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

NCT04331808 | Completed Phase 2 Results DMC

• 1 other identifier: APHP200375-1
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Corona Virus Infection

Outcome Measures

Primary Outcomes (4)

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

  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 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: 10

  4 days

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

  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.

  Day 1 to Day 14

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

  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 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2\<150 AND vasopressors (norepinephrine \>0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

  4 days

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

  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.

  Day 1 to Day 14

Secondary Outcomes (7)

• Percentage of Participants Surviving (Overall Survival)

  14, 28 and 90 days

• WHO Progression Scale

  4, 7 and 14 days

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

  28 days

• Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency

  Day 28, 90

• Cumulative Incidence (Percentage of Participants) of Discharge From Hospital

  28, 90 days

Study Arms (4)

TOCILIZUMAB -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline)

EXPERIMENTAL

Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale

Drug: Tocilizumab

Standard of care -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline)

NO INTERVENTION

Usual care was provided at the discretion of the clinicians

TOCILIZUMAB -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline)

EXPERIMENTAL

Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale

Drug: Tocilizumab

Standard of care -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline)

NO INTERVENTION

Usual care was provided at the discretion of the clinicians

Interventions

Tocilizumab DRUG

Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg)

TOCILIZUMAB -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline); TOCILIZUMAB -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients included in the CORIMUNO-19 cohort
• Patients belonging to one of the 2 following groups:
• Group 1: Cases meeting all of the following criteria
• Requiring more than 3L/min of oxygen
• OMS/WHO progression scale = 5
• No Non Invasive Ventilation or High flow
• Group 2: Cases meeting all of the following criteria
• Respiratory failure AND (requiring mechanical ventilation OR Non Invasive Ventilation OR High flow)
• WHO progression scale \>=6
• No do-not-resuscitate order (DNR order)

You may not qualify if:

• Known hypersensitivity to Tocilizumab or to any of their excipients.
• Pregnancy
• Current documented bacterial infection
• Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
• Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
• Haemoglobin level: no limitation
• Platelets (PLT) \< 50 G /L
• SGOT or SGPT \> 5N

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (8)

APHP- Hopital Tenon

Paris, 75012, France

Location

APHP - Beaujon

Paris, France

Location

APHP - Bichat

Paris, France

Location

APHP - Hopital Necker

Paris, France

Location

APHP - Pitié Salpêtrière

Paris, France

Location

APHP - Saint Louis

Paris, France

Location

CHU Strasbourg

Strasbourg, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (6)

• Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):32-40. doi: 10.1001/jamainternmed.2020.6820.

  PMID: 33080017 RESULT

• Mariette X, Hermine O, Tharaux PL, Resche-Rigon M, Steg PG, Porcher R, Ravaud P. Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19: A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial. JAMA Intern Med. 2021 Sep 1;181(9):1241-1243. doi: 10.1001/jamainternmed.2021.2209.

  PMID: 34028504 RESULT

• Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. Eur Respir J. 2022 Aug 10;60(2):2102523. doi: 10.1183/13993003.02523-2021. Print 2022 Aug.

  PMID: 35115337 RESULT

• Lenoir O, Morin F, Walter-Petrich A, Resmini L, Zaidan M, Mahtal N, Ferlicot S, Puelles VG, Wanner N, Dang J, d'Izarny-Gargas T, Biermann J, Izar B, Baron S, Terrier B, Massy ZA, Essig M, Couturier A, May O, Belenfant X, Buob D, Brocheriou I, Izzedine H, Lombardi Y, Francois H, Moktefi A, Audard V, Sannier A, Daugas E, Jamme M, Henry G, Le Monnier de Gouville I, Marie C, Homyrda L, Verstuyft C, Tubiana S, Kafif O, Piquard V, Dougados M, Huber TB, Livrozet M, Hulot JS, Laouenan C, Ghosn J, Mentre F, Karras A, Yazdanpanah Y, Porcher R, Ravaud P, Caillat-Zucman S, Mariette X, Hermine O, Resche-Rigon M, Tharaux PL; CORIMUNO-19 collaborative group. Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death. JCI Insight. 2026 Jan 23;11(2):e198244. doi: 10.1172/jci.insight.198244. eCollection 2026 Jan 23.

  PMID: 41574613 DERIVED

• Joly C, Desjardins D, Porcher R, Pere H, Bruneau T, Zhang Q, Bastard P, Cobat A, Resmini L, Lenoir O, Savale L, Lecuroux C, Verstuyft C, Roque-Afonso AM, Veyer D, Baron G, Resche-Rigon M, Ravaud P, Casanova JL, Le Grand R, Hermine O, Tharaux PL, Mariette X. More rapid blood interferon alpha2 decline in fatal versus surviving COVID-19 patients. Front Immunol. 2023 Nov 21;14:1250214. doi: 10.3389/fimmu.2023.1250214. eCollection 2023.

  PMID: 38077399 DERIVED

• Tleyjeh IM. The Misleading "Pooled Effect Estimate" of Crude Data from Observational Studies at Critical Risk of Bias: The Case of Tocilizumab in Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2021 Jun 15;72(12):e1154-e1155. doi: 10.1093/cid/ciaa1735. No abstract available.

  PMID: 33201228 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Dr Raphael Porcher
• Organization: Hopital Hotel Dieu (AP-HP)

raphael.porcher@aphp.fr

+33 (0)1.42.34.89.87

Study Officials

• Xavier MARIETTE, MD PhD

  Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 2, 2020
• Study Start: March 30, 2020
• Primary Completion: May 4, 2020
• Study Completion: November 9, 2020
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (8)