As of today, numerous monoclonal antibodies are being studied with the SARS-CoV-2 spike protein as main target of action.

The studies available show absence of benefit in hospitalized patients in an advanced stage of the disease, while the use in earlier settings has been associated with a reduction in viral load with preliminary evidence of a lower use of health resources (hospitalization, access to emergency rooms). No information is available on more relevant clinical outcomes such as ICU access, intubation or mortality.

The guidelines of the main international learned societies (IDSA and NIH) do not recommend the routine use of monoclonal antibodies in clinical practice.

In order to verify whether monoclonal antibodies can represent a real therapeutic option in preventing the progression of COVID-19 in patients in an early stage of the disease, the Italian Medicines Agency (AIFA) deems it useful to promote and support a randomized clinical trial. To ensure access to the medicinal product and financial support to conduct a randomized multi-arm clinical trial, we ask to receive a randomized clinical trial protocol which shall consider the following issues:

• Population: trials should include SARS-CoV-2 positive subjects in early stages of the disease not hospitalized (for example, subjects who have access to the emergency room) with or without comorbidities which may worsen the prognosis of COVID-19.
• Intervention: the intervention is represented by monoclonal antibodies in an advanced stage of clinical development. Currently, the protocol should include at least the following two products: bamlanivimab (Eli-Lilly) and casirivimab/imdevimab (Regeneron). Any other antibodies may be authorized following a prior exchange with the Agency. AIFA shall guarantee the availability of the medicines under study.
• Comparator: trials should include at least three study arms comparing the two monoclonal products versus one SOC arm; the latter must take into account AIFA’s recommendations on COVID-19 medicines.
• Outcome: trials shall have clinical outcomes represented, for example, by disease progression/hospitalization. The protocol shall include a detailed presentation of the minimum difference in efficacy that the trial will be able to highlight with respect to SOC and between individual antibodies. Virological or biomarker-based assessments are considered secondary outcomes.
• Organizational aspects: requests for clinical trials shall include a feasibility plan considering: the actual possibility of recruiting an adequate number of subjects; the availability of an adequate management infrastructure (e.g., a platform for patient registration and data collection); the ability to ensure good recruitment, also taking into account the complexity associated with the methods of administering medicines. The possibility shall also be positively evaluated of extending participation to all centres showing a concrete interest in the trial, as well as a possible international extension of the trial.
• Request for funding: The protocol shall provide for a detailed economic plan. The costs of the trial will be covered by the Agency as regards both the medicines and the costs of conducting the trial.

AIFA shall select the clinical trial protocol, with the support of external experts. The selected trial shall be assessed by AIFA’s Scientific-Technical Committee (CTS) and by the Ethics Committee of the National Institute for Infectious Diseases "L. Spallanzani".

The deadline for submitting the protocol is 1 February 2021 at 12.00pm CET, by sending the documentation to: bandomonoclonali@aifa.gov.it.

Further information and details relating to the clinical trial protocol and to the methods of submission will be announced by 20 January 2021 on the Agency website.

Published on: 15 January 2021