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

November 1, 2021 updated by: University Hospital, Basel, Switzerland

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).

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 09090-790
        • Praxis Pesquisa Medica
  • Mexico
    • Nuevo Leon Mexico
      • Monterey, Nuevo Leon Mexico, Mexico, C.P 64460
        • Hospital Universitario "Dr. José Eleiterio González", Colinia Mitras Centro
  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital Basel, Division of Internal Medicine
      • St. Gallen, Switzerland, 9007
        • Kantonsspital St. Gallen, Klinik für Infektiologie/Spitalhygiene
      • Zürich, Switzerland, 8063
        • Stadtspital Triemli, Departement Innere Medizin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: active treatment arm
treatment with conestat alfa in addition to standarf of care
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.
No Intervention: Standard of care treatment arm
Standard of care treatment established at the centers

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Disease severity
Time Frame: on day 7
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to clinical improvement
Time Frame: within 14 days after enrolment
Time to clinical improvement (time from randomisation to an improvement of two points on the seven-category WHO ordinal scale or live discharge from hospital, whichever came first)
within 14 days after enrolment
Proportion of participants alive and not having required invasive or non-invasive ventilation
Time Frame: at 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)
Time Frame: within 14 days after enrolment
Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of <300mmHg)
within 14 days after enrolment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in the ordinal WHO scale
Time Frame: from baseline over 14 days
Changes in the ordinal WHO scale
from baseline over 14 days
Length of hospital stay in survivors
Time Frame: until day 28
Length of hospital stay in survivors
until day 28
Proportion of participants progressing to mechanical ventilation
Time Frame: on day 7 and day 14
Proportion of participants progressing to mechanical ventilation
on day 7 and day 14
Proportion of participants requiring ICU treatment
Time Frame: on day 7 and 14
Proportion of participants requiring ICU treatment
on day 7 and 14
Length of ICU stay
Time Frame: until day 28
Length of ICU stay
until day 28
28 Ventilator-free days
Time Frame: until day 28
28 Ventilator-free days
until day 28
All-cause mortality
Time Frame: time from randomisation to death within four weeks
All-cause mortality
time from randomisation to death within four weeks
Changes in biomarker level CRP (mg/l)
Time Frame: until day 14
Changes in biomarker level CRP
until day 14
Changes in biomarker level LDH (U/l)
Time Frame: until day 14
Changes in biomarker level LDH
until day 14
Changes in biomarker level D- Dimer (yg/ml)
Time Frame: until day 14
Changes in biomarker level D-Dimer
until day 14
Changes in biomarker level Ferritin (ng/ml)
Time Frame: until day 14
Changes in biomarker level Ferritin
until day 14
Changes in biomarker level Interleukin 6 (IL- 6) (pg/ml)
Time Frame: until day 14
Changes in biomarker level IL-6
until day 14
Changes in lymphocyte count (cells per microliter of blood)
Time Frame: until day 14
Changes in lymphocyte count
until day 14
Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples
Time Frame: time from enrolment to first of 2 negative assays at least 12 hours apart
Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples
time from enrolment to first of 2 negative assays at least 12 hours apart
Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins
Time Frame: within 14 days
Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins
within 14 days
Time to defervescence (temperature <38.0°C)
Time Frame: sustained for at least 48 hours
Time to defervescence (temperature <38.0°C)
sustained for at least 48 hours
Time to clinical improvement (defervescence, normalization of oxygen saturation (>93%) and respiratory rate) until day 28
Time Frame: until day 28
Time to clinical improvement (defervescence, normalization of oxygen saturation (>93%) and respiratory rate)
until day 28
Duration of supplemental oxygen
Time Frame: until day 28
Duration of supplemental oxygen
until day 28
Change in pharmacokinetics of conestat alfa
Time Frame: at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date
Peak serum concentration of conestat alfa will be measured
at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date
Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)
Time Frame: at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date
Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)
at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Basel, Switzerland

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pharming Technologies B.V.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 6, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 15, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 15, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 19, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 2, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 4, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-01252; me20Osthoff3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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