Efficacy and Safety Study of IV Ravulizumab in Patients With COVID-19 Severe Pneumonia
Condition: COVID-19 Severe Pneumonia; Acute Lung Injury; Acute Respiratory Distress Syndrome; Pneumonia, Viral
MeSH terms: COVID-19; Pneumonia; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Syndrome
Intervention: Ravulizumab; BSC
Intervention description: Weight-based doses of ravulizumab were administered intravenously on Days 1, 5, 10, and 15.; Participants received medications, therapies, and interventions per standard hospital treatment protocols.
Intervention MeSH terms: Ravulizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: acute lung injury; acute respiratory distress syndrome; antibodies, monoclonal, humanized; COVID-19; hospitalization; pneumonia; severe pneumonia; severe acute respiratory syndrome; severe acute respiratory syndrome coronavirus 2; randomized controlled study; ravulizumab; respiratory distress syndrome, adult; Ultomiris; viral

Summary:

      This study evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of
      ravulizumab administered in adult participants with coronavirus disease 2019 (COVID-19)
      severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Participants
      were randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3
      of the participants) or BSC alone (1/3 of the participants). BSC consisted of medical
      treatment and/or medical interventions per routine hospital practice.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males or female participants ≥ 18 years of age and ≥ 40 kilograms at the time of
             providing informed consent.

          2. Confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection (for
             example, via polymerase chain reaction and/or antibody test) presenting as severe
             COVID-19 requiring hospitalization.

          3. Severe pneumonia, acute lung injury, or acute respiratory distress syndrome confirmed
             by computed tomography or X-ray at Screening or within the 3 days prior to Screening,
             as part of the participant's routine clinical care.

          4. Respiratory distress requiring mechanical ventilation, which can be either invasive
             (requiring endotracheal intubation) or noninvasive (with continuous positive airway
             pressure or bilevel positive airway pressure).

          5. Female participants of childbearing potential and male participants with female
             partners of childbearing potential must follow protocol specified contraception
             guidance for avoiding pregnancy for 8 months after treatment with the study drug.

        Exclusion Criteria:

          1. Participant was not expected to survive for more than 24 hours.

          2. Participant was on invasive mechanical ventilation with intubation for more than 48
             hours prior to Screening.

          3. Severe pre-existing cardiac disease (that is, New York Heart Association Class 3 or
             Class 4, acute coronary syndrome or persistent ventricular tachyarrhythmias).

          4. Participant had an unresolved Neisseria meningitidis infection.

          5. Used the following medications and therapies:

               -  Current treatment with a complement inhibitor or

               -  Intravenous immunoglobulin within 4 weeks prior to randomization on Day 1

          6. Treatment with investigational therapy in a clinical study within 30 days before
             randomization, or within 5 half-lives of that investigational therapy, whichever was
             greater. Exceptions:

               -  Investigational therapies were allowed if received as part of BSC through an
                  expanded access protocol or emergency approval for the treatment of COVID-19.

               -  Investigational antiviral therapies (such as remdesivir) were allowed even if
                  received as part of a clinical study.

          7. Female participants who were breastfeeding or who have a positive pregnancy test
             result at Screening.

          8. History of hypersensitivity to any ingredient contained in the study drug, including
             hypersensitivity to murine proteins.

          9. Participant who was not currently vaccinated against Neisseria meningitidis, unless
             the participant agrees to receive prophylactic treatment with appropriate antibiotics
             for at least 8 months after the last infusion of study drug or until at least 2 weeks
             after the participant receives vaccination against Neisseria meningitidis.