Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation
Condition: COVID-19; Sars-CoV2; Pneumonia
MeSH terms: COVID-19; Pneumonia; Respiratory Insufficiency; Inflammation
Intervention: Mavrilimumab; Placebos
Intervention description: Treatment infusion; Placebo infusion
Intervention MeSH terms: Mavrilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled
      study is to demonstrate that early treatment with mavrilimumab prevents progression of
      respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological
      features of hyper-inflammation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent must be obtained before any assessment is performed

          2. Documented COVID19 pneumonia defined as positive SARS-CoV2 test AND abnormalities/
             infiltrates on chest x-ray or computed tomography AND active fever or documented fever
             within 24-48 hours or ongoing anti-pyretic use to suppress fever

          3. Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)

          4. Increased serum inflammatory marker (CRP > 5 mg/dL)

          5. Severity of disease warrants inpatient hospitalization

        Exclusion Criteria:

          1. Onset of COVID-19 symptoms >14 days

          2. Age < 18 years-old

          3. Hospitalized >7 days

          4. Mechanically ventilated

          5. Serious concomitant illness which in the opinion of the investigator precludes the
             patient from enrolling in the trial, including (but not limited to):

               -  History of immunodeficiency (congenital or acquired)

               -  Neutropenia (absolute neutrophil count <1,500/mm3)

               -  History of solid-organ or bone marrow transplant

               -  History of current systemic autoimmune or autoinflammatory disease(s) requiring
                  systemic immune-modulating drugs

               -  History of myeloproliferative disorder or active malignancy receiving cytotoxic
                  chemotherapy

               -  Pre-existing severe pulmonary disease (i.e. steroid dependent asthma, COPD on
                  home oxygen, or other restrictive/obstructive lung disease requiring home oxygen)

               -  Pre-existing severe left ventricular systolic dysfunction (i.e. LVEF <35%)

               -  Known or suspected active tuberculosis (TB), latent TB, or history of
                  incompletely treated TB or at high risk for latent TB (from exposure or prior
                  incarceration)

               -  History of active or latent viral hepatitis (i.e. Hepatitis B or C)

               -  Concomitant uncontrolled systemic bacterial or fungal infection

               -  Concomitant viral infection other than COVID-19 (e.g. Influenza, other
                  respiratory viruses)

               -  History of chronic liver disease with portal hypertension

               -  History of end-stage renal disease on chronic renal replacement therapy

          6. Recent treatment with cell-depleting biological therapies (e.g., anti-CD20) within 12
             months, cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF],
             anakinra, anti-Interleukin [IL]-6 receptor [e.g. tocilizumab], or abatacept) within 8
             weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within
             12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, or
             mycophenolate mofetil (MMF) within 4 weeks

          7. Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks

          8. Chronic or recent corticosteroid use > 10 mg/day

          9. Pregnant. Breast-feeding women are eligible with the decision to continue or
             discontinue breast-feeding during therapy taking into account the risk of infant
             exposure, the benefits of breast-feeding to the infant, and benefits of treatment to
             the mother

         10. Enrolled in another investigational study using immunosuppressive therapy

         11. Known hypersensitivity to mavrilimumab or any of its excipients

         12. In the opinion of the investigator, unable to comply with the requirements to
             participate in the study

         13. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing of investigational drug. Such methods include:

               -  Total abstinence (when this is in line with the preferred and usual lifestyle of
                  the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks
                  before taking study treatment. In case of oophorectomy alone, only when the
                  reproductive status of the woman has been confirmed by follow up hormone level
                  assessment

               -  Male sterilization (at least 6 months prior to screening). For female subjects on
                  the study, the vasectomized male partner should be the sole partner for that
                  subject

               -  Use of oral, (estrogen and progesterone), injected or implanted hormonal methods
                  of contraception or placement of an intrauterine device (IUD) or intrauterine
                  system (IUS), or other forms of hormonal contraception that have comparable
                  efficacy (failure rate <1%), for example hormone vaginal ring or transdermal
                  hormone contraception