NCT04590586.

Methods	Drug name: apremilast, lanadelumab, zilucoplan Trial design: phase 3, randomised, quadruple blind platform trial Identifiers: NCT04590586 Target sample size: 1400 participants Planned completion date: August 2021
Participants	Setting Inpatient Multicentre Eligibility criteria Inclusion criteria Adults (≥ 18 years of age) with active SARS‐CoV‐2 infection confirmed by laboratory tests and/or point‐of‐care tests. A score of Grade 2, 3, 4 or 5, as defined by an 8‐point ordinal scale Male participants: must agree to use contraception during the treatment period and for at least 6 weeks after the last dose of study treatment and refrain from donating sperm during this period Female participants: not pregnant, not breastfeeding Ability to provide informed consent signed by the study participant or LAR Ability and willingness to participate in telephone/telemedicine follow‐up visits if needed Exclusion criteria Participant has any condition for which participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol‐specified assessments Stage 4 severe chronic kidney disease or requiring dialysis Screening 12‐lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) ≥ 500 ms Anticipated transfer to another hospital that is not a study centre within 72 hours Participants who are currently pregnant or who are not willing to discontinue breastfeeding Participants participating in another clinical study of an investigational medicinal product or other unapproved (or investigational) treatment for COVID‐19 Active tuberculosis or a history of incompletely treated tuberculosis Active, uncontrolled systemic bacterial or fungal infection(s)
Interventions	Intervention Apremilast (orally) Lanadelumab (IV) Zilucoplan (SC) injection in the abdomen, thigh, or upper arm Comparator placebo for each substance
Outcomes	Efficacy outcomes All‐cause mortality at up to 30 days: planned at up to 60 days: planned Clinical progression/improvement of symptoms: planned Length of hospital stay: planned Admission to ICU: not planned Length of ICU stay: planned Quality of life, including fatigue: not planned Viral clearance: not planned Safety outcomes Number of participants with grade 3 and grade 4 AEs: planned Number of participants with SAEs: planned Additional study outcomes Number of participants who achieve oxygen‐free recovery at day 29 Worst post‐baseline score on the 8‐point ordinal scale of clinical severity status Number of participants who experience one or more treatment‐emergent adverse events (TEAEs)
Notes	Funding: Amgen