities in this group of patients were: hypertension in 43% ( 9/21 ), cardiovascular disease in 19% ( 4/21 ), diabetes in 24% ( 5/21 ) of patients, respectively. ( Xagena )
Fonte: EUSA Pharma, 2020