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Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04447469
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
Kiniksa Pharmaceuticals, Ltd.

Study Description
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Brief Summary:
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).

Condition or disease Intervention/treatment Phase
COVID Drug: mavrilimumab Other: Placebo Phase 2 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) and have x-ray/computerized tomography (CT) evidence of bilateral pneumonia, active or recent fever, and 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 573 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 10 mg/kg (Cohort 1)
Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
 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)
Active Comparator: 6 mg/kg (Cohort 1)
Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
 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)
Placebo Comparator: Placebo (Cohort 1)
Non-mechanically ventilated participants administered placebo as a single IV infusion
 Other: Placebo
matching placebo
Active Comparator: 10 mg/kg (Cohort 2)
Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
 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)
Active Comparator: 6 mg/kg (Cohort 2)
Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
 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)
Placebo Comparator: Placebo (Cohort 2)
Mechanically ventilated participants administered placebo as a single IV infusion
 Other: Placebo
matching placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. Cohort 2: Mortality Rate at Day 15 [ Time Frame: Day 15 ]
    Mortality rate is defined as the proportion of participants who die.


Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. Cohort 1: Mortality Rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who die.

  4. 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.


  5. Cohort 2: Mortality Rate at Day 29 [ Time Frame: Day 29 ]
    Mortality rate is defined as the proportion of participants who die.

  6. 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.

  7. 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

  8. 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.


  9. 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.


  10. 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.


  11. 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.


  12. 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.

  13. 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

  14. 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.


  15. 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.


  16. Cohort 1: Mortality Rate at Day 15 [ Time Frame: Day 15 ]
    Mortality rate is defined as the proportion of participants who die.

  17. 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.

  18. 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.

  19. Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90 [ Time Frame: through Day 90 ]

Eligibility Criteria
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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.


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

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
  • Active fever or recently documented fever within 72 hours prior to randomization
  • 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, 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), COVID-19-immune plasma, or other immunosuppressant within 4 weeks prior to randomization
  • corrected QT interval Fridericia's formula (QTcF) on Screening electrocardiogram (ECG) ≥450 ms
  • Chronic or recent (within 7 days prior to randomization) corticosteroid use >10 mg/day
Contacts and Locations
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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): NCT04447469


Contacts
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Contact: Kiniksa Clinical Research Team (781) 431-9100 clinicaltrials@kiniksa.com

Locations
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United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095-1690
Contact: Tisha Wang, MD         
United States, Louisiana
Tulane Medical Center Not yet recruiting
New Orleans, Louisiana, United States, 70112
Contact: Joshua Denson, MD         
United States, Texas
University of Texas Health Sciences Recruiting
Houston, Texas, United States, 77030
Contact: Mohammad Madjid, MD         
Sponsors and Collaborators
Kiniksa Pharmaceuticals, Ltd.
More Information
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Responsible Party: Kiniksa Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT04447469    
Other Study ID Numbers: KPL-301-C203
First Posted: June 25, 2020    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Sponsor will review IPD requests proposals from qualified researchers
Supporting Materials: Study Protocol
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kiniksa Pharmaceuticals, Ltd.:
COVID-19
pneumonia
hyper-inflammation
Additional relevant MeSH terms:
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Pneumonia
Inflammation
Pathologic Processes
Lung Diseases
 Respiratory Tract Diseases
Respiratory Tract Infections
Mavrilimumab
Antirheumatic Agents