Study of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Standard of care; Apremilast; Apremilast placebo; Lanadelumab; Lanadelumab placebo; Zilucoplan; Zilucoplan placebo
Intervention description: Standard of care (SoC) treatment for COVID-19 infection in line with institutional practice. The SoC may change as new information becomes available about treating COVID-19.; Apremilast administered orally as a tablet.; Matching apremilast placebo administered orally as a tablet.; Lanadelumab administered as an intravenous (IV) infusion.; Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.; Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.; Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
Intervention MeSH terms: Thalidomide; Apremilast; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 515.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2

Summary:

      The primary objective of this study is to evaluate the time to confirmed clinical recovery in
      participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for
      efficacy and safety, with candidate agents being added to and/or removed from the study on an
      ongoing basis, depending on the results of their evaluation.
    

Eligibility criteria:

        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).