Phase 2
Completed N=81
Zilucoplan® in Improving Oxygenation, Short-, Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure
Source: ClinicalTrials.gov NCT04382755 ↗Enrolled (actual)
81
Serious AEs
19.2%
Results posted
Sep 2023
Primary outcomePrimary: Change in Oxygenation — 56.4; 20.6; 123.5; 83.7 mmHg
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.
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Oxygenation |
114.6; 146.7; 58.6; 86.9 | — |
| SECONDARY Mean Change in 6-point Ordinal Scale Change for Clinical Improvement |
0.1; 0.1; 1.2; 1; 1.7; 1.3 | — |
| SECONDARY Number of Days With Hypoxia |
13; 10 | — |
| SECONDARY Number of Days of Supplemental Oxygen Use |
13; 10 | — |
| SECONDARY Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic |
7; 3 | — |
| SECONDARY Number of Days With Fever |
7; 4 | — |
| SECONDARY Mean Change in CRP Levels Between Day 1 and Day 6 |
-89.6; -100 | — |
| SECONDARY Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First) |
-91.0; -96.2 | — |
| SECONDARY Mean Change in Ferritin Levels Between Day 1 and Day 6 |
-544.4; -282.3 | — |
| SECONDARY Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First) |
-201.0; -303.9 | — |
| SECONDARY Number of Participants With Adverse Events |
39; 17 | — |
| SECONDARY Number of Participants With Serious Adverse Events |
10; 5 | — |
| SECONDARY Number of Participants With SUSAR's (Suspected Unexpected Serious Adverse Reaction) |
0; 0 | — |
| SECONDARY Number of Participants With SAR's (Serious Adverse Reaction) |
0; 0 | — |
| SECONDARY Duration of Hospital Stay |
15; 13 | — |
| SECONDARY Duration of Hospital Stay in Survivors |
15; 12 | — |
| SECONDARY 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) |
21; 10; 11; 6; 11; 5 | — |
| SECONDARY 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) |
33; 12; 5; 1; 5; 4 | — |
| SECONDARY Number of Participants With Nosocomial Bacterial or Invasive Fungal Infection for 28 Days (Phone Call) After Enrollment in Trial |
12; 4 | — |
| SECONDARY 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 |
15; 12 | — |
| SECONDARY Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants in Each Category of the WHO Performance Scale |
23; 10; 18; 7; 2; 1 | — |
| SECONDARY Result of 6 Minute Walk Test |
539.7; 490.6 | — |
| SECONDARY All-cause Mortality Rate (Excluding Group That Entered During Ventilation) |
3; 5 | — |
| SECONDARY All-cause Mortality Rate (Including Group That Entered During Ventilation) |
5; 5 | — |
| SECONDARY All Cause Mortality for the Entire Study Population |
7; 5 | — |
Eligibility Criteria
Inclusion Criteria
- 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 ( 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 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
Exclusion Criteria
- 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
- 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)
Data sourced from ClinicalTrials.gov (NCT04382755). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.