CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection (CORIMUNO-ANA)

CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection, Nested In The CORIMUNO-19

The overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the CORIMUNO-19 cohort. Anakinra 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 Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: Anakinra

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France
    • Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort
2. Patients with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion)

3. Patients belonging to one of the 2 following groups:

   • Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No non invasive ventilation or High flow
   • Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR non invasive ventilation OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order

Exclusion Criteria:

• Patients with exclusion criteria to the CORIMUNO-19 cohort.
• Known hypersensitivity to Anakinra 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:

  • Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
  • Haemoglobin level: no limitation
  • Platelets (PLT) < 50 G /L
  • SGOT or SGPT > 5N
  • Severe renal insufficiency with Glomerular filtration rate < 30 ml / mn

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANAKINRA -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline); Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter	Drug: Anakinra; Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
No Intervention: Standard of care -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline)
Experimental: ANAKINRA -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline); Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter	Drug: Anakinra; Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
No Intervention: Standard of care -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (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 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.	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 (percentage) 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
Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5)	Percentage of patients with a decrease of WHO score of at least 1 point at day 4	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WHO Clinical Progression Scale	WHO clinical 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 Non invasive Ventilation 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, 7, 14, 28 days
Percentage of Participants Surviving (Overall Survival)	Percentage of participants surviving at 14, 28 and 90 days	14, 28 and 90 days
Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)	28-day Ventilator Free-days	28 days
PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)	Evolution of PaO2/FiO2 ratio	day 1 to day 14
Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency	Time to oxygen supply independency	28 and 90 days
Cumulative Incidence (Percentage of Participants) of Discharge From Hospital	Time to discharge from hospital	28 days
Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)	Time to discharge from Intensive Care Unit	28 and 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Xavier Mariette, MD, PhD, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris

Publications and helpful links

General Publications

• CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med. 2021 Mar;9(3):295-304. doi: 10.1016/S2213-2600(20)30556-7. Epub 2021 Jan 22.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): May 10, 2020
• Study Completion (Actual): July 25, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 7, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; RNA Virus Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; Infections; Communicable Diseases; Coronavirus Infections; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: APHP200375-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No