Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation
Purpose
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
Condition
- COVID
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
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
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator 10 mg/kg (Cohort 1) |
Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion |
|
|
Active Comparator 6 mg/kg (Cohort 1) |
Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion |
|
|
Placebo Comparator Placebo (Cohort 1) |
Non-mechanically ventilated participants administered placebo as a single IV infusion |
|
|
Active Comparator 10 mg/kg (Cohort 2) |
Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion |
|
|
Active Comparator 6 mg/kg (Cohort 2) |
Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion |
|
|
Placebo Comparator Placebo (Cohort 2) |
Mechanically ventilated participants administered placebo as a single IV infusion |
|
More Details
- Status
- Completed
- Sponsor
- Kiniksa Pharmaceuticals, Ltd.
Study Contact
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.