A Study in Patients With COVID-19 and Respiratory Distress Not Requiring Mechanical Ventilation, to Compare Standard-of-care With Anakinra and Tocilizumab Treatment The Immunomodulation-CoV Assessment (ImmCoVA) Study

NCT04412291 | Unknown Phase 2 DMC

• 1 other identifier: 2020-001748-24
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed as a randomized, controlled, multi-center open-label trial to compare standard-of-care (SOC) treatment with SOC + anakinra or SOC + tocilizumab treatment in hospitalized adult subjects who are diagnosed with severe COVID 19. Arm A: Standard-of-care Treatment (SOC) Arm B: Anakinra + SOC Arm C: Tocilizumab + SOC. All subjects will be treated with standard-of-care treatment. Arms B and C will also receive broad spectrum antibiotics initiated before or latest 24 hours after initiation of treatment with study drug. The primary follow-up period of the study is 29 days.

Conditions

Covid-19

Keywords

Coronavirus 2; SARS-CoV-2; Anakinra; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Time to recovery

  Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 1; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities. 1 LMWH-injections (Fragmin, Innohep) do not count as medical care

  Day 1 through Day 29

Secondary Outcomes (33)

• Mortality

  Up to day 29

• Number of Days on mechanical ventilation

  Up to day 29

• Number of days of supplemental oxygen use

  Up to day 29

• Number of patients requiring initiation of mechanical ventilation

  Up to day 29

• Time to improvement in oxygenation for at least 48 hours

  Up to day 29

Study Arms (3)

Standard-of-care Treatment (SOC)

ACTIVE COMPARATOR

SOC according to local recommendations at the Karolinska University Hospital: Oxygen supplementation so to achieve SpO2\>93%. Thrombosis prophylaxis (Fragmin or Innohep or Klexane or new oral anticoagulants incl. dabigatran, apixaban or rivaroxaban). Steroids (Betapred)

Drug: Standard-of-care treatment

Anakinra + SOC

ACTIVE COMPARATOR

Anakinra: A total dose of 400mg per day (divided in 4 doses of 100 mg iv every 6 hours) for 7 days. SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2\>93%. Thrombosis prophylaxis (Fragmin or Innohep) Steroids (Betapred) Prophylactic broad spectrum antibiotics for seven days..

Drug: Anakinra Prefilled Syringe; Drug: Standard-of-care treatment

Tocilizumab + SOC.

ACTIVE COMPARATOR

Tocilizumab: 8mg/kg for a single infusion iv up to max 800 mg. If no clinical response is obtained, another dose of 8mg/kg may be administered after earliest 2 days SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2\>93%. Thrombosis prophylaxis (Fragmin or Innohep) Steroids (Betapred) Prophylactic broad spectrum antibiotics for seven days.

Drug: Tocilizumab Prefilled Syringe; Drug: Standard-of-care treatment

Interventions

Anakinra Prefilled Syringe DRUG

A total dose of 400mg per day (divided in 4 doses of 100 mg iv every 6 hours) for 7 days.

Anakinra + SOC

Tocilizumab Prefilled Syringe DRUG

8mg/kg for a single infusion iv up to max 800 mg. If no clinical response is obtained, another dose of 8mg/kg may be administered after earliest 2 days after inclusion with the following condition: The clinical symptoms are worsened (as assessed by decreasing PaO2/FiO2 and/or need of increased ventilatory support such as NIV, HFNC or mechanical ventilation).

Tocilizumab + SOC.

Standard-of-care treatment DRUG

SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2\>93%. Thrombosis prophylaxis (Fragmin or Innohep and Klexane® or new oral anticoagulants including dabigatran, apixaban or rivaroxaban). Steroids (Betapred 6 mg po) Broad spectrum antibiotics (only in arm B and C)

Also known as: Oxygen supplementation, Thrombosis prophylaxis, Steroids, Antibiotics

Anakinra + SOC; Standard-of-care Treatment (SOC); Tocilizumab + SOC.

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay \< 7 days prior to screening
• SARS-CoV-2 infection with duration at least 7 days (i e may be included on day 7) as determined by onset of symptoms (defined as day 1)
• liters/minute of Oxygen for at least 8 hours to maintain SpO2 at ≥93%. A shorter duration is also accepted if presentation is acute, and the patient needs more than 10 liters/minute of Oxygen, or high flow nasal cannula or non-invasive ventilation, to maintain SpO2 at ≥93%..
• Ability to provide informed consent signed by study patient
• Willingness and ability to comply with study-related procedures/assessments
• In fertile females, willing to comply with effective contraceptive methods for up to 3 months after last dose of study drug. These may include surgical sterilization of patient or partner, intrauterine device or condoms. Gestagen-only birth control pills (mini-pills), which do not increase the risk of deep venous thrombosis, may also be used. Non-fertile woman is defined as more than 12 months of amenorrhea without an alternative medical cause or, in case of ambiguities, an FSH level in the postmenopausal range.

You may not qualify if:

• Pregnancy or breast feeding.
• Ongoing or completed mechanical ventilation.
• In the opinion of the investigator, unlikely to survive for \>48 hours from screening.
• In the opinion of the investigator, expected overall survival due to other comorbidities less than 3 months.
• Severe renal dysfunction eGFR \< 30 ml/min.
• Medical history including chronic liver disease with inflammation, fibrosis or cirrhosis including underlying diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis, alcoholic liver disease, autoimmune liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis, or carcinoma.
• Uncontrolled hypertension Systolic BP \>180 mm Hg, Diastolic BP \> 110 mm Hg.
• History of hypersensitivity to the study drugs
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2 x 109/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN), platelets \<100 x 109/L
• Treatment with anakinra, anti-IL 6, anti-IL-6R antagonists, Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents
• History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis
• Acute systemic infection; verified by blood cultures systemic bacterial infection, systemic fungi-infection or prosthesis-related infection
• History of stem-cell or solid organ transplantation
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Karolinska University Hospital

Huddinge, Stockholm County, 141 86, Sweden

RECRUITING

Related Publications (1)

• Sunden-Cullberg J, Chen P, Habel H, Skorup P, Janols H, Rasmuson J, Niward K, Ostholm Balkhed A, Chatzidionysiou K, Asgeirsson H, Blennow O, Parke A, Svensson AK, Muvva JR, Ljunggren HG; Karolinska KI/K COVID-19 Treatment Working Group; Horne AC, Aden U, Henter JI, Sonnerborg A, Vesterbacka J, Nowak P, Lampa J. Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial. PLoS One. 2023 Dec 29;18(12):e0295838. doi: 10.1371/journal.pone.0295838. eCollection 2023.

  PMID: 38157348 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Steroids; Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• jonas Sundén-Cullberg, MD PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Investigator Jonas Sundén-Cullberg, MD PhD

CONTACT

+46-8-58580000; Jonas.sunden-cullberg@sll.se

Jon Lampa, MD PhD

CONTACT

+46-8-58580000; jon.lampa@sll.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 2, 2020
• Study Start: June 11, 2020
• Primary Completion: March 1, 2021
• Study Completion: June 1, 2021
• Last Updated: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

SE (1)