Anakinra, COVID-19, Cytokine Storm

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-31

Study Completion Date

2022-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The clinical syndrome associated with infection of the Coronavirus Disease 2019 (COVID-19) is notable for its variable clinical expression. Infection and transmission of the virus by asymptomatic individuals have been noted and represent one end of the clinical spectrum, while multi-organ failure, particularly pulmonary failure, and death represent the most severe end of the clinical spectrum. In a recent study published from the investigator's institution about the first 393 patients with COVID-19, 77.1% had a fever, a mechanism driven by IL-1. This suggests that there may be an excess release of IL-1 present.

Cytokine storm syndrome (CSS) has been observed in patients with COVID-19 and has been proposed to contribute to the acute pulmonary failure that occurs. In distinct clinical settings, macrophage activation syndrome, elevated levels of pro-inflammatory cytokines, including IL-1, IL-6, and others, as well as elevations in laboratory indicators, including ferritin, CRP, d-dimer, and lymphopenia, have been observed. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Anakinra, a recombinant IL-1 receptor antagonist, has shown promise in treating CSS. It inhibits both IL-1-alpha and IL-1-beta. It is an FDA approved medication used in rheumatoid arthritis (RA) and Cryopyrin-Associated Periodic Syndromes (CAPS). Anakinra's ability to inhibit both IL-1 subtypes and short half-life makes it favorable to some experts. In the investigator's case-series, using anakinra in patients with COVID-19 showed promising in preventing the need for mechanical ventilation, and mortality subsequently.

This study will determine the efficacy of anakinra, an interleukin (IL) -1 receptor blocker, in reducing the need for mechanical ventilation and/or 28-day mortality among patients with COVID-19 who have features of CSS and severe respiratory failure. The investigators will test the hypothesis that the proportion of subjects with COVID-19, features of CSS, and severe respiratory failure (World Health Organization (WHO) category 4 or 5) alive and without having required mechanical ventilation at day 28 from randomization will be 18% higher among those that receive anakinra compared to those that receive a placebo. A secondary hypothesis is that the number of subjects alive at 60-days will be higher amongst those who receive anakinra compared to those who receive a placebo.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Anakinra for COVID-19 Respiratory Symptoms

NCT04364009

COVID-19 Infection ANAKINRA Treatment Optimized Standard of Care (oSOC)

TERMINATED PHASE3

Convalescent Plasma for Treatment of COVID-19

NCT04649879

Covid19

COMPLETED PHASE2/PHASE3

Anakinra in the Management of COVID-19 Infection

NCT04643678

Covid19 Pneumonia Cytokine Release Syndrome +2 more

COMPLETED PHASE2/PHASE3

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

NCT04341584

Corona Virus Infection

COMPLETED PHASE2

Convalescent Plasma as Treatment for Acute Coronavirus Disease (COVID-19)

NCT04390178

COVID-19

COMPLETED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Covid19 Cytokine Storm Mechanical Ventilation Complication

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study is a phase II double-blind, placebo-controlled, multicentered trial. Patients in the intervention arm will receive anakinra IV (N=85) 4 times a day for 7 days. The placebo arm will receive normal saline IV (N=85) 4 times a day for 7 days. The investigators will follow up with patients for up to 60 days.

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Anakinra IV

Patients in the intervention arm will receive anakinra IV (N=85) 4 times a day for 7 days. The investigator will follow up with patients for up to 60 days.

Group Type EXPERIMENTAL

Anakinra

Intervention Type DRUG

100 mg of Anakinra will be mixed with 100 mL of 0.9% saline solution for IV administration.

Normal Saline IV

Patients in the placebo arm will receive normal saline IV (N=85) 4 times a day for 7 days. The investigator will follow up with patients for up to 60 days.

Group Type PLACEBO_COMPARATOR

0.9% Saline

Intervention Type DRUG

The placebo preparation will consist of a 100 mL of 0.9% saline solution without the addition of anakinra.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Anakinra

100 mg of Anakinra will be mixed with 100 mL of 0.9% saline solution for IV administration.

Intervention Type DRUG

0.9% Saline

The placebo preparation will consist of a 100 mL of 0.9% saline solution without the addition of anakinra.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Anakinra IV Saline IV

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. An IRB approved written Informed Consent Form (ICF) is signed and dated by the subject or legal representative.
2. The subject or legal representative must be considered capable of understanding the study procedures to provide consent for participation according to the judgment of the Investigator.
3. Molecular diagnosis of SARS-CoV-2 infection within 14 days of screening assessment.
4. Radiographic evidence of pneumonia by either chest X-ray or computerized tomography (CT) scan of the chest if collected as part of the standard of care.
5. Age between 18-89 years of age at the screening visit.

1. Fever documented ≥ 38 ˚C (from the time of admission to the hospital), or historical fever (patient-reported).

AND
2. Respiratory failure defined as:

i.Requiring supplemental O2 of ≥ 4 L nasal cannula or more to maintain an O2 saturation ≥ 92%, within 36 hours of the requirement for that level of O2.24 (Individuals on continuous positive airway pressure (CPAP) or high flow nasal cannula will be allowed)

AND

c. Ferritin \> 1000 ng/mL at the time of screening.
7. Not requiring mechanical ventilation or ECMO at Screening and Baseline Assessments.
8. ANC must be \> 1 x 10\^9/L before randomization
9. Platelet count must be ≥ 50 x 10\^9/L before randomization.
10. Negative pregnancy test before randomization (women of childbearing age only).
11. GFR ≥ 30 mL/min based on the Modification of Diet in Renal Disease equation.
12. Subjects participating in studies for convalescent plasma or anticoagulation protocol for COVID-19 will be included as long as these are also open-label.

Exclusion Criteria

1. The subject is not expected to survive for more than 48 hours from screening, in the opinion of the investigator.
2. Subjects participating in studies for COVID-19 with immunomodulating drugs, will be excluded. See Section 4.3.1 for drugs or investigational drugs for COVID-19 not allowed in this study.
3. Subject is currently participating in another study with an investigational drug. Participation in observational studies is allowed.
4. Known hypersensitivity to anakinra or E. coli derived proteins.
5. Existence of other evidence that can explain pneumonia including but not limited to: Influenza A virus, Influenza B virus, bacterial pneumonia, fungal pneumonia, or mycobacterial infection.
6. Known or suspected active TB including those incompletely treated, or known latent TB not adequately treated.

1. Known or suspected active TB including those incompletely treated.
2. Exclude patients with known latent TB including those incompletely treated (patient reported).
7. Known human immunodeficiency virus (HIV) infection.
8. Culture confirmed active bacterial infection requiring antibiotic therapy.
9. Subjects who are: do not intubate (DNI) and/or do not resuscitate (DNR) will not be allowed in the study.
10. Subjects already on mechanical ventilation or on extracorporeal membrane oxygenation (ECMO).
11. Subjects with Eastern Co-operative Oncology Group (ECOG)/WHO system score ≥ 3 before their hospital admission.
12. Subjects with past or current lymphoproliferative disorder requiring current medical treatment (e.g., chemotherapy, radiotherapy) for these conditions.
13. Current or past history of a solid tumor including breast or prostate cancer requiring current medical treatment.
14. Subjects receiving other immunosuppressants.
15. Use of the following medications within 6 months of randomization:

1. Tumor necrosis factor inhibitors
2. Chronic IL-1 use such as canakinumab or anakinra.
3. IL-6 inhibitors: Use of any IL-6
4. Janus kinase inhibitors
5. Bruton's tyrosine kinase inhibitor
6. C-C Chemokine receptor type 5
7. Disease-modifying anti-rheumatic drugs (DMARD), which include cyclosporine, tacrolimus, cyclophosphamide, mycophenolic acid, mycophenolate, penicillamine, azathioprine, methotrexate.
8. Rituximab and abatacept

Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No