NCT04397497

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

A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Ospedale San Raffaele · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

To evaluate the efficacy and safety of mavrilimumab versus placebo in addition to best standard of care (SoC) in the treatment of COVID-19 pneumonia. As of May 13, 2020, COVID-19 has been confirmed in more than 4.2 million people worldwide. Mortality rate has been reported to be approximately 3.7%, which is nearly 4 times higher than that of influenza: there is an urgent need for effective treatment. Accumulating evidence suggests that patients with severe acute COVID-19 pneumonia have a cytokine storm syndrome, or unbalanced hyper-inflammatory response resulting in markedly elevated cytokine and chemokine production. GM-CSF is a cytokine with dual roles as a critical pulmonary hormone and proinflammatory properties that can exaggerate tissue inflammation. Recent preliminary uncontrolled clinical observations on 13 non-mechanically-ventilated patients in the promoter institution suggest that GM-CSF pathway blockade with mavrilimumab is an effective and well-tolerated treatment for COVID-19 pneumonia. We will perform 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 non-mechanically-ventilated adult patients to mavrilimumab or placebo, in addition to standard of care per local practice, which may include but not limited to anti-viral treatment, hydroxychloroquine, low-dose corticosteroids (≤ 10 mg of prednisone or equivalent) and/or supportive care. The total trial duration will be 12 weeks after single mavrilimumab or placebo infusion. Safety will be closely monitored by a dedicated external data safety monitoring board (DSMB) at regular intervals during the study.

Conditions

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

Interventions

Type	Name	Description
DRUG	Mavrilimumab	human monoclonal antibody targeting GM-CSF receptor-alpha
DRUG	Placebo	matching volume of diluent

Timeline

• Start date: 2020-05-22
• Primary completion: 2020-09-22
• Completion: 2020-11-22
• First posted: 2020-05-21
• Last updated: 2020-05-26

Locations

3 sites across 1 country: Italy

Regulatory

• FDA-regulated drug study