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

NCT04447469 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KPL-301-C203
• Study Type: interventional
• Target: 814
• Locations: 5 countries
• Sites: 32

Brief Summary

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

Conditions

COVID

Keywords

COVID-19; pneumonia; hyper-inflammation

Outcome Measures

Primary Outcomes (4)

• Cohort 1, Phase 2: Percentage of Participants 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 was evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Participants whose clinical outcome met a NIAID score of 2 were considered as using mechanical ventilation. The NIAID score 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

• Cohort 1, Phase 3: Percentage of Participants 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 was evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Participants whose clinical outcome met a NIAID score of 2 were considered as using mechanical ventilation. The NIAID score 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

• Cohort 2, Phase 2: Percentage of Participants Who Died by Day 29

  Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.

  Day 29

• Cohort 2, Phase 3: Percentage of Participants Who Died by Day 29

  Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.

  Day 29

Secondary Outcomes (8)

• Cohort 1, Phase 2: Time to 2-point Clinical Improvement by Day 29

  Day 29

• Phase 2, Cohort 1: Time to Return to Room Air or Discharge by Day 29

  Day 29

• Phase 2, Cohort 1: Percentage of Participants Who Die by Day 29

  Day 29

• Phase 2, Cohort 2: Time to 1-Point Clinical Improvement by Day 29

  Day 29

• Phase 3, Cohort 1: Percentage of Participants Who Died at Day 29

  Day 29

Study Arms (6)

10 mg/kg (Cohort 1)

ACTIVE COMPARATOR

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

Drug: mavrilimumab

6 mg/kg (Cohort 1)

ACTIVE COMPARATOR

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

Drug: mavrilimumab

Placebo (Cohort 1)

PLACEBO COMPARATOR

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

Other: Placebo

10 mg/kg (Cohort 2)

ACTIVE COMPARATOR

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

Drug: mavrilimumab

6 mg/kg (Cohort 2)

ACTIVE COMPARATOR

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

Drug: mavrilimumab

Placebo (Cohort 2)

PLACEBO COMPARATOR

Mechanically ventilated participants administered placebo as a single IV infusion

Other: Placebo

Interventions

mavrilimumab DRUG

anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G \[IgG4\])

Also known as: KPL-301, CAM3001

10 mg/kg (Cohort 1); 10 mg/kg (Cohort 2); 6 mg/kg (Cohort 1); 6 mg/kg (Cohort 2)

Placebo OTHER

matching placebo

Placebo (Cohort 1); Placebo (Cohort 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Kiniksa Pharmaceuticals International, plc: lead
• Kiniksa Pharmaceuticals, Ltd.: collaborator

Study Sites (32)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

SHARP Health Care

San Diego, California, 92110, United States

Location

Affinity Health

Chicago, Illinois, 60644, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Allina Health System

Minneapolis, Minnesota, 55407, United States

Location

Mercy Clinic Hospitalists

Springfield, Missouri, 65804, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45229, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

University of Texas Health Sciences

Houston, Texas, 77030, United States

Location

Hospital Cardio Pulmonar

Salvador, Estado de Bahia, 40170-130, Brazil

Location

Hospital Luxemburgo - Associação Mário Penna

Belo Horizonte, Minas Gerais, 30380-472, Brazil

Location

CPCLIN - Centro de Pesquisas Clínicas

Natal, Rio Grande do Norte, 59025-050, Brazil

Location

Hospital Bruno Born

Lajeado, Rio Grande do Sul, 95900-000, Brazil

Location

UPECLIN - Unidade de Pesquisa Clínica

Botucatu, São Paulo, 18618-686, Brazil

Location

IPECC - Instituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, 13060-080, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, 65470-000, Brazil

Location

Hospital Adventista de Belem

Belém, 66093-904, Brazil

Location

IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará

Fortaleza, 60192-340, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José, 15090-000, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, 01323-020, Brazil

Location

Clinica Las Condes

Santiago, 7550000, Chile

Location

Hospital Clinico Universidad de Chile

Santiago, 8380456, Chile

Location

Hospital Nacional Alberto Sabogal Sologuren

Bellavista, 07011, Peru

Location

Essalud - Hospital de Emergencias Grau

Lima Cercado, 15082, Peru

Location

Hospital Nacional Cayetano Heredia

San Martín de Porres, 15102, Peru

Location

Clinica Providencia

San Miguel, 15088, Peru

Location

University of Cape Town - Lung Institute

Cape Town, Western Cape, 7700, South Africa

Location

IATROS International

Bloemfontein, 9301, South Africa

Location

Tiervlei Trial Center

Cape Town, 7530, South Africa

Location

TASK Eden

George, 6529, South Africa

Location

Into Research - Little Company of Mary Medical Center

Pretoria, 0181, South Africa

Location

Limpopo Clinical Research Initiative

Rustenburg, 0299, South Africa

Location

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

mavrilimumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Operations Study Director
• Organization: Kiniksa Pharmaceuticals, Ltd.

studyinfo@kiniksa.com

1-781-431-9100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 25, 2020
• Study Start: July 28, 2020
• Primary Completion: November 12, 2021
• Study Completion: January 14, 2022
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD requests will be accepted after publication of the primary data manuscript
• Access Criteria: IPD access will be provided to qualified academic researchers pending the Sponsor's review of the proposed research, including scientific novelty, review of the analytical and publication plans, funding source of the proposed research, any potential conflicts of interest, and institutional capabilities to perform the planned research.

Locations

US (9); PE (4); BR (11); CL (2); ZA (6)