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

NCT04341584 | Completed Phase 2 Results DMC

• 1 other identifier: APHP200375-5
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Corona Virus Infection

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• WHO Clinical Progression Scale

  4, 7, 14, 28 days

• Percentage of Participants Surviving (Overall Survival)

  14, 28 and 90 days

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

  28 days

• PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)

  day 1 to day 14

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

  28 and 90 days

Study Arms (4)

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

EXPERIMENTAL

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

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

NO INTERVENTION

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

EXPERIMENTAL

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

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

NO INTERVENTION

Interventions

Anakinra DRUG

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

ANAKINRA -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline); ANAKINRA -- 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 with C-reactive protein level (CRP) \> 25 mg / L the day or the day before the infusion)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris

Le Kremlin-Bicêtre, France

Location

Related Publications (2)

• 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.

  PMID: 33493450 RESULT

• 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

MeSH Terms

Conditions

Coronavirus Infections

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

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: April 7, 2020
• First Posted: April 10, 2020
• Study Start: April 8, 2020
• Primary Completion: May 10, 2020
• Study Completion: July 25, 2020
• Last Updated: June 6, 2025
• Results First Posted: June 6, 2025

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)