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

COVID Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04447469
• Other study ID #: KPL-301-C203
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 27, 2020
• Est. completion date: January 14, 2022

Study information

• Verified date: September 2022
• Source: Kiniksa Pharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 815
• Est. completion date: January 14, 2022
• Est. primary completion date: November 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID
• COVID-19
• Inflammation
• Pneumonia

Intervention

Drug:
• mavrilimumab
anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Ra) monoclonal antibody (human isoform immunoglobulin G [IgG4])

Other:
• Placebo
matching placebo

Locations

Country	Name	City	State
Brazil	Hospital Adventista de Belem	Belém
Brazil	Hospital Luxemburgo - Associação Mário Penna	Belo Horizonte	Minas Gerais
Brazil	UPECLIN - Unidade de Pesquisa Clínica	Botucatu	Sao Paulo
Brazil	IPECC - Instituto de Pesquisa Clínica de Campinas	Campinas	Sao Paulo
Brazil	IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará	Fortaleza
Brazil	Hospital Bruno Born	Lajeado	Rio Grande Do Sul
Brazil	CPCLIN - Centro de Pesquisas Clínicas	Natal	Rio Grande Do Norte
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo
Brazil	Hospital Cardio Pulmonar	Salvador	Bahia
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Chile	Clinica Las Condes	Santiago
Chile	Hospital Clinico Universidad de Chile	Santiago
Peru	Hospital Nacional Alberto Sabogal Sologuren	Bellavista
Peru	Essalud - Hospital de Emergencias Grau	Lima Cercado
Peru	Hospital Nacional Cayetano Heredia	San Martín De Porres
Peru	Clinica Providencia	San Miguel
South Africa	IATROS International	Bloemfontein
South Africa	Tiervlei Trial Center	Cape Town
South Africa	University of Cape Town - Lung Institute	Cape Town	Western Cape
South Africa	TASK Eden	George
South Africa	Into Research - Little Company of Mary Medical Center	Pretoria
South Africa	Limpopo Clinical Research Initiative	Rustenburg
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Affinity Health	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Health Sciences	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	Allina Health System	Minneapolis	Minnesota
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	SHARP Health Care	San Diego	California
United States	Mercy Clinic Hospitalists	Springfield	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Kiniksa Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Brazil,  Chile,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: Proportion of subjects alive and free of mechanical ventilation at Day 29	Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome has met a NIAID score of 2 will be considered as using mechanical ventilation.; The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.	Day 29
Primary	Cohort 2: Mortality rate at Day 29	Mortality rate is defined as the proportion of subjects who have died by Day 29.	Day 29
Secondary	Cohort 1: Mortality rate at Day 29	Mortality rate is defined as the proportion of participants who die.	By Day 29
Secondary	Cohort 1: Ventilation-free survival by Day 29	Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.	By Day 29
Secondary	Cohort 1: Overall survival by Day 29	Defined as time from randomization to death; subjects still alive will be censored at Day 29.	Day 29
Secondary	Cohort 2: Time to 1-point clinical improvement by Day 29	Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 29 will be censored at Day 30.	By Day 29