NCT04331808: CORIMUNO-TOC

CORIMUNO-19 - Tocilizumab Trial - TOCI (CORIMUNO-TOCI)

Completed Phase 2 Results posted Last updated 12 June 2025

What this trial tests

Phase 2 trial testing Tocilizumab in Corona Virus Infection in 228 participants. Completed in 9 November 2020.

Timeline

30 March 2020

Primary endpoint
4 May 2020

9 November 2020

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	228
Start date	30 March 2020
Primary completion	4 May 2020
Estimated completion	9 November 2020
Sites	8 locations across France

Drugs / interventions tested

• Tocilizumab (tocilizumab) — full drug profile →

Conditions studied

• Corona Virus Infection — all drugs for Corona Virus Infection →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Corona Virus Infection. 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.

Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) Primary · 4 days

Percentage of participants who has died or needed non-invasive or mechanical ventilation by day 4 (WHO clinical progression scale \> 5). A patient with new do-not-resuscitate order at day 4 will be considered as with a score \> 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2\>=150 OR SpO2/FIO2\>=200: 7 Mecha

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	19
Standard of Care -- Severe COVID Population (WHO-CPS =5)	28

Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline) Primary · Day 1 to Day 14

Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Percentage of non-invasive ventilation, mechanical ventilation or death. Thus, events considered are needing ventilator utilization (mechanical or non-invasive ventilation including high flow oxygen), or death. New do-not-resuscitate (DNR) order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	24	13 – 34
Standard of Care -- Severe COVID Population (WHO-CPS =5)	36	23 – 46

Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline) Primary · 4 days

Results are presented as the percentage not improved, so that an effective treatment would be associated with a decrease in percentage WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2\>=150 OR SpO2/FIO2\>=200: 7 Mechanical ventilation, (pO2/FIO2\<150 OR SpO2/FIO2\<200) OR vasopressors (norepinephrine \>0.3 micro

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	71
Standard of Care -- Critical COVID Population (WHO-CPS >5)	70

Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) Primary · Day 1 to Day 14

Cumulative incidence of successful tracheal extubation (defined as duration extubation \> 48h) at day 14 if patients have been intubated before day 14 ; or removal of Non Invasive Ventilation or high flow (for \> 48h) if they were included under oxygen by Non Invasive Ventilation or High flow (score 6) and remained without intubation. Death or new do-not-resuscitate order (if given after the inclusion of the patient) will be considered as a competing event.

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	47	32 – 60
Standard of Care -- Critical COVID Population (WHO-CPS >5)	42	27 – 56

Percentage of Participants Surviving (Overall Survival) Secondary · 14, 28 and 90 days

Percentage of participants surviving at 14, 28 and 90 days

Day 14

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	89	81 – 97
Standard of Care -- Severe COVID Population (WHO-CPS =5)	91	84 – 98
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	90	82 – 99
Standard of Care -- Critical COVID Population (WHO-CPS >5)	79	68 – 92

Day 28

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	89	81 – 97
Standard of Care -- Severe COVID Population (WHO-CPS =5)	88	80 – 96
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	84	74 – 95
Standard of Care -- Critical COVID Population (WHO-CPS >5)	77	65 – 90

Day 90

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	89	81 – 97
Standard of Care -- Severe COVID Population (WHO-CPS =5)	84	75 – 93
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	76	64 – 89
Standard of Care -- Critical COVID Population (WHO-CPS >5)	70	57 – 85

WHO Progression Scale Secondary · 4, 7 and 14 days

WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2\>=150 OR SpO2/FIO2\>=200: 7 Mechanical ventilation, (pO2/FIO2\<150 OR SpO2/FIO2\<200) OR vasopressors (norepinephrine \>0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2\<150 AND vasopressors (norepinephrine \>0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 1

Day 4

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	5	5 – 5
Standard of Care -- Severe COVID Population (WHO-CPS =5)	5	5 – 6
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	7	7 – 8
Standard of Care -- Critical COVID Population (WHO-CPS >5)	8	7 – 8

Day 7

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	5	5 – 5
Standard of Care -- Severe COVID Population (WHO-CPS =5)	5	5 – 6
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	7	5 – 8
Standard of Care -- Critical COVID Population (WHO-CPS >5)	8	7 – 8

Day 14

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	2	2 – 5
Standard of Care -- Severe COVID Population (WHO-CPS =5)	4	2 – 7
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	7	5 – 8
Standard of Care -- Critical COVID Population (WHO-CPS >5)	7	5 – 9

Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) Secondary · 28 days

28-day ventilator free-days

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	12.8	± 10.7
Standard of Care -- Critical COVID Population (WHO-CPS >5)	10.3	± 11.1

Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency Secondary · Day 28, 90

Time to oxygen supply independency

Day 28

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	89	78 – 95
Standard of Care -- Severe COVID Population (WHO-CPS =5)	75	62 – 83
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	59	44 – 72
Standard of Care -- Critical COVID Population (WHO-CPS >5)	49	33 – 63

Day 90

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	69	53 – 80
Standard of Care -- Critical COVID Population (WHO-CPS >5)	64	47 – 77

Cumulative Incidence (Percentage of Participants) of Discharge From Hospital Secondary · 28, 90 days

Time to discharge from hospital

Day 28

Group	Value	95% CI
TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)	83	70 – 90
Standard of Care -- Severe COVID Population (WHO-CPS =5)	73	61 – 82
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	55	40 – 68
Standard of Care -- Critical COVID Population (WHO-CPS >5)	42	27 – 56

Day 90

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	70	54 – 82
Standard of Care -- Critical COVID Population (WHO-CPS >5)	60	44 – 74

Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) Secondary · 28, 90 days

Time to discharge from Intensive Care Unit

Day 28

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	72	55 – 84
Standard of Care -- Critical COVID Population (WHO-CPS >5)	60	42 – 74

Day 90

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	84	66 – 93
Standard of Care -- Critical COVID Population (WHO-CPS >5)	83	63 – 93

PaO2/FIO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) Secondary · day 1 to day 14

Evolution of PaO2/FiO2 ratio PaO2 is partial pressure of arterial oxygen expressed in mmHg. FiO2 is fraction of inspired oxygen (for instance, 0.33 for 33% oxygen) with no units. PaO2/FiO2 ratio is expressed in mmHg.

Day 1

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	155.1	98.4 – 201.8
Standard of Care -- Critical COVID Population (WHO-CPS >5)	135.0	98.8 – 184.7

Day 4

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	144.0	95.7 – 214.0
Standard of Care -- Critical COVID Population (WHO-CPS >5)	143.8	96.2 – 175.2

Day7

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	126.0	89.7 – 190.0
Standard of Care -- Critical COVID Population (WHO-CPS >5)	142.8	105.5 – 199.0

Day 14

Group	Value	95% CI
TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)	153.7	141.2 – 189.5
Standard of Care -- Critical COVID Population (WHO-CPS >5)	94.0	86.2 – 129.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were systematically assessed at Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 while participants were inpatient, and at Days 28 and 60 and 90.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5)

Serious: 20/63 (32%)

Deaths: 7/63

Standard of Care -- Severe COVID Population (WHO-CPS =5)

Serious: 29/67 (43%)

Deaths: 11/67

TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5)

Serious: 31/49 (63%)

Deaths: 12/49

Standard of Care -- Critical COVID Population (WHO-CPS >5)

Serious: 27/43 (63%)

Deaths: 13/43

Serious adverse events (47 terms)

Reaction	System	TOCILIZUMAB -- Severe COVI…	Standard of Care -- Severe…	TOCILIZUMAB -- Critical CO…	Standard of Care -- Critic…
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Bacterial sepsis	Infections and infestations	—	—	—	—
Hepatic cytolysis	Hepatobiliary disorders	—	—	—	—
Anemia	General disorders	—	—	—	—
Pulmonary embolism	Vascular disorders	—	—	—	—
Acute renal failure	Renal and urinary disorders	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Cholestasis	Hepatobiliary disorders	—	—	—	—
Arterial ischemia	Cardiac disorders	—	—	—	—
Fungal sepsis	Infections and infestations	—	—	—	—
Hemorrhagic stroke	Nervous system disorders	—	—	—	—
Ischemic stroke	Nervous system disorders	—	—	—	—
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Hyperlipasemia	Gastrointestinal disorders	—	—	—	—
Multiple organ failure	General disorders	—	—	—	—
Fever	Infections and infestations	—	—	—	—
Hyperkaliemia	Renal and urinary disorders	—	—	—	—
Hyperglycaemia	Endocrine disorders	—	—	—	—
Hypertension	Cardiac disorders	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Viral sepsis	Infections and infestations	—	—	—	—
Tetraparesis	Nervous system disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Acute respiratory distress syndrome, Bacterial sepsis, Hepatic cytolysis, Anemia, Pulmonary embolism, Acute renal failure, Neutropenia, Cholestasis.

Data from ClinicalTrials.gov NCT04331808 adverse events section.

Sponsor's own description

The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.

Publications & conference data

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

1. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
   Merad M, Martin JC. · · 2020 · cited 1909× · PMID 32376901 · DOI 10.1038/s41577-020-0331-4
2. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic.
   Driggin E, Madhavan MV, Bikdeli B, Chuich T, et al · · 2020 · cited 1272× · PMID 32201335 · DOI 10.1016/j.jacc.2020.03.031
3. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial.
   Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, et al · · 2021 · cited 592× · PMID 33080017 · DOI 10.1001/jamainternmed.2020.6820
4. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts.
   Wang J, Jiang M, Chen X, Montaner LJ. · · 2020 · cited 551× · PMID 32534467 · DOI 10.1002/jlb.3covr0520-272r
5. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.
   WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, et al · · 2021 · cited 548× · PMID 34228774 · DOI 10.1001/jama.2021.11330
6. Immunopathology of Hyperinflammation in COVID-19.
   Gustine JN, Jones D. · · 2021 · cited 371× · PMID 32919977 · DOI 10.1016/j.ajpath.2020.08.009
7. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort.
   Pouletty M, Borocco C, Ouldali N, Caseris M, et al · · 2020 · cited 359× · PMID 32527868 · DOI 10.1136/annrheumdis-2020-217960
8. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection.
   Pons S, Fodil S, Azoulay E, Zafrani L. · · 2020 · cited 352× · PMID 32546188 · DOI 10.1186/s13054-020-03062-7