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

• ClinicalTrials.gov Identifier: NCT04447469
• Recruitment Status: Recruiting
• First Posted: June 25, 2020
• Last Update Posted: November 17, 2020
• Sponsor: Kiniksa Pharmaceuticals, Ltd.
• Information provided by (Responsible Party): Kiniksa Pharmaceuticals, Ltd.

Study Description

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

• 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
• Actual Study Start Date: July 27, 2020
• Estimated Primary Completion Date: February 2021
• Estimated Study Completion Date: April 2021

Arms and Interventions

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

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

• 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

Contacts

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

Locations

United States, California

UCLA Medical Center; Recruiting

Los Angeles, California, United States, 90095

Sharp Health Care; Recruiting

San Diego, California, United States, 92110

United States, Illinois

Affinity Health; Recruiting

Oak Brook, Illinois, United States, 60523

United States, Louisiana

Tulane Medical Center; Recruiting

New Orleans, Louisiana, United States, 70112

United States, Minnesota

Allina Health System; Recruiting

Minneapolis, Minnesota, United States, 55407

United States, Missouri

Mercy Hospital; Recruiting

Springfield, Missouri, United States, 65804

United States, Ohio

University of Cincinnati; Recruiting

Cincinnati, Ohio, United States, 45229

United States, Texas

University of Texas Health Sciences; Recruiting

Houston, Texas, United States, 77030

Brazil

UPECLIN - Unidade de Pesquisa Clínica; Recruiting

Botucatu, Brazil, 18618-686

IPECC - Instituto de Pesquisa Clínica de Campinas; Recruiting

Campinas, Brazil, 13060-080

IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará; Recruiting

Fortaleza, Brazil, 60192-340

Hospital Bruno Born; Recruiting

Lajeado, Brazil, 95900-000

Centro de Pesquisas Clínicas; Recruiting

Natal, Brazil, 59025-050

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; Recruiting

Ribeirão Preto, Brazil, 65470-000

Hospital Cardio Pulmonar; Recruiting

Salvador, Brazil, 40170-130

Hospital Alemão Oswaldo Cruz; Recruiting

São Paulo, Brazil, 01323-020

Chile

Clinica Las Condes; Recruiting

Santiago, Chile, 7550000

Peru

Hospital Essalud Alberto Sabogal Sologuren; Recruiting

Bellavista, Peru, 07011

Essalud - Hospital de Emergencias Grau; Recruiting

Lima Cercado, Peru, 15082

Hospital Nacional Cayetano Heredia; Recruiting

San Martín De Porres, Peru, 15102

Clinica Providencia; Recruiting

San Miguel, Peru, 15088

South Africa

IATROS International; Recruiting

Bloemfontein, South Africa, 9301

Tiervlei Trial Center; Recruiting

Cape Town, South Africa, 7530

TASK Eden; Recruiting

George, South Africa, 6529

Into Research - Little Company of Mary Medical Center; Recruiting

Pretoria, South Africa, 0181

Limpopo Clinical Research Initiative; Recruiting

Rustenburg, South Africa, 0299

Sponsors and Collaborators

Kiniksa Pharmaceuticals, Ltd.

More Information

• Responsible Party: Kiniksa Pharmaceuticals, Ltd.
• ClinicalTrials.gov Identifier: NCT04447469
• Other Study ID Numbers: KPL-301-C203
• First Posted: June 25, 2020
• Last Update Posted: November 17, 2020
• Last Verified: November 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.

• 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:

Pneumonia; Inflammation; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Mavrilimumab; Antirheumatic Agents