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.
This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is
designed 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.
The study population includes patients who have severe pneumonia, defined as hospitalization
due to Covid-19 with abnormal chest imaging and SpO2 <92% on room air or requirement for
supplemental oxygen.
Enrollment: The study will be performed in approximately 4 months total, starting from the
first patient enrolled with enrollment expected to complete within 2 months.
Follow-up period: The follow-up period is 60 days for each patient enrolled.
A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will
receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator,
clinical team, and subject will be blinded to treatment assignment.
Participants will be identified by regular review of hospitalized COVID19 patients to
evaluate for inclusion and exclusion criteria. Participants will then be approached in the
standard manner by study investigator and coordinator/research nurse.
Research interventions will take place in the hospital in accordance with privacy standards.
The study team is informed on all study procedures and requirements with daily meetings and
the opportunity to continuously update through secure channels.
In this multicenter consortium, each participating site will have their own IND for patients
enrolled at their site. Data collection will occur at each of the 4 academic centers, and
data analysis and randomization scheme will be performed by one site, Cleveland Clinic C5
Research.
Drug: Mavrilimumab
Treatment infusion
Other Name: KPL-301
Drug: Placebos
Placebo infusion
Other Name: Control
Inclusion Criteria (must meet all):
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
Cleveland Clinic Florida
Weston, Florida, United States
Cleveland Clinic Health System
Cleveland, Ohio, United States
Paul C Cremer, M. D., Principal Investigator
The Cleveland Clinic