NCT04414631

Conestat Alfa in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19

Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19: a Randomized, Parallel-group, Open-label, Multi-center Pilot Trial (PROTECT-COVID-19).

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to analyze if administration of conestat alfa for 72 hours in addition to standard of care (SOC) in patients hospitalized with non-critical SARS-CoV-2 pneumonia (WHO Ordinal Scale Score 3 or 4) reduces the risk of disease progression to Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).

Detailed description

Systemic hyperinflammation is a hallmark of more severe stages of COVID-19 leading to acute respiratory distress syndrome, mechanical ventilation and ultimately death. In this stage, COVID-19 is associated with a decrease in suppressor and regulatory T cell counts and an extensive release of proinflammatory cytokines and biomarkers called a cytokine storm, which is thought to be the major driver of severe pneumonia caused by SARS-CoV-2. C1 esterase inhibitor (C1INH) is a member of the serpin superfamily of serine-protease inhibitors and is a strong inhibitor of the complement System (CS) and the kinin-kallikrein (KK) System. Conestat alfa is a recombinant human C1INH, that shares an identical protein structure with plasma-derived C1INH. The rationale of the current trial is based upon the following assumptions: In the context of COVID-19, conestat alfa treatment may 1) dampen uncontrolled complement activation and collateral lung damage and 2) reduce capillary leakage and subsequent pulmonary edema by direct inhibition of KK system. The aim of this study is to analyze administration of conestat alfa for 72 hours in addition to standard of care in patients hospitalized with non-critical SARS-CoV-2 pneumonia (WHO Ordinal Scale Score 3 or 4) and its association with clinical severity on day 7 after inclusion and the risk of disease progression to Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).

Conditions

• Coronavirus Infections

Interventions

Type	Name	Description
DRUG	Conestat alfa	Conestat alfa (8400 Units (U) followed by 4200 U every 8 hours, 9 administrations in total) will be administered as a slow intravenous injection (5-10 minutes) over a 72 hour period.

Timeline

• Start date: 2020-08-06
• Primary completion: 2021-09-15
• Completion: 2021-09-15
• First posted: 2020-06-04
• Last updated: 2021-11-09

Locations

5 sites across 3 countries: Brazil, Mexico, Switzerland