A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).

Sponsor
Tufts Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT04425538
Collaborator
National Institutes of Health (NIH) (NIH)
17
Enrollment
1
Location
1
Arm
7.7
Actual Duration (Months)
2.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.

Infliximab and Infliximab-abda are TNFα inhibitors currently FDA-approved for the treatment of autoimmune disorders, including Crohn's disease and rheumatoid arthritis. The risks and adverse reactions are described in the approved prescribing information for infliximab (or infliximab-abda). Infliximab will be used when available. Should infliximab be unavailable in the pharmacy, infliximab-abda, a biosimilar, will be used.

Treatment with infliximab or infliximab-abda 5mg/kg IV should ideally be administered within 6 hours of enrollment, and no more than 24 hours following enrollment. Pre-medication with Tylenol 650 mg once 30 minutes prior to infusion would be recommended. Other pre-medications may be given at the discretion of the treating physician. These include diphenhydramine 50mg by mouth, as well as prednisone 20mg by mouth, both given 30 minutes prior to infusion. Pulse and blood pressure should be monitored every 30 minutes during the infusion, and patients should be monitored for at least 30 minutes following the infusion.

Retreatment with infliximab is permitted at treating physician discretion 7-21 days following primary therapy and based on initial response; the usual treatment schedule is every 2 weeks, this interval is not strictly enforced given the uncertainty of outcomes with primary therapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
Actual Study Start Date :
Jun 1, 2020
Actual Primary Completion Date :
Jan 22, 2021
Actual Study Completion Date :
Jan 22, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Infliximab

All patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator.

Drug: Infliximab
Either infliximab or infliximab-abda will be used at the discretion of the investigator
Other Names:
  • infliximab-abda
  • Outcome Measures

    Primary Outcome Measures

    1. Time to Improvement in Oxygenation [28 Days]

      Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

    2. Incidence of Improvement in Oxygenation [28 Days]

      Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

    Secondary Outcome Measures

    1. 28-Day Survival Status [28 Days]

      Number of patients who were confirmed to be alive 28 days from enrollment onto the study.

    2. Duration of Supplemental Oxygen Administration by Nasal Cannula [28 Days]

      Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device

    3. Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula [28 Days]

      Duration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula

    4. Incidence of Mechanical Ventilation [28 Days]

      Number of patients enrolled who required mechanical ventilation

    5. Incidence of Vasopressor Support [28 Days]

      Number of participants who required vasopressor support

    6. Incidence of Extracorporeal Membrane Oxygenation [28 Days]

      Number of patients requiring extracorporeal membrane oxygenation

    7. Incidence of Fever [28 Days]

      Number of patients who exhibited fever during the study period

    8. Correlation of Cytokine Profile to Clinical Outcomes Specified in Primary and Secondary Objectives [28 Days]

      Correlation of cytokine profile to clinical outcomes specified in primary and secondary objectives

    9. Duration of Hospitalization [28 Days]

      Duration of hospitalization

    10. Incidence of Secondary Infections [28 Days]

      Number of patients who developed secondary infections

    11. Incidence of Supplemental Oxygen Administration by Nasal Cannula [28 Days]

      Incidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device

    12. Duration of Mechanical Ventilation [28 Days]

      duration of use of mechanical ventilation (for patients requiring mechanical ventilation)

    13. Incidence of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula [28 Days]

      Number of participants who required non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula

    14. Assessment of Cytokine and Inflammatory Profile at Baseline and at 48 Hours After Therapy [48 hours]

      Assessment of cytokine and inflammatory profile at baseline and at 48 hours (TNFα, IL-1b, IL-2, sIL-2r, IL-6, ferritin, ESR, CRP, CPK, troponin) after therapy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Age 18 years or older

    2. Able to provide informed consent

    3. Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan

    4. Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending

    5. And at least one of the following:

    6. Respiratory frequency ≥30/min

    7. Blood oxygen saturation ≤93% on RA

    8. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <300

    9. Worsening of lung involvement, defined as an increase in number and/or extension of pulmonary areas of consolidation, need for increased FiO2 to maintain stable O2 saturation, or worsening O2 saturation of >3% with stable FiO2

    Exclusion Criteria:
    1. Treatment with any TNFα inhibitor in the past 30 days

    2. Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation

    3. Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1000 mm3, hemoglobin <8.0g/L, platelets <50,000 per mm3, or AST or ALT greater than 5 x ULN

    4. Known active or latent Hepatitis B

    5. Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.

    6. Pregnancy

    7. Intubated for >48hours

    8. Patients with uncontrolled systemic bacterial or fungal infections (Patients with a history of positive bacterial or fungal cultures but on enrollment are on appropriate therapy with negative repeat cultures may be enrolled)

    9. Serious co-morbidity, including:

    10. Myocardial infarction (within last month)

    11. Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV)

    12. Acute stroke (within last month)

    13. Uncontrolled malignancy

    14. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2) at baseline

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Tufts Medical CenterBostonMassachusettsUnited States02111

    Sponsors and Collaborators

    • Tufts Medical Center
    • National Institutes of Health (NIH)

    Investigators

    • Principal Investigator: Paul Mathew, MD, Tufts Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Tufts Medical Center
    ClinicalTrials.gov Identifier:
    NCT04425538
    Other Study ID Numbers:
    • STUDY00000564
    First Posted:
    Jun 11, 2020
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Tufts Medical Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Period Title: Overall Study
    STARTED17
    COMPLETED17
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Overall Participants17
    Age, Customized (Count of Participants)
    18-40 years
    1
    5.9%
    41-60 years
    7
    41.2%
    >60 years
    9
    52.9%
    Sex: Female, Male (Count of Participants)
    Female
    4
    23.5%
    Male
    13
    76.5%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    4
    23.5%
    Black/African American
    2
    11.8%
    Chinese
    3
    17.6%
    Other Asian
    2
    11.8%
    Hispanic/Latino
    4
    23.5%
    Other
    1
    5.9%
    Unknown
    1
    5.9%
    Region of Enrollment (participants) [Number]
    United States
    17
    100%

    Outcome Measures

    1. Primary Outcome
    TitleTime to Improvement in Oxygenation
    DescriptionTime to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    15 patients met this endpoint whereby duration data could be obtained
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants15
    Median (Full Range) [Days]
    4
    2. Primary Outcome
    TitleIncidence of Improvement in Oxygenation
    DescriptionNumber of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    15
    88.2%
    3. Secondary Outcome
    Title28-Day Survival Status
    DescriptionNumber of patients who were confirmed to be alive 28 days from enrollment onto the study.
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    15
    88.2%
    4. Secondary Outcome
    TitleDuration of Supplemental Oxygen Administration by Nasal Cannula
    DescriptionDuration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Median (Full Range) [Days]
    3
    5. Secondary Outcome
    TitleDuration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
    DescriptionDuration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Median (Full Range) [Days]
    2.5
    6. Secondary Outcome
    TitleIncidence of Mechanical Ventilation
    DescriptionNumber of patients enrolled who required mechanical ventilation
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    7
    41.2%
    7. Secondary Outcome
    TitleIncidence of Vasopressor Support
    DescriptionNumber of participants who required vasopressor support
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    3
    17.6%
    8. Secondary Outcome
    TitleIncidence of Extracorporeal Membrane Oxygenation
    DescriptionNumber of patients requiring extracorporeal membrane oxygenation
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    1
    5.9%
    9. Secondary Outcome
    TitleIncidence of Fever
    DescriptionNumber of patients who exhibited fever during the study period
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    12
    70.6%
    10. Secondary Outcome
    TitleCorrelation of Cytokine Profile to Clinical Outcomes Specified in Primary and Secondary Objectives
    DescriptionCorrelation of cytokine profile to clinical outcomes specified in primary and secondary objectives
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    TitleDuration of Hospitalization
    DescriptionDuration of hospitalization
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Median (Full Range) [days]
    8
    12. Secondary Outcome
    TitleIncidence of Secondary Infections
    DescriptionNumber of patients who developed secondary infections
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    7
    41.2%
    13. Secondary Outcome
    TitleIncidence of Supplemental Oxygen Administration by Nasal Cannula
    DescriptionIncidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    14
    82.4%
    14. Secondary Outcome
    TitleDuration of Mechanical Ventilation
    Descriptionduration of use of mechanical ventilation (for patients requiring mechanical ventilation)
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    7 of 17 enrolled patients required mechanical ventilation
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants7
    Median (Full Range) [days]
    10
    15. Secondary Outcome
    TitleIncidence of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
    DescriptionNumber of participants who required non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
    Time Frame28 Days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    Measure Participants17
    Count of Participants [Participants]
    8
    47.1%
    16. Secondary Outcome
    TitleAssessment of Cytokine and Inflammatory Profile at Baseline and at 48 Hours After Therapy
    DescriptionAssessment of cytokine and inflammatory profile at baseline and at 48 hours (TNFα, IL-1b, IL-2, sIL-2r, IL-6, ferritin, ESR, CRP, CPK, troponin) after therapy
    Time Frame48 hours

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameAdverse events and serious adverse events were collected for each patient beginning at the time of first infliximab dose through 28 days following the last dose of infliximab. Study-wide, adverse event collection was conducted for approximately 8 months.
    Adverse Event Reporting Description Serious adverse events and all-cause mortality were collected according to clinicaltrials.gov definitions. For other adverse events, only adverse events of special interest were collected for the purposes of this trial. Adverse events of special interest include infusion reactions from infliximab treatment, anaphylaxis, and any other event deemed by the investigator to be directly related to infliximab treatment.
    Arm/Group TitleInfliximab
    Arm/Group DescriptionAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Infliximab: Either infliximab or infliximab-abda will be used at the discretion of the investigator
    All Cause Mortality
    Infliximab
    Affected / at Risk (%)# Events
    Total2/17 (11.8%)
    Serious Adverse Events
    Infliximab
    Affected / at Risk (%)# Events
    Total2/17 (11.8%)
    Cardiac disorders
    Cardiac Arrest1/17 (5.9%) 1
    Infections and infestations
    Covid-Associated Pulmonary Aspergillosis1/17 (5.9%) 1
    Other (Not Including Serious) Adverse Events
    Infliximab
    Affected / at Risk (%)# Events
    Total16/17 (94.1%)
    Cardiac disorders
    Atrial Fibrillation1/17 (5.9%)
    Intermittent Sinus Bradycardia1/17 (5.9%)
    General disorders
    Acute Infusion Reaction2/17 (11.8%)
    Infections and infestations
    Lung Infection8/17 (47.1%)
    Herpes Simplex Reactivation2/17 (11.8%)
    Investigations
    AST Elevation9/17 (52.9%)
    ALT Elevation8/17 (47.1%)
    Hyperglycemia1/17 (5.9%)
    Renal and urinary disorders
    Acute Kidney Injury3/17 (17.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDirector of Clinical Trials
    OrganizationNeely Center for Clinical Research, Tufts Medical Center
    Phone617-636-5000 ext 3264
    Emailncccr@tuftsmedicalcenter.org
    Responsible Party:
    Tufts Medical Center
    ClinicalTrials.gov Identifier:
    NCT04425538
    Other Study ID Numbers:
    • STUDY00000564
    First Posted:
    Jun 11, 2020
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021