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

Kiniksa Pharmaceuticals International, plc

Status and phase: Completed; Phase 3; Phase 2

Conditions: COVID

Treatments: Other: Placebo; Drug: mavrilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04447469

KPL-301-C203

Details and patient eligibility

About

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

Full 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.

Enrollment: 814 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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814 participants in 6 patient groups, including a placebo group

10 mg/kg (Cohort 1)

Active Comparator group

Description:

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

Treatment:

Drug: mavrilimumab

6 mg/kg (Cohort 1)

Active Comparator group

Description:

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

Treatment:

Drug: mavrilimumab

Placebo (Cohort 1)

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo

10 mg/kg (Cohort 2)

Active Comparator group

Description:

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

Treatment:

Drug: mavrilimumab

6 mg/kg (Cohort 2)

Active Comparator group

Description:

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

Treatment:

Drug: mavrilimumab

Placebo (Cohort 2)

Placebo Comparator group

Description:

Mechanically ventilated participants administered placebo as a single IV infusion

Treatment:

Other: Placebo