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

Primary Purpose

COVID

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
mavrilimumab
Placebo
Sponsored by
Kiniksa Pharmaceuticals, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID focused on measuring COVID-19, pneumonia, hyper-inflammation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA Medical Center
  • SHARP Health Care
  • Affinity Health
  • Tulane University School of Medicine
  • Allina Health System
  • Mercy Clinic Hospitalists
  • University of Cincinnati
  • Bryn Mawr Hospital
  • University of Texas Health Sciences
  • Hospital Cardio Pulmonar
  • Hospital Luxemburgo - Associação Mário Penna
  • CPCLIN - Centro de Pesquisas Clínicas
  • Hospital Bruno Born
  • UPECLIN - Unidade de Pesquisa Clínica
  • IPECC - Instituto de Pesquisa Clínica de Campinas
  • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
  • Hospital Adventista de Belem
  • IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará
  • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • Hospital Alemão Oswaldo Cruz
  • Clinica Las Condes
  • Hospital Clinico Universidad de Chile
  • Hospital Nacional Alberto Sabogal Sologuren
  • Essalud - Hospital de Emergencias Grau
  • Hospital Nacional Cayetano Heredia
  • Clinica Providencia
  • University of Cape Town - Lung Institute
  • IATROS International
  • Tiervlei Trial Center
  • TASK Eden
  • Into Research - Little Company of Mary Medical Center
  • Limpopo Clinical Research Initiative

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

10 mg/kg (Cohort 1)

6 mg/kg (Cohort 1)

Placebo (Cohort 1)

10 mg/kg (Cohort 2)

6 mg/kg (Cohort 2)

Placebo (Cohort 2)

Arm Description

Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion

Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion

Non-mechanically ventilated participants administered placebo as a single IV infusion

Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion

Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion

Mechanically ventilated participants administered placebo as a single IV infusion

Outcomes

Primary Outcome Measures

Cohort 1: Proportion of subjects 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 will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome has met a NIAID score of 2 will be considered as using mechanical ventilation. 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.
Cohort 2: Mortality rate at Day 29
Mortality rate is defined as the proportion of subjects who have died by Day 29.

Secondary Outcome Measures

Cohort 1: Mortality rate at Day 29
Mortality rate is defined as the proportion of participants who die.
Cohort 1: Ventilation-free survival by Day 29
Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.
Cohort 1: Overall survival by Day 29
Defined as time from randomization to death; subjects still alive will be censored at Day 29.
Cohort 2: Time to 1-point clinical improvement 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.

Full Information

First Posted
June 23, 2020
Last Updated
September 21, 2022
Sponsor
Kiniksa Pharmaceuticals, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04447469
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
July 27, 2020 (Actual)
Primary Completion Date
November 12, 2021 (Actual)
Study Completion Date
January 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kiniksa Pharmaceuticals, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID
Keywords
COVID-19, pneumonia, hyper-inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
815 (Actual)

8. Arms, Groups, and Interventions

Arm Title
10 mg/kg (Cohort 1)
Arm Type
Active Comparator
Arm Description
Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Arm Title
6 mg/kg (Cohort 1)
Arm Type
Active Comparator
Arm Description
Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Arm Title
Placebo (Cohort 1)
Arm Type
Placebo Comparator
Arm Description
Non-mechanically ventilated participants administered placebo as a single IV infusion
Arm Title
10 mg/kg (Cohort 2)
Arm Type
Active Comparator
Arm Description
Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Arm Title
6 mg/kg (Cohort 2)
Arm Type
Active Comparator
Arm Description
Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Arm Title
Placebo (Cohort 2)
Arm Type
Placebo Comparator
Arm Description
Mechanically ventilated participants administered placebo as a single IV infusion
Intervention Type
Drug
Intervention Name(s)
mavrilimumab
Other Intervention Name(s)
(KPL-301; CAM3001)
Intervention Description
anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
matching placebo
Primary Outcome Measure Information:
Title
Cohort 1: Proportion of subjects alive and free of mechanical ventilation at Day 29
Description
Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome has met a NIAID score of 2 will be considered as using mechanical ventilation. 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.
Time Frame
Day 29
Title
Cohort 2: Mortality rate at Day 29
Description
Mortality rate is defined as the proportion of subjects who have died by Day 29.
Time Frame
Day 29
Secondary Outcome Measure Information:
Title
Cohort 1: Mortality rate at Day 29
Description
Mortality rate is defined as the proportion of participants who die.
Time Frame
By Day 29
Title
Cohort 1: Ventilation-free survival by Day 29
Description
Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.
Time Frame
By Day 29
Title
Cohort 1: Overall survival by Day 29
Description
Defined as time from randomization to death; subjects still alive will be censored at Day 29.
Time Frame
Day 29
Title
Cohort 2: Time to 1-point clinical improvement by Day 29
Description
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.
Time Frame
By Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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. 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
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
SHARP Health Care
City
San Diego
State/Province
California
ZIP/Postal Code
92110
Country
United States
Facility Name
Affinity Health
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60644
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Allina Health System
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Mercy Clinic Hospitalists
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Bryn Mawr Hospital
City
Bryn Mawr
State/Province
Pennsylvania
ZIP/Postal Code
19010
Country
United States
Facility Name
University of Texas Health Sciences
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hospital Cardio Pulmonar
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40170-130
Country
Brazil
Facility Name
Hospital Luxemburgo - Associação Mário Penna
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30380-472
Country
Brazil
Facility Name
CPCLIN - Centro de Pesquisas Clínicas
City
Natal
State/Province
Rio Grande Do Norte
ZIP/Postal Code
59025-050
Country
Brazil
Facility Name
Hospital Bruno Born
City
Lajeado
State/Province
Rio Grande Do Sul
ZIP/Postal Code
95900-000
Country
Brazil
Facility Name
UPECLIN - Unidade de Pesquisa Clínica
City
Botucatu
State/Province
Sao Paulo
ZIP/Postal Code
18618-686
Country
Brazil
Facility Name
IPECC - Instituto de Pesquisa Clínica de Campinas
City
Campinas
State/Province
Sao Paulo
ZIP/Postal Code
13060-080
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
City
Ribeirão Preto
State/Province
São Paulo
ZIP/Postal Code
65470-000
Country
Brazil
Facility Name
Hospital Adventista de Belem
City
Belém
ZIP/Postal Code
66093-904
Country
Brazil
Facility Name
IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará
City
Fortaleza
ZIP/Postal Code
60192-340
Country
Brazil
Facility Name
Fundação Faculdade Regional de Medicina de São José do Rio Preto
City
São José
ZIP/Postal Code
15090-000
Country
Brazil
Facility Name
Hospital Alemão Oswaldo Cruz
City
São Paulo
ZIP/Postal Code
01323-020
Country
Brazil
Facility Name
Clinica Las Condes
City
Santiago
ZIP/Postal Code
7550000
Country
Chile
Facility Name
Hospital Clinico Universidad de Chile
City
Santiago
ZIP/Postal Code
8380456
Country
Chile
Facility Name
Hospital Nacional Alberto Sabogal Sologuren
City
Bellavista
ZIP/Postal Code
07011
Country
Peru
Facility Name
Essalud - Hospital de Emergencias Grau
City
Lima Cercado
ZIP/Postal Code
15082
Country
Peru
Facility Name
Hospital Nacional Cayetano Heredia
City
San Martín De Porres
ZIP/Postal Code
15102
Country
Peru
Facility Name
Clinica Providencia
City
San Miguel
ZIP/Postal Code
15088
Country
Peru
Facility Name
University of Cape Town - Lung Institute
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7700
Country
South Africa
Facility Name
IATROS International
City
Bloemfontein
ZIP/Postal Code
9301
Country
South Africa
Facility Name
Tiervlei Trial Center
City
Cape Town
ZIP/Postal Code
7530
Country
South Africa
Facility Name
TASK Eden
City
George
ZIP/Postal Code
6529
Country
South Africa
Facility Name
Into Research - Little Company of Mary Medical Center
City
Pretoria
ZIP/Postal Code
0181
Country
South Africa
Facility Name
Limpopo Clinical Research Initiative
City
Rustenburg
ZIP/Postal Code
0299
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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