Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation

August 4, 2021 updated by: Virginia Commonwealth University

Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation

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.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

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, data analysis, and randomization scheme will be performed by one site, Cleveland Clinic C5 Research.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intervention
Treatment infusion
Treatment infusion
Other Names:
  • KPL-301
Placebo Comparator: Control
Placebo infusion
Placebo infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Subjects Alive and Off of Oxygen at Day 14
Time Frame: 14 days
Number of subjects alive and off of oxygen
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects Alive and Without Respiratory Failure at 28 Days
Time Frame: 28 days
Number of subjects alive and without respiratory failure
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2020

Primary Completion (Actual)

November 30, 2020

Study Completion (Actual)

November 30, 2020

Study Registration Dates

First Submitted

July 7, 2020

First Submitted That Met QC Criteria

July 7, 2020

First Posted (Actual)

July 9, 2020

Study Record Updates

Last Update Posted (Actual)

August 11, 2021

Last Update Submitted That Met QC Criteria

August 4, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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