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

NCT04414631 | Terminated Phase 2 DMC

• 1 other identifier: 2020-01252; me20Osthoff3
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 5

Brief 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).

Conditions

Coronavirus Infections

Keywords

Systemic hyperinflammation; cytokine storm; complement system; kinin-kallikrein system; C1 esterase inhibitor; Conestat alfa; Coronavirus Disease 19 (COVID-19); Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Outcome Measures

Primary Outcomes (1)

• Disease severity

  Disease severity on the 7-point Ordinal World Health Organization (WHO) scale (for the current study, score 0 will be omitted and score 6 and 7 will be combined). The ordinal scale measures illness severity over time. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19.

  on day 7

Secondary Outcomes (3)

• Time to clinical improvement

  within 14 days after enrolment

• Proportion of participants alive and not having required invasive or non-invasive ventilation

  at 14 days after enrolment

• Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of <300mmHg)

  within 14 days after enrolment

Other Outcomes (20)

• Changes in the ordinal WHO scale

  from baseline over 14 days

• Length of hospital stay in survivors

  until day 28

• Proportion of participants progressing to mechanical ventilation

  on day 7 and day 14

Study Arms (2)

active treatment arm

ACTIVE COMPARATOR

treatment with conestat alfa in addition to standarf of care

Drug: Conestat alfa

Standard of care treatment arm

NO INTERVENTION

Standard of care treatment established at the centers

Interventions

Conestat alfa DRUG

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.

active treatment arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Pharming Technologies B.V.: collaborator

Study Sites (5)

Práxis Pesquisa Medica

São Paulo, 09090-790, Brazil

Location

Hospital Universitario "Dr. José Eleiterio González", Colinia Mitras Centro

Monterrey, Nuevo Leon Mexico, C.P 64460, Mexico

Location

University Hospital Basel, Division of Internal Medicine

Basel, 4031, Switzerland

Location

Kantonsspital St. Gallen, Klinik für Infektiologie/Spitalhygiene

Sankt Gallen, 9007, Switzerland

Location

Stadtspital Triemli, Departement Innere Medizin

Zurich, 8063, Switzerland

Location

Related Publications (2)

• Urwyler P, Leimbacher M, Charitos P, Moser S, Heijnen IAFM, Trendelenburg M, Thoma R, Sumer J, Camacho-Ortiz A, Bacci MR, Huber LC, Stussi-Helbling M, Albrich WC, Sendi P, Osthoff M. Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial. Front Immunol. 2023 Oct 27;14:1255292. doi: 10.3389/fimmu.2023.1255292. eCollection 2023.

  PMID: 37965347 DERIVED

• Urwyler P, Charitos P, Moser S, Heijnen IAFM, Trendelenburg M, Thoma R, Sumer J, Camacho-Ortiz A, Bacci MR, Huber LC, Stussi-Helbling M, Albrich WC, Sendi P, Osthoff M. Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of severe SARS-CoV-2 infection in hospitalized patients with COVID-19: A structured summary of a study protocol for a randomized, parallel-group, open-label, multi-center pilot trial (PROTECT-COVID-19). Trials. 2021 Jan 4;22(1):1. doi: 10.1186/s13063-020-04976-x.

  PMID: 33397449 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Cytokine Release Syndrome; Angioedemas, Hereditary; COVID-19

Interventions

conestat alfa

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Michael Osthoff, PD Dr. med.

  University Hospital Basel, Division of Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, open-label, parallel-group, controlled, multi-center clinical trial

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: June 4, 2020
• Study Start: August 6, 2020
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: November 9, 2021

Record last verified: 2021-11

Locations

BR (1); ME (1); CH (3)