Study of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

Inclusion Criteria:

- Adults (≥18 years of age) with active severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) infection confirmed by laboratory tests and/or point of care tests (eg,
commercial or public health assay, which is approved for emergency use). If no
diagnostic test results are available that have been obtained during the previous 72
hours, then a test should be performed as part of the screening assessment.

- A score of Grade 2 (hospitalized, on invasive mechanical ventilation or ECMO), Grade 3
(hospitalized, on noninvasive ventilation or high-flow oxygen devices), Grade 4
(hospitalized, requiring supplemental oxygen), or Grade 5 (hospitalized, not requiring
supplemental oxygen, requiring ongoing medical care [COVID-19 related or otherwise]),
as defined by an 8 point ordinal scale.

- Male participants:

- A male participant 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:

- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least 1 of the following conditions applies:

- Not a woman of childbearing potential (WOCBP). OR

- A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 6 weeks after the last dose of study treatment.

- Ability to provide informed consent signed by the study participant or legally
authorized representative.

- Ability and willingness to participate in telephone/telemedicine follow-up visits if
needed.

- Zilucoplan only: Antibiotic prophylaxis: all participants must be willing to take
antibiotic prophylaxis concomitantly, starting with the first dose of zilucoplan or
placebo.

Exclusion Criteria:

- Participant has any condition for which, in the opinion of the Investigator,
participation would not be in the best interest of the participant (eg, compromise
their well-being) or that could prevent, limit, or confound the protocol-specified
assessments (eg, participants unable to swallow study medication tablets).

- Stage 4 severe chronic kidney disease or requiring dialysis.

- Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to
Fridericia correction (QTcF) ≥ 500 ms.

- Anticipated transfer to another hospital that is not a study center 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).

- Apremilast only: Current treatment with apremilast, or another agent of similar
mechanism of action, for any indication within 1 week prior to first dose of
investigational product.

- Apremilast only: Concurrent use at screening or randomization of cytochrome P450
(CYP)3A inducers (eg, rifampin, phenobarbital, carbamazepine) within 1 week prior to
first dose of investigational product.

- Apremilast only: Known hypersensitivity to apremilast or any excipients in
formulation.

- Lanadelumab only: Known or suspected hypersensitivity to lanadelumab or any of its
excipients.

- Lanadelumab only: Previous (within 3 months prior to baseline) or current use of
immunomodulators (eg, methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis
factor [TNF] α inhibitor, Janus kinase [JAK] inhibitor, alpha-integrin inhibitor).

- Lanadelumab only: Known or suspected venous thromboembolism.

- Lanadelumab only: Previous (within 3 months [or 5 half-lives, whichever is greater] of
screening) or current use of plasma kallikrein (pKal) inhibitor or bradykinin receptor
blocker.

- Zilucoplan only: Participants with unresolved or suspected infection with Neisseria
meningitidis or a past history of N. meningitidis (eg, in a complement-deficient
patient).