Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04399980
Recruitment Status : Active, not recruiting
First Posted : May 22, 2020
Last Update Posted : October 6, 2020
Sponsor:
Collaborator:
Kiniksa Pharmaceuticals, Ltd.
Information provided by (Responsible Party):
Paul Cremer, M. D., The Cleveland Clinic

Brief 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.

Condition or disease Intervention/treatment Phase
COVID 19 SARS-CoV 2 Pneumonia Drug: Mavrilimumab Drug: Placebos Phase 2

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 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
Actual Study Start Date : May 20, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Intervention
Treatment infusion
Drug: Mavrilimumab
Treatment infusion
Other Name: KPL-301

Placebo Comparator: Control
Placebo infusion
Drug: Placebos
Placebo infusion
Other Name: Control




Primary Outcome Measures :
  1. Proportion of subjects alive and off of oxygen at day 14 [ Time Frame: Day 14 ]
    Number of subjects alive and off of oxygen


Secondary Outcome Measures :
  1. Proportion of subjects alive at 28 days [ Time Frame: Day 28 ]
    Number of subjects that are alive

  2. Proportion of subjects alive and without respiratory failure at 28 days [ Time Frame: Day 28 ]
    Number of subjects alive and without respiratory failure



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04399980


Locations
Layout table for location information
United States, Florida
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Ohio
Cleveland Clinic Health System
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Kiniksa Pharmaceuticals, Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Paul C Cremer, M. D. The Cleveland Clinic
Layout table for additonal information
Responsible Party: Paul Cremer, M. D., Principal Investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04399980    
Other Study ID Numbers: IND 149324
IRB 20-523 ( Other Identifier: Cleveland Clinic IRB )
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Pneumonia
Respiratory Insufficiency
Inflammation
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Respiration Disorders
Mavrilimumab
Antirheumatic Agents