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NCT04382755: ZILU-COV

Zilucoplan® in Improving Oxygenation, Short-, Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure

Completed Phase 2 Results posted Last updated 14 September 2023
What this trial tests

Phase 2 trial testing Zilucoplan® in COVID-19 in 81 participants. Completed in 9 April 2021.

Timeline
22 May 2020
Primary endpoint
29 December 2020
9 April 2021

Quick facts

Lead sponsorUniversity Hospital, Ghent
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment81
Start date22 May 2020
Primary completion29 December 2020
Estimated completion9 April 2021
Sites9 locations across Belgium

Drugs / interventions tested

Conditions studied

Sponsor

University Hospital, Ghent

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Oxygenation Primary · 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

change from baseline in PaO2/FiO2 day 6
GroupValue95% CI
Group A (Active)56.431.9 – 80.9
Group B (Control)20.617.3 – 58.5
change from baseline in PaO2/FiO2 day 15
GroupValue95% CI
Group A (Active)123.594.3 – 152.7
Group B (Control)83.739.0 – 128.4
change from baseline in a/A PO2 day 6
GroupValue95% CI
Group A (Active)0.100.06 – 0.15
Group B (Control)0.040.04 – 0.11
change from baseline in a/A PO2 day 15
GroupValue95% CI
Group A (Active)0.250.19 – 0.31
Group B (Control)0.170.08 – 0.26
Change in Oxygenation Primary · 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

(A-a) gradient day 6
GroupValue95% CI
Group A (Active)114.692.6 – 141.9
Group B (Control)146.7105.4 – 204.3
(A-a) gradient day 15
GroupValue95% CI
Group A (Active)58.644.9 – 76.5
Group B (Control)86.957.9 – 130.6
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement Secondary · between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

6-point ordinal scale defined as 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO; 3. Hospitalized, on non-invasive ventilation 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen 6. Not hospitalized

mean change in 6-point ordinal scale change day 6
GroupValue95% CI
Group A (Active)0.1± 1.0
Group B (Control)0.1± 0.9
mean change in 6-point ordinal scale change day 15
GroupValue95% CI
Group A (Active)1.2± 1.4
Group B (Control)1± 1.5
mean change in 6-point ordinal scale change day 28
GroupValue95% CI
Group A (Active)1.7± 1.5
Group B (Control)1.3± 1.8
Number of Days With Hypoxia Secondary · during hospital admission (up to 28 days)

defined as SpO2 \< 93% breathing room air or the dependence on supplemental oxygen

GroupValue95% CI
Group A (Active)133 – 28
Group B (Control)102 – 28
Number of Days of Supplemental Oxygen Use Secondary · during hospital admission (up to 28 days)
GroupValue95% CI
Group A (Active)133 – 28
Group B (Control)102 – 28
Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic Secondary · during hospital admission (up to 28 days)
GroupValue95% CI
Group A (Active)71 – 28
Group B (Control)31 – 28
Number of Days With Fever Secondary · during hospital admission (up to 28 days)

defined as 37.1°C or more

GroupValue95% CI
Group A (Active)70 – 28
Group B (Control)40 – 20
Mean Change in CRP Levels Between Day 1 and Day 6 Secondary · day 1, day 6
GroupValue95% CI
Group A (Active)-89.6± 91.5
Group B (Control)-100± 61.9
Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First) Secondary · day 1, day 15
GroupValue95% CI
Group A (Active)-91.0± 106.3
Group B (Control)-96.2± 98.4
Mean Change in Ferritin Levels Between Day 1 and Day 6 Secondary · day 1, day 6
GroupValue95% CI
Group A (Active)-544.4± 1489.9
Group B (Control)-282.3± 517.0
Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First) Secondary · day 1, day 15
GroupValue95% CI
Group A (Active)-201.0± 6204.5
Group B (Control)-303.9± 948.4
Number of Participants With Adverse Events Secondary · during hospital admission (up to 28 days)

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.

GroupValue95% CI
Group A (Active)39
Group B (Control)17

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group A (Active)
Serious: 10/54 (19%)
Deaths: 7/54
Group B (Control)
Serious: 5/24 (21%)
Deaths: 5/24

Serious adverse events (18 terms)

ReactionSystemGroup A (Active)Group B (Control)
Respiratory failureRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
HypercapniaRespiratory, thoracic and mediastinal disorders
hypoxiaRespiratory, thoracic and mediastinal disorders
Aspergillus infectionImmune system disorders
hypoxic-sichaemic encephalopathyNervous system disorders
deathGeneral disorders
multiple organ dysfunction syndromeGeneral disorders
acute kidney injuryRenal and urinary disorders
thrombosis in deviceProduct Issues
bronchopulmonary aspergillusInfections and infestations
Respiratory tract infection bacterialInfections and infestations
covid-19Infections and infestations
cytomegalovirus infectionInfections and infestations
enterococcal sepsisInfections and infestations
pneumoniaInfections and infestations
sepsisInfections and infestations
septic shockInfections and infestations
Other adverse events (14 terms — click to expand)

ReactionSystemGroup A (Active)Group B (Control)
hypertensionVascular disorders
constipationGastrointestinal disorders
anxietyPsychiatric disorders
insomniaPsychiatric disorders
pneumoniaInfections and infestations
alanine animontransferase increasedInvestigations
anemiaBlood and lymphatic system disorders
aspartate animontransferase increasedInvestigations
Respiratory failureRespiratory, thoracic and mediastinal disorders
deliriumPsychiatric disorders
hyperglycemiaMetabolism and nutrition disorders
hypoalbuminiaMetabolism and nutrition disorders
pneumonia pseudomonalRespiratory, thoracic and mediastinal disorders
decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Respiratory failure, Cardiac arrest, Hypercapnia, hypoxia, Aspergillus infection, hypoxic-sichaemic encephalopathy, death, multiple organ dysfunction syndrome.

Data from ClinicalTrials.gov NCT04382755 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions.
    Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, et al · · 2020 · cited 246× · PMID 32687918 · DOI 10.1016/j.lfs.2020.118102
  2. The state of complement in COVID-19.
    Afzali B, Noris M, Lambrecht BN, Kemper C. · · 2022 · cited 224× · PMID 34912108 · DOI 10.1038/s41577-021-00665-1
  3. COVID-19: A review of therapeutic strategies and vaccine candidates.
    Izda V, Jeffries MA, Sawalha AH. · · 2021 · cited 159× · PMID 33217545 · DOI 10.1016/j.clim.2020.108634
  4. Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial.
    Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, et al · · 2020 · cited 149× · PMID 33015643 · DOI 10.1016/s2665-9913(20)30341-6
  5. Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes.
    England JT, Abdulla A, Biggs CM, Lee AYY, et al · · 2021 · cited 124× · PMID 32425294 · DOI 10.1016/j.blre.2020.100707
  6. Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management.
    Aslan A, Aslan C, Zolbanin NM, Jafari R. · · 2021 · cited 92× · PMID 34872623 · DOI 10.1186/s41479-021-00092-9
  7. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
    Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
  8. Translational medicine for acute lung injury.
    Zhang J, Guo Y, Mak M, Tao Z. · · 2024 · cited 59× · PMID 38183140 · DOI 10.1186/s12967-023-04828-7

Verify or expand the search:

Other trials of Zilucoplan®

Trials testing the same drug.

Other recruiting trials for COVID-19

Currently open trials in the same condition.

Other University Hospital, Ghent trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04382755.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing