Heterogeneity in COVID‐19 Convalescent Plasma Clinical Trials

Abstract

Due to the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, clinical trial (CT) research for efficacy and safety evaluation of convalescent plasma (CP) accelerated globally. In trial planning and approval, clinical researcher and regulatory agencies worldwide are challenged by limited evidence from the use of convalescent plasma in previous outbreaks of viral diseases and by different possible study approaches. We analyzed CT designs to identify potential opportunities for data aggregation and to facilitate generation of decision-relevant evidence.CP therapy has a long-standing history in the post-exposure prophylaxis and treatment of infectious diseases, including outbreaks of various respiratory infections, such as the 2002-2004 severe acute respiratory syndrome-coronavirus (SARS-CoV) pandemic, the 2009 H1N1 influenza virus pandemic, and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic. Unfortunately, evidence of its efficacy from rigorously controlled CTs is still limited. 1 The number of CTs evaluating CP therapy in patients suffering from coronavirus disease has rapidly grown in response to the COVID-19 pandemic in the absence of a vaccine and a specific antiviral therapy. Over 140 CP-CTs have been registered by a COVID-19 specific CT database. 2 Different study concepts and designs are required for a comprehensive evaluation of the quality, efficacy, and safety aspects of CP therapy. The

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients—An Open-Label Phase II Clinical Trial

“…CCP is the second most frequent investigational medicinal product evaluated in COVID-19-related clinical trials, and increasing interest in this form of immunotherapy is documented by the fact that more than 140 clinical trials specifically evaluating CCP in COVID-19 have been registered to date worldwide [ 24 , 25 ]. This study adds to the growing body of evidence supporting the efficacy of high-titer CCP in reducing progression to severe disease [ 19 , 26 , 27 , 28 ] and decreasing mortality [ 2 , 20 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] in inpatients with early COVID-19 and low WHO scores.…”

Too Early to Abandon Convalescent Plasma for Supportive Treatment of COVID-19

“…Normally, in planning clinical trials to support the licensing of medicines, you would aim to define as exactly as possible the investigational drug (composition, dose, and schedule of application) and target disease. In the case of COVID-19, studies have in common the pathogen and CP as investigational treatment, but further details (e.g., duration, stage, and severity of disease and antibody content and dose of CP) are quite heterogeneous [6] .…”