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

Kiniksa Pharmaceuticals International, plc814 enrolled

Overview

Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).

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-mechanically ventilated, hospitalized participants who require supplemental oxygen to maintain oxygen saturation (SpO2) ≥ 92% (ie, "non-mechanically ventilated" participants); Cohort 2 will include hospitalized participants for whom mechanical ventilation was recently initiated (ie, "mechanically 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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

814

Conditions

COVID

Interventions

mavrilimumabDRUG

anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G \[IgG4\])

PlaceboOTHER

matching placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. Consent must be performed per institutional regulations. * Age of ≥ 18 years * Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization * Hospitalized for SARS-CoV-2 (2019-nCoV) * Bilateral pneumonia on chest x-ray or computed tomography * Clinical laboratory results indicative of hyper-inflammation within 7 days prior to randomization * Cohort 1: Receiving any form of non-invasive ventilation OR oxygenation to maintain SpO2 ≥ 92% and non-mechanically ventilated (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 beginning within 48 hours prior to randomization Key Exclusion Criteria: * Onset of COVID-19 symptoms \> 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. Medications that become standard of care for COVID-19 and/or receive emergency use authorization may be allowed after discussion with the medical monitor. * If subject is receiving or has received hydroxychloroquine within 3 months prior to screening visit, a corrected QT interval by Federicia method (QTcF) on Screening electrocardiogram (ECG) ≥500ms is exclusionary. If subject has a pacemaker, this criterion does not apply. * Enrolled in another investigational study of a medical intervention within 30 days prior to randomization. Participation in open label trials involving investigational treatments for COVID-19 may be allowed upon approval by the Sponsor. * Life expectancy less than 48 hours, in the opinion of the Investigator * Known human immunodeficiency virus infection (regardless of immunological status), known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus positivity

Locations (32)

Outcomes

Primary Outcomes

Cohort 1, Phase 2: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29

Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status was evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Participants whose clinical outcome met a NIAID score of 2 were considered as using mechanical ventilation. The NIAID score 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.

Time frame: Day 29

Cohort 1, Phase 3: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29

Time frame: Day 29

Cohort 2, Phase 2: Percentage of Participants Who Died by Day 29

Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Cohort 1, Phase 2: Time to 2-point Clinical Improvement by Day 29

Defined as time from randomization to a 2-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever came first. Participants who died before Day 29 were censored at Day 30. Kaplan-Meier method used to estimate the survival functions for each treatment arm. The NIAID score 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.

Time frame: Day 29

Phase 2, Cohort 1: Time to Return to Room Air or Discharge by Day 29

Defined as time from randomization to breathing room air (NIAID score ≥ 5), or discharge from the hospital, whichever came first. Participants who died before Day 29 were censored at Day 30.

Time frame: Day 29

Phase 2, Cohort 1: Percentage of Participants Who Die by Day 29

95% CI were calculated using Clopper-Pearson exact method based on the beta distribution.

Time frame: Day 29

Phase 2, Cohort 2: Time to 1-Point Clinical Improvement by Day 29

Defined as time from randomization to the date of a 1-point improvement on the NIAID score 8-point ordinal scale or discharge from the hospital, whichever occurred first, by Day 29. Participants who did not have 1-point improvement on the NIAID nor discharge from the hospital were censored at the date of the last NIAID 8-point ordinal scale assessment on/before Day 29. Participants who died were censored at Day 32.

Time frame: Day 29

Phase 3, Cohort 1: Percentage of Participants Who Died at Day 29

Mortality rate at day 29 is the proportion of subjects who die by day 29. 95% CI were calculated using Clopper-Pearson exact method based on the beta distribution.

Time frame: Day 29

Phase 3, Cohort 1: Ventilation-Free Survival (Time to Ventilation or Death) by Day 29

Time to ventilation or death by Day 29 was defined as time (in days) from randomization to the date of death or start date of using mechanical ventilation (NIAID score ≤ 2) by Day 29. Participants who never had NIAID score ≤ 2 by Day 29 were censored at last assessment date of NIAID 8-point ordinal scale.

Time frame: Day 29

Phase 3, Cohort 1: Overall Survival by Day 29

Overall survival was defined as time from randomization to the date of death on/before Day 29. Participants who did not have a death record by Day 29 were censored at last date known alive on/before Day 29.

Time frame: Day 29

Phase 3, Cohort 2: Time to 1-point Clinical Improvement by Day 29

Defined as time from randomization to the date of a 1-point improvement on the NIAID 8-point ordinal scale or discharge from the hospital, whichever occurred first, by Day 29. Participants who did not have 1-point improvement on the NIAID nor discharge from the hospital were censored at the date of the last NIAID 8-point ordinal scale assessment on/before Day 29. Participants who died were censored at Day 35.

Time frame: Day 29