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

Sponsor

Kiniksa Pharmaceuticals, Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT04447469

Collaborator

(none)

815

Enrollment

Locations

Arms

17.6

Actual Duration (Months)

25.5

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
COVID	Drug: mavrilimumab Other: Placebo	Phase 2/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-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.

Study Design

Study Type:

Interventional

Actual Enrollment :

815 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 27, 2020

Actual Primary Completion Date :

Nov 12, 2021

Actual Study Completion Date :

Jan 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 10 mg/kg (Cohort 1) Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion	Drug: mavrilimumab anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4]) Other Names: (KPL-301; CAM3001)
Active Comparator: 6 mg/kg (Cohort 1) Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion	Drug: mavrilimumab anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4]) Other Names: (KPL-301; CAM3001)
Placebo Comparator: Placebo (Cohort 1) Non-mechanically ventilated participants administered placebo as a single IV infusion	Other: Placebo matching placebo
Active Comparator: 10 mg/kg (Cohort 2) Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion	Drug: mavrilimumab anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4]) Other Names: (KPL-301; CAM3001)
Active Comparator: 6 mg/kg (Cohort 2) Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion	Drug: mavrilimumab anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4]) Other Names: (KPL-301; CAM3001)
Placebo Comparator: Placebo (Cohort 2) Mechanically ventilated participants administered placebo as a single IV infusion	Other: Placebo matching placebo

Outcome Measures

Primary Outcome Measures

Cohort 1: Proportion of subjects alive and free of mechanical ventilation at Day 29 [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.
Cohort 2: Mortality rate at Day 29 [Day 29]
Mortality rate is defined as the proportion of subjects who have died by Day 29.

Secondary Outcome Measures

Cohort 1: Mortality rate at Day 29 [By Day 29]
Mortality rate is defined as the proportion of participants who die.
Cohort 1: Ventilation-free survival by Day 29 [By Day 29]
Defined as time from randomization to ventilation or death; subjects still alive will be censored at Day 29.
Cohort 1: Overall survival by Day 29 [Day 29]
Defined as time from randomization to death; subjects still alive will be censored at Day 29.
Cohort 2: Time to 1-point clinical improvement by Day 29 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	SHARP Health Care	San Diego	California	United States	92110
3	Affinity Health	Chicago	Illinois	United States	60644
4	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
5	Allina Health System	Minneapolis	Minnesota	United States	55407
6	Mercy Clinic Hospitalists	Springfield	Missouri	United States	65804
7	University of Cincinnati	Cincinnati	Ohio	United States	45229
8	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
9	University of Texas Health Sciences	Houston	Texas	United States	77030
10	Hospital Cardio Pulmonar	Salvador	Bahia	Brazil	40170-130
11	Hospital Luxemburgo - Associação Mário Penna	Belo Horizonte	Minas Gerais	Brazil	30380-472
12	CPCLIN - Centro de Pesquisas Clínicas	Natal	Rio Grande Do Norte	Brazil	59025-050
13	Hospital Bruno Born	Lajeado	Rio Grande Do Sul	Brazil	95900-000
14	UPECLIN - Unidade de Pesquisa Clínica	Botucatu	Sao Paulo	Brazil	18618-686
15	IPECC - Instituto de Pesquisa Clínica de Campinas	Campinas	Sao Paulo	Brazil	13060-080
16	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo	Brazil	65470-000
17	Hospital Adventista de Belem	Belém		Brazil	66093-904
18	IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará	Fortaleza		Brazil	60192-340
19	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José		Brazil	15090-000
20	Hospital Alemão Oswaldo Cruz	São Paulo		Brazil	01323-020
21	Clinica Las Condes	Santiago		Chile	7550000
22	Hospital Clinico Universidad de Chile	Santiago		Chile	8380456
23	Hospital Nacional Alberto Sabogal Sologuren	Bellavista		Peru	07011
24	Essalud - Hospital de Emergencias Grau	Lima Cercado		Peru	15082
25	Hospital Nacional Cayetano Heredia	San Martín De Porres		Peru	15102
26	Clinica Providencia	San Miguel		Peru	15088
27	University of Cape Town - Lung Institute	Cape Town	Western Cape	South Africa	7700
28	IATROS International	Bloemfontein		South Africa	9301
29	Tiervlei Trial Center	Cape Town		South Africa	7530
30	TASK Eden	George		South Africa	6529
31	Into Research - Little Company of Mary Medical Center	Pretoria		South Africa	0181
32	Limpopo Clinical Research Initiative	Rustenburg		South Africa	0299