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Trial record 4 of 5 for:    mavrilimumab in severe COVID-19

Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation

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ClinicalTrials.gov Identifier: NCT04447469
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : March 9, 2021
Sponsor:
Information provided by (Responsible Party):
Kiniksa Pharmaceuticals, Ltd.

Tracking Information
First Submitted Date  ICMJE June 23, 2020
First Posted Date  ICMJE June 25, 2020
Last Update Posted Date March 9, 2021
Actual Study Start Date  ICMJE July 27, 2020
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2021)
  • Cohort 1: Proportion of Participants Alive and Free of Mechanical Ventilation at Day 29 [ Time Frame: Day 29 ]
    Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO).
  • Cohort 2: Mortality Rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who have died by Day 29.
Original Primary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15 [ Time Frame: Day 15 ]
    Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
  • Cohort 2: Mortality Rate at Day 15 [ Time Frame: Day 15 ]
    Mortality rate is defined as the proportion of participants who die.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2021)
  • Cohort 1: Time to 2-point clinical Improvement by Day 29 [ Time Frame: By Day 29 ]
    Defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. Participants who die before Day 29 will be censored at Day 30. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 1: Time to return to room air or discharge by Day 29 [ Time Frame: By Day 29 ]
    Defined as time from randomization to the start date of breathing room air (NIAID score ≥ 5), or discharge from the hospital, whichever occurs first. Participants who die before Day 29 will be censored at Day 30.
  • Cohort 1: Mortality rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who die.
  • Cohort 2: Time to 1-point clinical improvement by Day 29 [ Time Frame: By Day 29 ]
    Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 29 will be censored at Day 30.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • Cohort 1: Time to Return to Room Air by Day 15 [ Time Frame: up to Day 15 ]
    Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 1: Time to 2-point Clinical Improvement by Day 15 [ Time Frame: up to Day 15 ]
    Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 1: Mortality Rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who die.
  • Cohort 1: Time to 1-Point Clinical Improvement by Day 15 [ Time Frame: up to Day 15 ]
    Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 2: Mortality Rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who die.
  • Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15 [ Time Frame: Day 15 ]
    Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
  • Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29 [ Time Frame: Day 29 ]
    Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
  • Cohorts 1 and 2: Time to Return to Room Air by Day 29 [ Time Frame: up to Day 29 ]
    Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 2: Time to 2-point Clinical Improvement by Day 15 [ Time Frame: up to Day 15 ]
    Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29 [ Time Frame: up to Day 29 ]
    Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29 [ Time Frame: up to Day 29 ]
    Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 1: Respiratory Failure-Free Survival by Day 15 [ Time Frame: up to Day 15 ]
    Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
  • Cohort 1: Respiratory Failure-Free Survival by Day 29 [ Time Frame: up to Day 29 ]
    Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
  • Cohort 1: Proportion of Participants Who Return to Room Air by Day 15 [ Time Frame: up to Day 15 ]
    Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29 [ Time Frame: up to Day 29 ]
    Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohort 1: Mortality Rate at Day 15 [ Time Frame: Day 15 ]
    Mortality rate is defined as the proportion of participants who die.
  • Cohorts 1 and 2: Overall Survival by Day 29 [ Time Frame: up to Day 29 ]
    Overall survival is defined as time from date of randomization to the date of death.
  • Cohorts 1 and 2: Clinical Status Over Time [ Time Frame: Days 4, 8, 15, 22, and 29 ]
    Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
  • Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90 [ Time Frame: through Day 90 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation
Official Title  ICMJE A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation
Brief Summary Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
Detailed Description The Phase 2 portion of the study will evaluate the efficacy and safety of 2 dose levels of mavrilimumab relative to placebo (standard of care) in participants who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with x-ray/computed tomography (CT) evidence of bilateral pneumonia and active or recent signs of hyperinflammation (fever or clinical laboratory results indicative of hyper-inflammation). The Phase 3 portion is intended to confirm Phase 2 efficacy and safety findings. In both Phase 2 and Phase 3, participants will be enrolled into 2 cohorts: Cohort 1 will include non-intubated, hospitalized participants who require supplemental oxygen to maintain oxygen saturation (SpO2) ≥ 92% (ie, "non-ventilated" participants); Cohort 2 will include hospitalized participants for whom mechanical ventilation was recently initiated (ie, "ventilated" participants). Following Screening, enrolled participants in each cohort will be randomized 1:1:1 to receive one of 2 mavrilimumab dose levels, or placebo as a single intravenous (IV) infusion (Day 1). Participants will undergo primary study assessments through Day 29 and will be followed for safety through Day 90.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID
Intervention  ICMJE
  • Drug: mavrilimumab
    anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])
    Other Name: (KPL-301; CAM3001)
  • Other: Placebo
    matching placebo
Study Arms  ICMJE
  • Active Comparator: 10 mg/kg (Cohort 1)
    Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
    Intervention: Drug: mavrilimumab
  • Active Comparator: 6 mg/kg (Cohort 1)
    Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
    Intervention: Drug: mavrilimumab
  • Placebo Comparator: Placebo (Cohort 1)
    Non-mechanically ventilated participants administered placebo as a single IV infusion
    Intervention: Other: Placebo
  • Active Comparator: 10 mg/kg (Cohort 2)
    Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
    Intervention: Drug: mavrilimumab
  • Active Comparator: 6 mg/kg (Cohort 2)
    Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
    Intervention: Drug: mavrilimumab
  • Placebo Comparator: Placebo (Cohort 2)
    Mechanically ventilated participants administered placebo as a single IV infusion
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 5, 2021)
588
Original Estimated Enrollment  ICMJE
 (submitted: June 24, 2020)
573
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Subject (or legally authorized representative) is able and willing to provide informed consent, which includes compliance with study requirements and restrictions listed in the consent form
  • Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization
  • Hospitalized for SARS-CoV-2
  • Bilateral pneumonia on chest x-ray or computed tomography
  • Clinical laboratory results indicative of hyper-inflammation
  • Cohort 1: Receiving any form of oxygenation or NIV to maintain SpO2 ≥ 92% and not-intubated (examples include nasal cannula, face mask, venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation)
  • Cohort 2: Recently ventilated with mechanical ventilation prior to randomization

Key Exclusion Criteria:

  • Onset of COVID-19 symptoms or positive COVID-19 test result > 14 days prior to randomization
  • Hospitalized > 7 days prior to randomization
  • Need for invasive mechanical ventilation (Only for Cohort 1)
  • Need for ECMO
  • Serious prior or concomitant illness that in the opinion of the Investigator precludes the subject from enrolling in the trial
  • Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12 months, non-cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-IL-6 receptor [eg, 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, mycophenolate mofetil (MMF), or other immunosuppressant (except for corticosteroids) within 4 weeks prior to randomization
  • Corrected QT interval Fridericia's formula (QTcF) on Screening electrocardiogram (ECG) ≥500 ms
  • Enrolled in another investigational study of a medical intervention
  • Life expectancy less than 48 hours
  • Known human immunodeficiency virus infection (regardless of immunological status), known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus positivity
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kiniksa Clinical Research Team (781) 431-9100 clinicaltrials@kiniksa.com
Listed Location Countries  ICMJE Brazil,   Chile,   Peru,   South Africa,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04447469
Other Study ID Numbers  ICMJE KPL-301-C203
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The Sponsor will review IPD requests proposals from qualified researchers
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: IPD requests will be accepted after publication of the primary data manuscript
Access Criteria: IPD access will be provided to qualified academic researchers pending the Sponsor's review of the proposed research, including scientific novelty, review of the analytical and publication plans, funding source of the proposed research, any potential conflicts of interest, and institutional capabilities to perform the planned research.
Responsible Party Kiniksa Pharmaceuticals, Ltd.
Study Sponsor  ICMJE Kiniksa Pharmaceuticals, Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kiniksa Pharmaceuticals, Ltd.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP