Clinical trial NCT04447469: Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation
Official title: A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID
Keywords: COVID-19
pneumonia
hyper-inflammation
Lead sponsor: Kiniksa Pharmaceuticals International, plc
Sponsor class: INDUSTRY
Collaborators: name: Kiniksa Pharmaceuticals, Ltd.
First posted: 2020-06-25
Enrollment: 814
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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-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.

Eligibility 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

Primary outcomes:
measure: Cohort 1, Phase 2: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
timeFrame: Day 29
measure: Cohort 1, Phase 3: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
timeFrame: Day 29
measure: Cohort 2, Phase 2: Percentage of Participants Who Died by Day 29
timeFrame: Day 29
measure: Cohort 2, Phase 3: Percentage of Participants Who Died by Day 29
timeFrame: Day 29
Secondary outcomes:
measure: Cohort 1, Phase 2: Time to 2-point Clinical Improvement by Day 29
timeFrame: Day 29
measure: Phase 2, Cohort 1: Time to Return to Room Air or Discharge by Day 29
timeFrame: Day 29
measure: Phase 2, Cohort 1: Percentage of Participants Who Die by Day 29
timeFrame: Day 29
measure: Phase 2, Cohort 2: Time to 1-Point Clinical Improvement by Day 29
timeFrame: Day 29
measure: Phase 3, Cohort 1: Percentage of Participants Who Died at Day 29
timeFrame: Day 29
measure: Phase 3, Cohort 1: Ventilation-Free Survival (Time to Ventilation or Death) by Day 29
timeFrame: Day 29
measure: Phase 3, Cohort 1: Overall Survival by Day 29
timeFrame: Day 29
measure: Phase 3, Cohort 2: Time to 1-point Clinical Improvement by Day 29
timeFrame: Day 29
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Diego
country: United States
facility: SHARP Health Care
state: California
city: Chicago
country: United States
facility: Affinity Health
state: Illinois
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Minneapolis
country: United States
facility: Allina Health System
state: Minnesota
city: Springfield
country: United States
facility: Mercy Clinic Hospitalists
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Sciences
state: Texas
city: Salvador
country: Brazil
facility: Hospital Cardio Pulmonar
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Hospital Luxemburgo - Associação Mário Penna
state: Minas Gerais
city: Natal
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas
state: Rio Grande Do Norte
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
state: Rio Grande Do Sul
city: Botucatu
country: Brazil
facility: UPECLIN - Unidade de Pesquisa Clínica
state: Sao Paulo
city: Campinas
country: Brazil
facility: IPECC - Instituto de Pesquisa Clínica de Campinas
state: Sao Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: São Paulo
city: Belém
country: Brazil
facility: Hospital Adventista de Belem
city: Fortaleza
country: Brazil
facility: IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará
city: São José
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
city: Santiago
country: Chile
facility: Clinica Las Condes
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Chile
city: Bellavista
country: Peru
facility: Hospital Nacional Alberto Sabogal Sologuren
city: Lima Cercado
country: Peru
facility: Essalud - Hospital de Emergencias Grau
city: San Martín De Porres
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: San Miguel
country: Peru
facility: Clinica Providencia
city: Cape Town
country: South Africa
facility: University of Cape Town - Lung Institute
state: Western Cape
city: Bloemfontein
country: South Africa
facility: IATROS International
city: Cape Town
country: South Africa
facility: Tiervlei Trial Center
city: George
country: South Africa
facility: TASK Eden
city: Pretoria
country: South Africa
facility: Into Research - Little Company of Mary Medical Center
city: Rustenburg
country: South Africa
facility: Limpopo Clinical Research Initiative
Study officials:
References: