COVID-19Phase 2ZILU-COVNCT04382755
Zilucoplan® in Improving Oxygenation, Short-, Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure
A Phase 2 study testing Zilucoplan® in people with COVID-19, run by University Hospital, Ghent at 9 sites in Belgium.
Trial summary
The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Zilucoplan®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 9 sitesBelgium
- Study dates
- 22 May 2020to 9 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recent (≥6 days and ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
- COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period. For patients with a negative SARS-CoV-2 PCR and either a positive SARS-CoV-2 antigen or antibody test, the presence of suggestive lesions for COVID-19 on chest-CT scan is mandatory.
- In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable SARS-CoV-2-infected. In all cases, this needs confirmation by later seroconversion.
- Presence of hypoxia defined as :
- O2 saturation below 93% on minimal 2l/min O2 therapy; and/or
- PaO2/FiO2 below 350 mmHg (Strongly recommended: patient in upright position, after minimal 3 minutes without supplemental oxygen; In ventilated patients or ECMO patients PaO2 can be taken from invasive arterial line and FiO2 taken directly from mechanical ventilation settings).
Show all 20Show fewer
- Signs of acute lung injury and/or cytokine release syndrome defined as ANY of the following
- serum ferritin concentration >1000 mcg/L and rising since last 24h
- single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device (Optiflow) or non-invasive or invasive mechanical ventilation
- lymphopenia defined as <800 lymphocytes/microliter and two of the following extra criteria
- Ferritin > 700 mcg/L and rising since last 24h
- Increased LDH (above 300 IU/L) and rising since last 24h
- D-Dimers > 1000 ng/mL and rising since last 24h
- CRP above 70 mg/L and rising since last 24h and absence of bacterial infection
- if three of the above are present at admission, no need to document 24h rise
- Low dose Chest CT or HRCT or Angio Chest CT scan showing bilateral infiltrates within last 2 days prior to randomisation
- Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients
- Age ≥ 18 years
- Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Women of childbearing potential must consistently and correctly use (during the entire treatment period and 4weeks after last Zilucoplan® administration ) at least 1 highly effective method for contraception.
- Willing and able to provide informed consent or legal representative willing to provide informed consent
Who cannot join
- Patients with known history of serious allergic reactions, including anaphylaxis, to Zilucoplan® or inability to receive antibiotic prophylaxis due to allergy to ALL of the antibiotics that can be given for prophylaxis of meningococcal disease
- History of active or past meningococcal disease
- Invasive mechanical ventilation > 24 h at randomization
- Patient on ECMO at screening
- Clinical frailty scale above 3 before onset of the COVID-19 episode
- Weight below 54 kg as measured max 1 week prior to inclusion
Show all 16Show fewer
- Weight above 150 kg as measured max 1 week prior to inclusion
- Active bacterial or fungal infection
- Unlikely to survive beyond 48h
- Neutrophil count below 1500 cells/microliter
- Platelets below 50.000/microliter
- Patients enrolled in another investigational drug study
- Patients on high dose systemic steroids (> 8 mg methylprednisolone or equivalent for more than 1 month) or other moderately immunosuppressive drugs (in the opinion of the investigator) for COVID19 unrelated disorder
- Patients on current complement inhibiting drugs
- Serum transaminase levels >5 times upper limit of normal, unless there are clear signs of cytokine release syndrome defined by LDH >300 IU/L and ferritin >700 ng/ml
- Pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Belgium9 sites
OLVZ Aalst
Aalst, 9300
AZ Sint Jan Brugge
Bruges, 8000
Erasmus University Hospital
Brussels, 1070
AZ Sint-Lucas
Ghent, 9000
University Hospital Ghent
Ghent, 9000
Jan Yperman Ziekenhuis Ieper
Ieper, 128900
University Hospital Liège
Liège, 4000
AZ Delta
Roeselare, 8800
AZ Vesalius
Tongeren, 3700
About this study
Official title: A Prospective Randomized Open-label Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and Short-and Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure
The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone.
In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first.
Read more
The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.
Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
Read the detailed description
This investigator-initiated trial is a phase 2 academic, prospective, 2:1 randomized, open-label, multicenter interventional study designed to investigate the efficacy of subcutaneous Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. The hypothesis of the proposed intervention is that Zilucoplan® has profound effects on inhibiting acute lung injury induced by COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.
We will randomize patients with confirmed COVID19 with acute hypoxic respiratory failure (O2 saturation below 93% on minimal 2l/min O2 therapy; and/or PaO2/FiO2 below 350 mmHg) to receive up to 14 days of SC Zilucoplan® on top of standard of care (active group A), or to receive standard of care treatment (control group B). Randomization will be done at a 2:1 ratio active: control group. In the active group A, patients will additionally receive daily antibiotics (daily 3rd generation cephalosporin IV while in hospital, followed by oral ciprofloxacin while discharged) as primary prophylaxis against meningococcal disease until 14 days after the last dose of Zilucoplan®. Control group B will receive standard of care and prophylactic antibiotics (3rd generation cephalosporin IV) for only 1 week (or until hospital discharge whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. In case of allergies to these antibiotics, or on clinical indication, these antibiotics may be switched to antibiotics that also cover Neisseria meningitidis.
To measure the effectiveness of Zilucoplan® on restoring lung homeostasis, the primary endpoint of this intervention is measuring change in oxygenation parameters comparing baseline values (pretreatment) to values predose day 6 and to values at day 15 (or discharge whichever comes first) post-randomizationin group A and group B and the differences in these values between group A and group B.
- Conditions
- COVID-19
- Being tested
- Zilucoplan®, Placebo
- Keywords
- Acute Lung Injury, Hypoxia, Corona virus, COVID-19, SARS (Severe Acute Respiratory Syndrome), Acute Respiratory Distress Syndrome, ARDS
- Medical subject headings
- COVID-19, Acute Lung Injury, Hypoxia, Severe Acute Respiratory Syndrome, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zilucoplan®Drug
14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®
PlaceboDrug
standard of care treatment + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
| Study group | Role | What they receive |
|---|---|---|
| Group A (active) | Active comparator | Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Receives: Drug: Zilucoplan® |
| Group B (control) | Placebo comparator | Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Oxygenation
defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measured: at predose, day 6 and day 15 (or at discharge, whichever comes first)
Secondary outcomes (25)
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement
6-point ordinal scale defined as
- Death
- Hospitalized, on invasive mechanical ventilation or ECMO;
- Hospitalized, on non-invasive ventilation
- Hospitalized, requiring supplemental oxygen
- Hospitalized, not requiring supplemental oxygen
- Not hospitalized
Measured: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).
Number of Days With Hypoxia
defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen
Measured: during hospital admission (up to 28 days)
Number of Days of Supplemental Oxygen Use
Measured: during hospital admission (up to 28 days)
Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic
Measured: during hospital admission (up to 28 days)
Number of Days With Fever
defined as 37.1°C or more
Measured: during hospital admission (up to 28 days)
Mean Change in CRP Levels Between Day 1 and Day 6
Measured: day 1, day 6
Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First)
Measured: day 1, day 15
Mean Change in Ferritin Levels Between Day 1 and Day 6
Measured: day 1, day 6
Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First)
Measured: day 1, day 15
Number of Participants With Adverse Events
Any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: during hospital admission (up to 28 days)
Number of Participants With Serious Adverse Events
A serious adverse event is any untoward medical occurrence that:
- results in death
- is life-threatening
- requires inpatient hospitalisation or prolongation of existing hospitalisation
- results in persistent or significant disability/incapacity
- consists of a congenital anomaly or birth defect Other 'important medical events' may also be considered serious if they jeopardise the subject or require an intervention to prevent one of the above consequences.
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.
Measured: at 10-20 weeks follow-up
Number of Participants With SUSAR's (Suspected Unexpected Serious Adverse Reaction)
A serious adverse reaction, the nature and severity of which is not consistent with the information about the medicinal product in question set out:
- in the case of a product with a marketing authorisation, in the summary of product characteristics (SmPC) for that product
- in the case of any other investigational medicinal product, in the investigator's brochure (IB) relating to the study in question
Measured: during hospital admission (up to 28 days)
Number of Participants With SAR's (Serious Adverse Reaction)
An adverse event that is both serious and, in the opinion of the reporting Investigator, believed with reasonable probability to be due to one of the study treatments, based on the information provided.
Measured: during hospital admission (up to 28 days)
Duration of Hospital Stay
Measured: at 12-22 weeks follow-up
Duration of Hospital Stay in Survivors
Measured: at 12-22 weeks follow-up
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 6 (or on Discharge, Whichever is First)
The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points.
Measured: day 1, day 6 or on discharge, whichever is first
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 15 (or on Discharge, Whichever is First)
The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points.
Measured: day 1, day 15 or on discharge, whichever is first
Number of Participants With Nosocomial Bacterial or Invasive Fungal Infection for 28 Days (Phone Call) After Enrollment in Trial
Measured: day 28
Median Time to at Least a 2-point Improvement on the 6-point Ordinal Scale or Discharge During the 28-day Assessment Period (Range) - Days
The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome
Measured: Day 28
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement
The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome
Measured: at 12-22 weeks follow-up
Number of Participants in Each Category of the WHO Performance Scale
The WHO performance status classification categorises patients as:
0: able to carry out all normal activity without restriction
- restricted in strenuous activity but ambulatory and able to carry out light work
- ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
- symptomatic and in a chair or in bed for greater than 50% of the day but not bedridden
- completely disabled; cannot carry out any self-care; totally confined to bed or chair.
Measured: during hospital admission (up to 28 days)
Result of 6 Minute Walk Test
Distance in 6 minute walk test. The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Total distance in meters. A higher score has a better outcome
Measured: at 12-22 weeks follow-up
All-cause Mortality Rate (Excluding Group That Entered During Ventilation)
Measured: at day 28
All-cause Mortality Rate (Including Group That Entered During Ventilation)
Measured: at day 28
All Cause Mortality for the Entire Study Population
Measured: at follow up 12-22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start22 May 2020
- Primary completion29 Dec 2020
- Study completion9 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Pharma
- Responsible party
- Principal investigator, Bart N. Lambrecht, University Hospital, Ghent
- Investigators
- Bart N Lambrecht, MDPhD, Principal investigator, University Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04382755
- Sponsor's protocol ID
- ZILU-COV
- Acronym
- ZILU-COV
- Status last verified
- Sep 2023
- First submitted
- 7 May 2020
- Last updated
- 14 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
De Leeuw E, Van Damme KFA, Declercq J, Bosteels C, Maes B, Tavernier SJ, Detalle L, Smart T, Glatt S, Debeuf N, Deckers J, Lameire S, Vandecasteele SJ, De Neve N, Demedts IK, Govaerts E, Knoop C, Vanhove K, Moutschen M, Terryn W, Depuydt P, Van Braeckel E, Haerynck F, Hendrickx TCJ, Parrein V, Lalla M, Brittain C, Lambrecht BN. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial. Respir Res. 2022 Aug 9;23(1):202. doi: 10.1186/s12931-022-02126-2.
PubMed 35945604Declercq J, Bosteels C, Van Damme K, De Leeuw E, Maes B, Vandecauter A, Vermeersch S, Delporte A, Demeyere B, Vuylsteke M, Lalla M, Smart T, Detalle L, Bouw R, Streffer J, Degeeter T, Vergotte M, Guisez T, Van Braeckel E, Van Der Straeten C, Lambrecht BN. Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 19;21(1):934. doi: 10.1186/s13063-020-04884-0.
PubMed 33213529
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Open-label Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and Short-and Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure
- ClinicalTrials.gov ID
- NCT04382755
- Acronym / sponsor ID
- ZILU-COV / ZILU-COV
- Conditions
- COVID-19
- Keywords
- Acute Lung Injury, Hypoxia, Corona virus, COVID-19, SARS (Severe Acute Respiratory Syndrome), Acute Respiratory Distress Syndrome, ARDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- UCB Pharma
- Study start
- 22 May 2020 (actual)
- Primary completion
- 29 Dec 2020 (actual)
- Study completion
- 9 Apr 2021 (actual)
- First posted
- 11 May 2020 (actual)
- Results
- Posted 14 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone.
In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first.
The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.
Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
Detailed description
This investigator-initiated trial is a phase 2 academic, prospective, 2:1 randomized, open-label, multicenter interventional study designed to investigate the efficacy of subcutaneous Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. The hypothesis of the proposed intervention is that Zilucoplan® has profound effects on inhibiting acute lung injury induced by COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.
We will randomize patients with confirmed COVID19 with acute hypoxic respiratory failure (O2 saturation below 93% on minimal 2l/min O2 therapy; and/or PaO2/FiO2 below 350 mmHg) to receive up to 14 days of SC Zilucoplan® on top of standard of care (active group A), or to receive standard of care treatment (control group B). Randomization will be done at a 2:1 ratio active: control group. In the active group A, patients will additionally receive daily antibiotics (daily 3rd generation cephalosporin IV while in hospital, followed by oral ciprofloxacin while discharged) as primary prophylaxis against meningococcal disease until 14 days after the last dose of Zilucoplan®. Control group B will receive standard of care and prophylactic antibiotics (3rd generation cephalosporin IV) for only 1 week (or until hospital discharge whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. In case of allergies to these antibiotics, or on clinical indication, these antibiotics may be switched to antibiotics that also cover Neisseria meningitidis.
To measure the effectiveness of Zilucoplan® on restoring lung homeostasis, the primary endpoint of this intervention is measuring change in oxygenation parameters comparing baseline values (pretreatment) to values predose day 6 and to values at day 15 (or discharge whichever comes first) post-randomizationin group A and group B and the differences in these values between group A and group B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (active) | Active comparator | Drug: Zilucoplan®Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® |
| Group B (control) | Placebo comparator | Drug: PlaceboStandard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Recent (≥6 days and ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
- COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period. For patients with a negative SARS-CoV-2 PCR and either a positive SARS-CoV-2 antigen or antibody test, the presence of suggestive lesions for COVID-19 on chest-CT scan is mandatory.
- In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable SARS-CoV-2-infected. In all cases, this needs confirmation by later seroconversion.
- Presence of hypoxia defined as :
- Signs of acute lung injury and/or cytokine release syndrome defined as ANY of the following
Key exclusion criteria (16 listed)
- Patients with known history of serious allergic reactions, including anaphylaxis, to Zilucoplan® or inability to receive antibiotic prophylaxis due to allergy to ALL of the antibiotics that can be given for prophylaxis of meningococcal disease
- History of active or past meningococcal disease
- Invasive mechanical ventilation > 24 h at randomization
- Patient on ECMO at screening
- Clinical frailty scale above 3 before onset of the COVID-19 episode
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zilucoplan®14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan® | Drug | Group A (active) |
| Placebostandard of care treatment + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) | Drug | Group B (control) |
Primary outcome
Change in Oxygenation
Time frame: at predose, day 6 and day 15 (or at discharge, whichever comes first)
defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
25 secondary outcomes
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement
Time frame: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).
Number of Days With Hypoxia
Time frame: during hospital admission (up to 28 days)
Number of Days of Supplemental Oxygen Use
Time frame: during hospital admission (up to 28 days)
Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic
Time frame: during hospital admission (up to 28 days)
Number of Days With Fever
Time frame: during hospital admission (up to 28 days)
Mean Change in CRP Levels Between Day 1 and Day 6
Time frame: day 1, day 6
Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First)
Time frame: day 1, day 15
Mean Change in Ferritin Levels Between Day 1 and Day 6
Time frame: day 1, day 6
Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First)
Time frame: day 1, day 15
Number of Participants With Adverse Events
Time frame: during hospital admission (up to 28 days)
Number of Participants With Serious Adverse Events
Time frame: at 10-20 weeks follow-up
Number of Participants With SUSAR's (Suspected Unexpected Serious Adverse Reaction)
Time frame: during hospital admission (up to 28 days)
Number of Participants With SAR's (Serious Adverse Reaction)
Time frame: during hospital admission (up to 28 days)
Duration of Hospital Stay
Time frame: at 12-22 weeks follow-up
Duration of Hospital Stay in Survivors
Time frame: at 12-22 weeks follow-up
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 6 (or on Discharge, Whichever is First)
Time frame: day 1, day 6 or on discharge, whichever is first
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 15 (or on Discharge, Whichever is First)
Time frame: day 1, day 15 or on discharge, whichever is first
Number of Participants With Nosocomial Bacterial or Invasive Fungal Infection for 28 Days (Phone Call) After Enrollment in Trial
Time frame: day 28
Median Time to at Least a 2-point Improvement on the 6-point Ordinal Scale or Discharge During the 28-day Assessment Period (Range) - Days
Time frame: Day 28
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement
Time frame: at 12-22 weeks follow-up
Number of Participants in Each Category of the WHO Performance Scale
Time frame: during hospital admission (up to 28 days)
Result of 6 Minute Walk Test
Time frame: at 12-22 weeks follow-up
All-cause Mortality Rate (Excluding Group That Entered During Ventilation)
Time frame: at day 28
All-cause Mortality Rate (Including Group That Entered During Ventilation)
Time frame: at day 28
All Cause Mortality for the Entire Study Population
Time frame: at follow up 12-22 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35945604De Leeuw E, Van Damme KFA, Declercq J, Bosteels C, Maes B, Tavernier SJ, Detalle L, Smart T, Glatt S, Debeuf N, Deckers J, Lameire S, Vandecasteele SJ, De Neve N, Demedts IK, Govaerts E, Knoop C, Vanhove K, Moutschen M, Terryn W, Depuydt P, Van Braeckel E, Haerynck F, Hendrickx TCJ, Parrein V, Lalla M, Brittain C, Lambrecht BN. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial. Respir Res. 2022 Aug 9;23(1):202. doi: 10.1186/s12931-022-02126-2.
- Derived from this study: PubMed 33213529Declercq J, Bosteels C, Van Damme K, De Leeuw E, Maes B, Vandecauter A, Vermeersch S, Delporte A, Demeyere B, Vuylsteke M, Lalla M, Smart T, Detalle L, Bouw R, Streffer J, Degeeter T, Vergotte M, Guisez T, Van Braeckel E, Van Der Straeten C, Lambrecht BN. Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 19;21(1):934. doi: 10.1186/s13063-020-04884-0.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bart N Lambrecht, MDPhD principal investigator
University Ghent
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zilucoplan® in people with COVID-19, run by University Hospital, Ghent at 9 sites in Belgium.
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 20 inclusion and 16 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: finished, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Belgium. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 14 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Oxygenation (time frame: at predose, day 6 and day 15 (or at discharge, whichever comes first)). 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 NCT04382755, 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 14 Sep 2023.