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

Trial Profile

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

Status: Completed
Phase of Trial: Phase II

Latest Information Update: 20 May 2021

At a glance

  • Drugs Mavrilimumab (Primary)
  • Indications COVID-19 pneumonia; Inflammation; Respiratory insufficiency
  • Focus Therapeutic Use
  • Most Recent Events

    • 06 May 2021 Status changed from active, no longer recruiting to completed.
    • 22 Dec 2020 According to a Kiniksa Pharmaceuticals media release, this study is also conducted at University of Cincinnati and Virginia Commonwealth University.
    • 22 Dec 2020 According to a Kiniksa Pharmaceuticals media release, the company has closed the enrollment in this study early, as the company can focus on the registrational development program in the same patient population.

Trial Overview

Purpose

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.

Many patients in this placebo-controlled study had already been treated with remdesivir and/or corticosteroids. Patients were randomized 1:1 to a single intravenous (IV) infusion of mavrilimumab 6mg/kg (n=21) or placebo (n=19) and were followed for at least 60 days.

Primary Endpoints

Subjects Alive and Off of Oxygen at Day 14

description: Number and percentage of subjects alive and off of oxygen at day 14
time_frame: Day 14

Other Endpoints

Number of Subjects Alive and Without Respiratory Failure at Day 28

description: Number and percentage of subjects that are alive and without respiratory failure at Day 28 time_frame: Day 28

Mortality at Day 28

description: Number and percentage of patients that expired by Day 28 time_frame: Day 28 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 pneumonia treatment severe
Inflammation treatment -
Respiratory insufficiency prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 60

    Actual: 40

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Inclusion Criteria (must meet all): 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

Patient 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 6. 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 7. Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks 8. Chronic or recent corticosteroid use > 10 mg/day 9. 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 10. Enrolled in another investigational study using immunosuppressive therapy 11. Known hypersensitivity to mavrilimumab or any of its excipients 12. In the opinion of the investigator, unable to comply with the requirements to participate in the study 13. 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

Trial Details

Identifiers

Identifier Owner
NCT04399980 ClinicalTrials.gov: US National Institutes of Health
IND149324 -
IRB20-523 -

Organisations

  • Affiliations Kiniksa Pharmaceuticals

Trial Dates

  • Initiation Dates

    Actual : 20 May 2020

  • Primary Completion Dates

    Planned : 31 May 2021

    Actual : 23 Apr 2021

  • End Dates

    Planned : 31 May 2021

    Actual : 23 Apr 2021

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location USA
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
MavrilimumabPrimary Drug Intravenous Infusion

Intervention ( 6mg/kg )

Treatment infusion
Drug: Mavrilimumab (Treatment infusion) Other Name: KPL-301

Control

Placebo infusion
Drug: Placebos (Placebo infusion) Other Name: Control

Results

Therapeutic efficacy

Results from a phase II trial in patients with severe COVID-2019 pneumonia and hyper-inflammation, treatment of mavrilimumab showed an early signal of efficacy, with trends toward clinical improvement as well as lower mortality and shorter duration of mechanical ventilation in patients treated with mavrilimumab on top of corticosteroids, including dexamethasone, and/or remdesivir. A 20.5% relative increase in the primary efficacy endpoint, the proportion of patients alive and off supplemental oxygen at Day 14 (mavrilimumab: 57.1% [n=21]; placebo: 47.4% [n=19]; nominal p=0.536) was reported. There was a 20.7% relative increase in the secondary efficacy endpoint, the proportion of patients alive and without respiratory failure at Day 28 (mavrilimumab: 95.2%; placebo: 78.9%; nominal p=0.172). The percentage of patients who progressed to mechanical ventilation was similar between treatment arms (mavrilimumab: 23.8% [n=5]; placebo: 21.1% [n=4]), the median (interquartile) duration of mechanical ventilation was shorter in the mavrilimumab arm (12 [9.0, 18.0] days) compared to the placebo arm (17 [11.0, 24.5] days). Moreover, four of the five patients who progressed to mechanical ventilation in the mavrilimumab arm had recovered by Day 28, whereas all patients in the placebo arm who progressed to mechanical ventilation had died by Day 28 [2] .

Adverse events

In a phase II trial of mavrilimumab in patients with severe COVID-2019 pneumonia and hyper-inflammation, no difference in serious adverse events between the mavrilimumab arm and the placebo arm reported. One death (4.8%) in the mavrilimumab arm by day 28, compared to three deaths (15.8%) in the placebo arm (nominal p=0.222) was reported. By day 60 there was one death (4.8%) in the mavrilimumab arm, compared to four deaths (21.1%) in the placebo arm (nominal p=0.108) was reported [2] .

Publications

  1. Kiniksa Pharmaceuticals. Kiniksa Announces Data from U.S. Investigator-Initiated Study of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release

Authors

Author Total Publications First Author Last Author
Kiniksa Pharmaceuticals 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Alice Goyanes, M. D. Cleveland Clinic Health System USA
Calvin Sheng, M. D. Cleveland Clinic Health System USA
Debases Sahoo, M.D. Cleveland Clinic Health System USA
Narendrakumar Alappan, M. D. Cleveland Clinic Health System USA
Ossama K Abou Hassan, M. D. Cleveland Clinic Health System USA
Paul C Cremer, M. D.
216-445-6765
cremerp@ccf.org
216-444-6765
show details
Cleveland Clinic Health System, The Cleveland Clinic USA
Prabalini Rajendram, M. D. Cleveland Clinic Health System USA
Ravi Sunderkrishnan, M. D. Cleveland Clinic Health System USA
Robier Aguillon-Prada, M. D. Cleveland Clinic Health System USA
Shiddharth P Dugar, M. D. Cleveland Clinic Health System USA
Tom Wang, M. D. Cleveland Clinic Health System USA
Venu Menon, M. D. Cleveland Clinic Health System USA
Yuki Kuramochi, BSN, RN
216-445-4063
kuramoy@ccf.org
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Cleveland Clinic Health System Cleveland, Ohio USA
Kiniksa Pharmaceuticals, Ltd.
-
-
The Cleveland Clinic
-
-

Trial History

Event Date Event Type Comment
20 May 2021 Other trial event Last checked against Clinicaltrials.gov record. Updated 20 May 2021
06 May 2021 Status change - completed Status changed from active, no longer recruiting to completed. Updated 20 May 2021
22 Dec 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, this study is also conducted at University of Cincinnati and Virginia Commonwealth University. Updated 31 Dec 2020
22 Dec 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company has closed the enrollment in this study early, as the company can focus on the registrational development program in the same patient population. Updated 31 Dec 2020
22 Dec 2020 Results Results presented in a Kiniksa Pharmaceuticals media release. Updated 31 Dec 2020
03 Oct 2020 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 07 Oct 2020
24 May 2020 Status change - recruiting Status changed from planning to recruiting. Updated 28 May 2020
24 May 2020 Other trial event New source identified and integrated (ClinicalTrials.gov: US National Institutes of Health: NCT04399980). Updated 28 May 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020
31 Mar 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, a consortium of U.S. academic sites plans to initiate prospective, interventional studies with mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation. Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2021;.

    Available from: URL: http://clinicaltrials.gov
  2. Kiniksa Pharmaceuticals. Kiniksa Announces Data from U.S. Investigator-Initiated Study of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release
  3. Kiniksa Pharmaceuticals. Kiniksa Announces Early Evidence of Treatment Response with Mavrilimumab in 6 Patients with Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release
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