Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflation
Primary Purpose
COVID 19, SARS-CoV 2, Pneumonia
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Mavrilimumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID 19
Eligibility Criteria
Inclusion Criteria:
Inclusion Criteria (must meet all):
- Written informed consent must be obtained before any assessment is performed
- 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
- Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)
- Increased serum inflammatory marker (CRP > 5 mg/dL)
- Severity of disease warrants inpatient hospitalization
Exclusion Criteria:
- Onset of COVID-19 symptoms >14 days
- Age < 18 years-old
- Hospitalized >7 days
- Mechanically ventilated
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
- 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
- Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks
- Chronic or recent corticosteroid use > 10 mg/day
- 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
- Enrolled in another investigational study using immunosuppressive therapy
- Known hypersensitivity to mavrilimumab or any of its excipients
- In the opinion of the investigator, unable to comply with the requirements to participate in the study
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
Sites / Locations
- University of CincinnatiRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mavrilimumab
Placebo
Arm Description
Mavrilimumab treatment infusion
Placebo infusion
Outcomes
Primary Outcome Measures
Primary Outcome Measure:
Proportion of subjects alive and off oxygen at day14
Secondary Outcome Measures
Secondary Outcome Measures:
Proportion of subjects alive and without respiratory failure at 28 days
Full Information
NCT ID
NCT04492514
First Posted
July 28, 2020
Last Updated
July 28, 2020
Sponsor
Kristin Hudock
Collaborators
Kiniksa Pharmaceuticals, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04492514
Brief Title
Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflation
Official Title
Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 20, 2020 (Actual)
Primary Completion Date
May 31, 2021 (Anticipated)
Study Completion Date
May 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kristin Hudock
Collaborators
Kiniksa Pharmaceuticals, Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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 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 COVID 19 patients to evaluate for inclusion and exclusion criteria. Participants will then be approached in this standard manner by study investigator and/or coordinator/research nurse.
Research interventions will take place in the hospital in accordance with privacy standards.
The study team in informed on all study procedures and requirements with daily meetings and the opportunity to continuously update through secure channels.
In this multicenter consortium of 4 academic centers, 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. Data analysis and randomization scheme will be performed by the Cleveland Clinic C5 Research, data analysis, and randomization scheme will be performed by one site, Cleveland Clinic C5 Research.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID 19, SARS-CoV 2, Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Model Description
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Particiapnt, Care Provider, Investigator, Outcomes Assessor)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mavrilimumab
Arm Type
Experimental
Arm Description
Mavrilimumab treatment infusion
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo infusion
Intervention Type
Drug
Intervention Name(s)
Mavrilimumab
Other Intervention Name(s)
KPL-301
Intervention Description
treatment infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
Placebo infusion
Primary Outcome Measure Information:
Title
Primary Outcome Measure:
Description
Proportion of subjects alive and off oxygen at day14
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Secondary Outcome Measures:
Description
Proportion of subjects alive and without respiratory failure at 28 days
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Inclusion Criteria (must meet all):
Written informed consent must be obtained before any assessment is performed
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
Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)
Increased serum inflammatory marker (CRP > 5 mg/dL)
Severity of disease warrants inpatient hospitalization
Exclusion Criteria:
Onset of COVID-19 symptoms >14 days
Age < 18 years-old
Hospitalized >7 days
Mechanically ventilated
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
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
Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks
Chronic or recent corticosteroid use > 10 mg/day
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
Enrolled in another investigational study using immunosuppressive therapy
Known hypersensitivity to mavrilimumab or any of its excipients
In the opinion of the investigator, unable to comply with the requirements to participate in the study
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristin Hudock, MD
Phone
513-803-7819
Email
hudockkn@ucmail.uc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Autumn Cresie
Phone
513-558-0337
Email
studeran@ucmail.uc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Hudock, MD
Organizational Affiliation
University of Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristin Hudock, MD
Phone
513-803-7819
Email
hudockkn@ucmail.uc.edu
First Name & Middle Initial & Last Name & Degree
Autumn Cresie
Phone
513-558-0337
Email
studeran@ucmail.uc.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33754144
Citation
Cremer PC, Abbate A, Hudock K, McWilliams C, Mehta J, Chang SY, Sheng CC, Van Tassell B, Bonaventura A, Vecchie A, Carey B, Wang Q, Wolski KE, Rajendram P, Duggal A, Wang TS, Paolini JF, Trapnell BC; MASH-COVID study group. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-e418. doi: 10.1016/S2665-9913(21)00070-9. Epub 2021 Mar 17.
Results Reference
derived
Learn more about this trial
Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflation
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