Mavrilimumab in Severe COVID-19 Pneumonia and Hyper-inflammation (COMBAT-19)

NCT04397497 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: COMBAT-19
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.

Conditions

Covid-19; Acute Respiratory Failure; ARDS, Human; Sars-CoV2; Viral Pneumonia

Keywords

covid-19; Acute respiratory failure; mavrilimumab; GM-CSF; GM-CSF receptor alpha; SARS-CoV2; viral pneumonia

Outcome Measures

Primary Outcomes (1)

• Reduction in the dependency on oxygen supplementation

  Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm

  within day 14 of treatment

Secondary Outcomes (11)

• Proportion of responders (using the WHO 7-point ordinal scale)

  Day 7, 14, and 28

• Time to response (using the WHO 7-point ordinal scale)

  Within day 28 of intervention

• Proportion of improving patients (using the WHO 7-point ordinal scale)

  At day 7, 14, and 28

• Time to resolution of fever

  Within day 28 of intervention

• Reduction in case fatality

  Within day 28 of intervention

Other Outcomes (8)

• Clinical efficacy of mavrilimumab compared to the control arm by clinical severity

  Within day 28 of intervention

• Changes in serum IL-6 (exploratory biomarker)

  By day 84

• Changes in serum IL-1RA (exploratory biomarker)

  By day 84

Study Arms (2)

Mavrilimumab

EXPERIMENTAL

Single dose of IV Mavrilimumab

Drug: Mavrilimumab

Placebo

PLACEBO COMPARATOR

Single dose of matching IV placebo

Drug: Placebo

Interventions

Mavrilimumab DRUG

human monoclonal antibody targeting GM-CSF receptor-alpha

Also known as: KPL-301, CAM-3001

Mavrilimumab

Placebo DRUG

matching volume of diluent

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults (≥ 18 years of age)
• Signed informed consent by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative or according to local guidelines
• Patients clinically diagnosed with SARS-CoV-2 virus by PCR or by other approved diagnostic methodology
• Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray or CT scan with pulmonary infiltrates
• Patient requiring oxygen supplementation (i.e. with a SpO2 ≤ 92% while breathing room air) and having a PAO2/FIO2 ratio ≤ 300 mmHg
• Lactate dehydrogenase (LDH) \> normal range and at least one of the following:
• fever \> 38.0 °C;
• increased levels of C-reactive Protein (CRP) ≥ 10x UNL mg/L (≥ 60 mg/l);
• increased levels of ferritin ≥ 2.5x UNL ( ≥ 1000 μg/L)

You may not qualify if:

• Onset of COVID-19 pneumonia symptoms (i.e. dyspnea/respiratory insufficiency) \>14 days
• On mechanical ventilation at the time of randomization
• A PaO2/FiO2 \< 100 mmHg
• Uncontrolled systemic infection (other than COVID-19)
• Hypersensitivity to the active substance or to any of the excipients of the experimental drug
• Total neutrophil count \< 1500/mm3
• Severe hepatic cirrhosis
• History of chronic HBV or HCV infection
• Known or active tuberculosis (TB) or a history of incompletely treated TB; suspected or known extrapulmonary tuberculosis
• Moderate/severe heart failure (NYHA Class 3 or 4)
• Any prior (within the defined periods below) or concurrent use of immunosuppressive therapies including but not limited to the following:
• Anti-IL-6, anti-IL-6R antagonists or Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period;
• Cell-depleting agents (e.g., anti CD20) without evidence of recovery of B cells to baseline level;
• Anakinra within 1 week of baseline; canakinumab within 8 weeks of baseline; abatacept within 8 weeks of baseline.
• Tumor necrosis factor (TNF) inhibitors within 2-8 weeks (etanercept within 2 weeks, infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or after at least 5 half-lives have elapsed, whichever is longer;

Sponsors & Collaborators

• Ospedale San Raffaele: lead

Study Sites (3)

IRCCS Policlinico San Donato

San Donato, MI, 20097, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

IRCCS Istituto Ortopedico Galeazzi

Milan, 20161, Italy

Location

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Pneumonia, Viral

Interventions

mavrilimumab

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Lorenzo Dagna, MD

  Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Dagna, MD

CONTACT

+390226434683; dagna.lorenzo@unisr.it

Giacomo De Luca, MD

CONTACT

+390226434683; deluca.giacomo@hsr.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Unit of Immunology Rheumatology Allergy and Rare Diseases (UnIRAR)

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: May 21, 2020
• Study Start: May 22, 2020
• Primary Completion: September 22, 2020
• Study Completion: November 22, 2020
• Last Updated: May 26, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

IT (3)