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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.

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) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 588 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
Actual Study Start Date : July 27, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

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




Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. 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.


  2. 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.

  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 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.



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
  • 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

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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Sponsors and Collaborators
Kiniksa Pharmaceuticals, Ltd.
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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: March 9, 2021
Last Verified: March 2021
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