Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation

Sponsor
Virginia Commonwealth University (Other)
Overall Status
Completed
CT.gov ID
NCT04463004
Collaborator
Kiniksa Pharmaceuticals, Ltd. (Industry)
2
1
2
2.9
0.7

Study Details

Study Description

Brief Summary

The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This prospective, Phase 2, multi-center, blinded randomized placebo-controlled study is designed to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe Covid-19 pneumonia and clinical and biological features of hyper-inflammation.

The study population includes patients who have severe pneumonia, defined as hospitalization due to Covid-19 with abnormal chest imaging and SpO2 <92% on room air or requirement for supplemental oxygen.

Enrollment: The study will be performed in approximately 4 months total, starting from the first patient enrolled with enrollment expected to complete within 2 months.

Follow-up period: The follow-up period is 60 days for each patient enrolled.

A total of 60 patients will be randomized using a 1:1 allocation ratio: 30 subjects will receive mavrilimumab, and 30 subjects will receive placebo infusion. The investigator, clinical team, and subject will be blinded to treatment assignment.

Participants will be identified by regular review of hospitalized COVID19 patients to evaluate for inclusion and exclusion criteria. Participants will then be approached in the standard manner by study investigator and coordinator/research nurse.

Research interventions will take place in the hospital in accordance with privacy standards.

The study team is informed on all study procedures and requirements with daily meetings and the opportunity to continuously update through secure channels.

In this multicenter consortium, each participating site will have their own IND for patients enrolled at their site. Data collection, data analysis, and randomization scheme will be performed by one site, Cleveland Clinic C5 Research.

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
Actual Study Start Date :
Sep 2, 2020
Actual Primary Completion Date :
Nov 30, 2020
Actual Study Completion Date :
Nov 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Intervention

Treatment infusion

Drug: Mavrilimumab
Treatment infusion
Other Names:
  • KPL-301
  • Placebo Comparator: Control

    Placebo infusion

    Drug: Placebos
    Placebo infusion

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Subjects Alive and Off of Oxygen at Day 14 [14 days]

      Number of subjects alive and off of oxygen

    Secondary Outcome Measures

    1. Number of Subjects Alive and Without Respiratory Failure at 28 Days [28 days]

      Number of subjects alive and without respiratory failure

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Written informed consent must be obtained before any assessment is performed

    2. Documented COVID19 pneumonia defined as positive SARS-CoV2 test AND abnormalities/ infiltrates on chest x-ray or computed tomography AND active fever or documented fever within 24-48 hours or ongoing anti-pyretic use to suppress fever

    3. Hypoxia (Room air SpO2 <92% or requirement for supplemental oxygen)

    4. Increased serum inflammatory marker (CRP > 5 mg/dL)

    5. Severity of disease warrants inpatient hospitalization

    Exclusion Criteria:
    1. Onset of COVID-19 symptoms >14 days

    2. Age < 18 years-old

    3. Hospitalized >7 days

    4. Mechanically ventilated

    5. Serious concomitant illness which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to):

    • History of immunodeficiency (congenital or acquired)

    • Neutropenia (absolute neutrophil count <1,500/mm3)

    • History of solid-organ or bone marrow transplant

    • History of current systemic autoimmune or autoinflammatory disease(s) requiring systemic immune-modulating drugs

    • History of myeloproliferative disorder or active malignancy receiving cytotoxic chemotherapy

    • Pre-existing severe pulmonary disease (i.e. steroid dependent asthma, COPD on home oxygen, or other restrictive/obstructive lung disease requiring home oxygen)

    • Pre-existing severe left ventricular systolic dysfunction (i.e. LVEF <35%)

    • Known or suspected active tuberculosis (TB), latent TB, or history of incompletely treated TB or at high risk for latent TB (from exposure or prior incarceration)

    • History of active or latent viral hepatitis (i.e. Hepatitis B or C)

    • Concomitant uncontrolled systemic bacterial or fungal infection

    • Concomitant viral infection other than COVID-19 (e.g. Influenza, other respiratory viruses)

    • History of chronic liver disease with portal hypertension

    • History of end-stage renal disease on chronic renal replacement therapy

    1. Recent treatment with cell-depleting biological therapies (e.g., anti-CD20) within 12 months, cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-Interleukin [IL]-6 receptor [e.g. 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, or mycophenolate mofetil (MMF) within 4 weeks

    2. Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks

    3. Chronic or recent corticosteroid use > 10 mg/day

    4. Pregnant. Breast-feeding women are eligible with the decision to continue or discontinue breast-feeding during therapy taking into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother

    5. Enrolled in another investigational study using immunosuppressive therapy

    6. Known hypersensitivity to mavrilimumab or any of its excipients

    7. In the opinion of the investigator, unable to comply with the requirements to participate in the study

    8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug. Such methods include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

    • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject

    • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Virginia Commonwealth University Richmond Virginia United States 23298

    Sponsors and Collaborators

    • Virginia Commonwealth University
    • Kiniksa Pharmaceuticals, Ltd.

    Investigators

    • Principal Investigator: Antonio Abbate, MD, PhD, Virginia Commonwealth University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Virginia Commonwealth University
    ClinicalTrials.gov Identifier:
    NCT04463004
    Other Study ID Numbers:
    • HM20019145
    First Posted:
    Jul 9, 2020
    Last Update Posted:
    Aug 11, 2021
    Last Verified:
    Aug 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
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Intervention Control
    Arm/Group Description Treatment infusion Mavrilimumab: Treatment infusion Placebo infusion Placebos: Placebo infusion
    Period Title: Overall Study
    STARTED 1 1
    COMPLETED 1 1
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Intervention Control Total
    Arm/Group Description Treatment infusion Mavrilimumab: Treatment infusion Placebo infusion Placebos: Placebo infusion Total of all reporting groups
    Overall Participants 1 1 2
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55
    (0)
    59
    (0)
    57
    (0)
    Sex: Female, Male (Count of Participants)
    Female
    1
    100%
    0
    0%
    1
    50%
    Male
    0
    0%
    1
    100%
    1
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    1
    100%
    1
    100%
    2
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    100%
    1
    50%
    White
    1
    100%
    0
    0%
    1
    50%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    1
    100%
    1
    100%
    2
    100%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Subjects Alive and Off of Oxygen at Day 14
    Description Number of subjects alive and off of oxygen
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Control
    Arm/Group Description Treatment infusion Mavrilimumab: Treatment infusion Placebo infusion Placebos: Placebo infusion
    Measure Participants 1 1
    Count of Participants [Participants]
    1
    100%
    1
    100%
    2. Secondary Outcome
    Title Number of Subjects Alive and Without Respiratory Failure at 28 Days
    Description Number of subjects alive and without respiratory failure
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Control
    Arm/Group Description Treatment infusion Mavrilimumab: Treatment infusion Placebo infusion Placebos: Placebo infusion
    Measure Participants 1 1
    Number [participants]
    1
    100%
    1
    100%

    Adverse Events

    Time Frame 60 days
    Adverse Event Reporting Description Daily assessment and chart review with routine labs while in patient, Virtual telehealth assessment on day 14, 21, 28 and 60.
    Arm/Group Title Intervention Control
    Arm/Group Description Treatment infusion Mavrilimumab: Treatment infusion Placebo infusion Placebos: Placebo infusion
    All Cause Mortality
    Intervention Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/1 (0%)
    Serious Adverse Events
    Intervention Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Intervention Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/1 (0%)

    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/Title Antonio Abbate, MD, PhD
    Organization Virginia Commonwealth University
    Phone 804-628-1215
    Email antonio.abbate@vcuhealth.org
    Responsible Party:
    Virginia Commonwealth University
    ClinicalTrials.gov Identifier:
    NCT04463004
    Other Study ID Numbers:
    • HM20019145
    First Posted:
    Jul 9, 2020
    Last Update Posted:
    Aug 11, 2021
    Last Verified:
    Aug 1, 2021