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

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

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

Study Overview

• Status: Completed
• Conditions: COVID
• Intervention / Treatment: Drug: mavrilimumab; Other: Placebo

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-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
• Enrollment (Actual): 814
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Belém, Brazil, 66093-904
    • Hospital Adventista de Belem
  • Fortaleza, Brazil, 60192-340
    • IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará
  • São José, Brazil, 15090-000
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • São Paulo, Brazil, 01323-020
    • Hospital Alemao Oswaldo Cruz
  • Bahia
    • Salvador, Bahia, Brazil, 40170-130
      • Hospital Cardio Pulmonar
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30380-472
      • Hospital Luxemburgo - Associação Mário Penna
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59025-050
      • CPCLIN - Centro de Pesquisas Clínicas
  • Rio Grande Do Sul
    • Lajeado, Rio Grande Do Sul, Brazil, 95900-000
      • Hospital Bruno Born
  • Sao Paulo
    • Botucatu, Sao Paulo, Brazil, 18618-686
      • UPECLIN - Unidade de Pesquisa Clínica
    • Campinas, Sao Paulo, Brazil, 13060-080
      • IPECC - Instituto de Pesquisa Clínica de Campinas
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 65470-000
      • Hospital Das Clinicas Da Faculdade De Medicina De Ribeirao Preto da Universidade de Sao Paulo
• Chile
  • Santiago, Chile, 8380456
    • Hospital Clínico Universidad de Chile
  • Santiago, Chile, 7550000
    • Clinica Las Condes
• Peru
  • Bellavista, Peru, 07011
    • Hospital Nacional Alberto Sabogal Sologuren
  • Lima Cercado, Peru, 15082
    • Essalud - Hospital de Emergencias Grau
  • San Martín De Porres, Peru, 15102
    • Hospital Nacional Cayetano Heredia
  • San Miguel, Peru, 15088
    • Clinica Providencia
• South Africa
  • Bloemfontein, South Africa, 9301
    • Iatros International
  • Cape Town, South Africa, 7530
    • Tiervlei Trial Center
  • George, South Africa, 6529
    • TASK Eden
  • Pretoria, South Africa, 0181
    • Into Research - Little Company of Mary Medical Center
  • Rustenburg, South Africa, 0299
    • Limpopo Clinical Research Initiative
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • University of Cape Town - Lung Institute
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Diego, California, United States, 92110
      • SHARP Health Care
  • Illinois
    • Chicago, Illinois, United States, 60644
      • Affinity Health
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Clinic Hospitalists
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / 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 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	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 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	Other: Placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 29
Cohort 1, Phase 3: 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.	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.	Day 29
Cohort 2, Phase 3: Percentage of Participants Who Died by Day 29	Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.	Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	Day 29

Collaborators and Investigators

• Sponsor: Kiniksa Pharmaceuticals International, plc
• Collaborators: Kiniksa Pharmaceuticals, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2020
• Primary Completion (Actual): November 12, 2021
• Study Completion (Actual): January 14, 2022

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; pneumonia; hyper-inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Pneumonia; Inflammation; Antirheumatic Agents; Mavrilimumab
• Other Study ID Numbers: KPL-301-C203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Sponsor will review IPD requests proposals from qualified researchers
• IPD Sharing Time Frame: IPD requests will be accepted after publication of the primary data manuscript
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No