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

University Hospital Basel

Status and phase

Terminated

Phase 2

Conditions

Coronavirus Infections

Treatments

Drug: Conestat alfa

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04414631

2020-01252 me20Osthoff3;

Details and patient eligibility

About

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).

Full 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).

Enrollment

80 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Informed Consent as documented by signature
admitted to the hospital because of confirmed (by a positive SARS-CoV-2 PCR result) COVID-19 infection
evidence of pulmonary involvement on CT scan or X-ray of the chest (e.g. ground glass opacities)
symptom onset within the previous 10 days OR shortness of breath within the previous 5 days. Symptoms include fever or one respiratory symptom (patients presenting later may have already progressed to an inflammatory state that is potentially not amenable to C1INH treatment). Respiratory symptoms include cough, sore throat, hemoptysis, shortness of breath, runny nose, or chest pain.
expected to remain an inpatient over the next three calender days from time of enrolment
at least one additional risk factor for progression to mechanical ventilation: 1) arterial hypertension, 2) >50 years, 3) obesity (BMI>30.0 kg/m2), 4) cardiovascular disease, 5) chronic pulmonary disease, 7) chronic renal disease, 6) C-reactive protein of >35mg/L, 7) oxygen saturation at rest in ambient air of <94%. Cardiovascular disease includes a history of coronary artery disease, cerebrovascular disease, peripheral artery disease, rheumatic heart disease, congenital heart disease and of recent (< 3 months) deep vein thrombosis or pulmonary embolism. Chronic pulmonary disease includes a history of chronic obstructive pulmonary disease, asthma, occupational lung disease, interstitial lung disease or of pulmonary hypertension. Chronic renal disease is defined as a history of an estimated glomerular filtration rate (according to the Chronic Kidney Disease Epidemiology Collaboration equation) < 60ml/min/1.73 m2 for at least three months.

Exclusion criteria

Contraindications to the class of drugs under study (C1 esterase inhibitor), e.g. known hypersensitivity or allergy to class of drugs or the investigational product
Treatment with tocilizumab or another Il-6R or Il-6 inhibitor before enrolment
History or suspicion of allergy to rabbits
Women who are pregnant or breast feeding
Active or planned treatment with any other complement inhibitor
Liver cirrhosis (any Child-Pugh score)
Incapacity or inability to provide informed consent
Currently admitted to an ICU or expected admission within the next 24 hours
Currently receiving invasive or non-invasive ventilation (with the exception of high-flow oxygen therapy).
In the opinion of the treating time, death is deemed to be imminent and inevitable within the next 24 hours
Participation in another study with investigational drug within the 30 days preceding and during the present study with the following exemptions: 1) participation in COVID-19 drug trials started at least 48 hours before admission (e.g. postexposure prophylaxis with hydroxychloroquine) and 2) participation in COVID-19 drug trials during ICU admission
Previous enrolment into the current study
Enrolment of the investigator, his/her family members, employees and other dependent persons
Any uncontrolled or significant concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements