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Coronavirus InfectionsPhase 2NCT04414631

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

A Phase 2 study testing Conestat alfa in people with Coronavirus Infections, run by University Hospital, Basel, Switzerland at 5 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Coronavirus Infections
What is being tested?
Conestat alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
5 sitesin 3 countries
Study dates
6 Aug 2020to 15 Sep 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 14Show fewer
  • 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

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

Switzerland3 sites

  • University Hospital Basel, Division of Internal Medicine

    Basel, 4031

  • Kantonsspital St. Gallen, Klinik für Infektiologie/Spitalhygiene

    Sankt Gallen, 9007

  • Stadtspital Triemli, Departement Innere Medizin

    Zurich, 8063

Other trials in Switzerland

Brazil1 site

  • Práxis Pesquisa Medica

    São Paulo, 09090-790

Other trials in Brazil

Mexico1 site

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

    Monterrey, Nuevo Leon Mexico, C.P 64460

Other trials in Mexico

About this study

Official title: 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).

Read the 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).

Being tested
Conestat alfa
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)
Medical subject headings
Coronavirus Infections, Cytokine Release Syndrome, Angioedemas, Hereditary, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Conestat alfaDrug

    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.

Study groups in NCT04414631
Study groupRoleWhat they receive
active treatment armActive comparatortreatment with conestat alfa in addition to standarf of care
Receives: Drug: Conestat alfa
Standard of care treatment armNo interventionStandard of care treatment established at the centers

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: on day 7

Secondary outcomes (3)

  1. Time to clinical improvement

    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)

    Measured: within 14 days after enrolment

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

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

    Measured: at 14 days after enrolment

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

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

    Measured: within 14 days after enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2020
  2. Study start6 Aug 2020
  3. Primary completion15 Sep 2021
  4. Study completion15 Sep 2021

Why it stopped: Aim to enroll 120 patients deemed not sufficient to show a difference in the primary outcome measure. Standard of care treatment recently changed in Switzerland adding further heterogeneity to trial population when including future participants.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, open-label, parallel-group, controlled, multi-center clinical trial
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04414631
Sponsor's protocol ID
2020-01252; me20Osthoff3
Status last verified
Nov 2021
First submitted
19 May 2020
Last updated
9 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37965347

  • 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.

    PubMed 33397449

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Conestat alfa in people with Coronavirus Infections, run by University Hospital, Basel, Switzerland at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Switzerland, Brazil, Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Aim to enroll 120 patients deemed not sufficient to show a difference in the primary outcome measure. Standard of care treatment recently changed in Switzerland adding further heterogeneity to trial population when including future participants.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease severity (time frame: on day 7). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04414631, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2021.

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