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History of Changes for Study: NCT04447469
Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation
Latest version (submitted March 16, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 24, 2020 None (earliest Version on record)
2 July 19, 2020 Recruitment Status, Study Status and Contacts/Locations
3 July 28, 2020 Contacts/Locations and Study Status
4 August 13, 2020 Study Status and Contacts/Locations
5 October 6, 2020 Contacts/Locations and Study Status
6 November 16, 2020 Contacts/Locations and Study Status
7 March 5, 2021 Outcome Measures, Study Status, Contacts/Locations, Eligibility, Study Design and Study Description
8 December 13, 2021 Recruitment Status, Contacts/Locations, Study Status, Outcome Measures, Study Design and Eligibility
9 March 16, 2022 Recruitment Status and Study Status
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Study NCT04447469
Submitted Date:  June 24, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: KPL-301-C203
Brief Title: Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation
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
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2020
Overall Status: Not yet recruiting
Study Start: June 2020
Primary Completion: February 2021 [Anticipated]
Study Completion: April 2021 [Anticipated]
First Submitted: June 23, 2020
First Submitted that
Met QC Criteria:
June 24, 2020
First Posted: June 25, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 24, 2020
Last Update Posted: June 25, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Kiniksa Pharmaceuticals, Ltd.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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) 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.
Open or close this module Conditions
Conditions: COVID
Keywords: COVID-19
pneumonia
hyper-inflammation
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2/Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 6
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 573 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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 Names:
  • (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 Names:
  • (KPL-301; CAM3001)
Placebo Comparator: Placebo (Cohort 1)
Non-mechanically ventilated participants administered placebo as a single IV infusion
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 Names:
  • (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 Names:
  • (KPL-301; CAM3001)
Placebo Comparator: Placebo (Cohort 2)
Mechanically ventilated participants administered placebo as a single IV infusion
Placebo
matching placebo
Open or close this module Outcome Measures
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 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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
Open or close this module Contacts/Locations
Central Contact Person: Kiniksa Clinical Research Team
Telephone: (781) 431-9100
Email: clinicaltrials@kiniksa.com
Locations: United States, Louisiana
Tulane Medical Center
New Orleans, Louisiana, United States, 70112
Contact:Contact: Joshua Denson, MD
Open or close this module IPDSharing
Plan to Share IPD: Yes
The Sponsor will review IPD requests proposals from qualified researchers
Supporting Information:
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.
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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