Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42564   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-001748-24
    Sponsor's Protocol Code Number:ImmCoVA
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-04-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2020-001748-24
    A.3Full title of the trial
    A multi-center, randomized, open-label 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.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A multi-center, randomized, open-label 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.
    A.3.2Name or abbreviated title of the trial where available
    The Immunomodulation-CoV Assessment (ImmCoVA) study.
    A.4.1Sponsor's protocol code numberImmCoVA
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKarolinska University Hospital
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKarolinska University Hospital, ME Infection diseases
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKarolinska University Hospital
    B.5.2Functional name of contact pointJonas Sundén-Cullberg
    B.5.3 Address:
    B.5.3.1Street AddressInfektionskliniken
    B.5.3.2Town/ cityStockholm
    B.5.3.3Post code141 86
    B.5.3.4CountrySweden
    B.5.4Telephone number0046858580000
    B.5.6E-mailjonas.sunden-cullberg@sll.se
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Kineret
    D.2.1.1.2Name of the Marketing Authorisation holderSwedish Orphan Biovitrum AB (publ)
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameKineret
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNANAKINRA
    D.3.9.1CAS number 143090-92-0
    D.3.9.4EV Substance CodeSUB05500MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name RoActemra
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRoActemra
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNtocilizumab
    D.3.9.1CAS number 375823-41-9
    D.3.9.3Other descriptive nameTOCILIZUMAB
    D.3.9.4EV Substance CodeSUB20313
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    COVID-19 infection in patients with respiratory distress.
    E.1.1.1Medical condition in easily understood language
    COVID-19 infection in patients with respiratory distress.
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to assess the effect of anakinra and tocilizumab on time to recovery in patients with COVID-19 and respiratory distress.
    E.2.2Secondary objectives of the trial
    Secondary objectives of the study are to assess the effect of anakinra and tocilizumab on mortality, need and length of intensive care, and also rate, magnitude and speed of clinical improvement including pulmonary function in patients with COVID-19 and respiratory distress.

    Exploratory objectives:
    The exploratory objective of the study is to assess the effect of anakinra and tocilizumab on selected biomarkers relevant for hyperinflammation and coagulation disturbances.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Age ≥18 years
    2) Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay < 3 days prior to screening
    3) SARS-CoV-2 infection with duration at least 7 days (as determined by onset of symptoms)
    4) 5 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 l liters/minute of Oxygen to maintain SpO2 at ≥93%.
    5) CRP > 70 mg/L with no non-SARS-Cov2 infections. Values measured up to 48 hours before inclusion are accepted.
    6) Ferritin > 500 µg/L. Values measured up to 48 hours before inclusion are accepted.
    7) At least two points on a scale of 0-3 where 1 point is awarded for each value of; lymphocytes < 1x 10(9)/L; D-dimer ≥ 0.5 mg/L and; Lactate Dehydrogenase ≥ 8 microkatal/L. The values do not have to be concurrently positive and may be up to 3 days old at inclusion.
    8) Ability to provide informed consent signed by study patient
    9) Willingness and ability to comply with study-related procedures/assessments
    10) In fertile females, willing to comply with effective contraceptive methods for up to 3 months after last dose of study drug. These may include birth control pills, surgical sterilization of patient or partner, intrauterine device or condoms, but not birth control pills which may increase risk of deep venous thrombosis during COVID infections. 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.

    E.4Principal exclusion criteria
    1) Pregnancy or breast feeding.
    2) Ongoing or completed mechanical ventilation.
    3) In the opinion of the investigator, unlikely to survive for >48 hours from screening.
    4) In the opinion of the investigator, expected overall survival due to other comorbidities less than 3 months.
    5) Severe renal dysfunction eGFR < 30 ml/min.
    6) 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.
    7) Uncontrolled hypertension Systolic BP >180 mm Hg, Diastolic BP > 110 mm Hg
    8) History of hypersensitivity to the study drugs
    9) 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
    10) 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
    11) Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents
    12) Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. Ongoing acute treatment for COVID-19 with any peroral or iv steroid is permitted for up to five days before inclusion. Chronic or acute treatment with inhaled steroids is also permitted.
    13) History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis
    14) Acute systemic infection; verified by blood cultures systemic bacterial infection, systemic fungi-infection or prosthesis-related infection
    15) History of stem-cell or solid organ transplantation
    16) Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
    17) Diagnosis of, or suspicion of HIV infection, acute hepatitis A and/or chronic hepatitis B and/or C
    18) Previous history of gastrointestinal ulceration or diverticulitis.
    19) Patients who have received immunosuppressive antibody therapy within the past 3 months, including intravenous immunoglobulin or plans to receive during the study period
    20) Participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. The use of remdesivir is permitted.
    21) Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study



    E.5 End points
    E.5.1Primary end point(s)
    1. Time to recovery [ Time Frame: Day 1 through Day 29 ]
    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

    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 1-29.
    E.5.2Secondary end point(s)
    1. Mortality [ Time Frame: Up to day 29 ]
    2. Number of Days on mechanical ventilation [ Time Frame: Up to day 29 ]
    3. Number of days of supplemental oxygen use [ Time Frame: Up to day 29 ]
    4. Number of patients requiring initiation of mechanical ventilation [ Time Frame: Up to day 29 ]
    5. Time to improvement in oxygenation for at least 48 hours [ Time Frame: Up to day 29 ]
    Definition of improvement in oxygenation: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
    6. Mean change in the 8-point ordinal scale from baseline and nadir at days 8 and 15
    7. Proportion of patients on level e-h on the 8-point ordinal scale at day 15
    8. Time to improvement in one category from baseline using the 8-point ordinal scale [ Time Frame: Up to day 29 ]
    9. Mean change in SOFA score from baseline until days 5, 10 and 15
    10. Time to resolution of fever for at least 48 hours [ Time Frame: Up to day 29 ]
    Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)
    11. Time to improvement of three points from baseline in the National Early Warning Score 2 (NEWS2) scoring system [ Time Frame: Up to day 29 ]
    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
    12. Time to score of <2 maintained for 24 hours in NEWS2 scoring system [ Time Frame: Up to day 29 ] NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
    13. Mean change in NEWS2 scoring system from baseline until days 5, 10 and 15
    14. Number of days with fever from baseline. Based on highest measured daily body temperature [ Time Frame: Up to day 29 ] Defined as >36.6°C (axilla), >37.2°C (oral) or >37.8°C (rectal or tympanic)
    15. Number of days from baseline of resting respiratory rate >24 breaths/min. Based on highest respiratory rate measured between 06.00 and 09.00 each day [ Time Frame: Up to day 29 ]
    16. Time to saturation ≥94% on room air [ Time Frame: Up to day 29 ]
    17. Cumulative dose of steroids; equivalent to betamethasone dosage (mg) [ Time Frame: From start of steroid treatment for Covid-19 up to day 29 ]
    18. Cumulative dose of steroids during the study; equivalent to betamethasone dosage (mg) [ Time Frame: From day 1 up to day 29 ]
    19. Incidence of serious adverse events [ Time Frame: Up to day 60 ]
    20. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection [ Time Frame: Up to day 29 ]
    21. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with grade 4 neutropenia [ Time Frame: Up to day 60 ]
    22. Incidence of hypersensitivity reactions [ Time Frame: Up to day 29 ]
    23. Incidence of infusion reactions [ Time Frame: Up to day 29 ]
    24. Number of ventilator free days in the first 28 days [ Time Frame: Baseline to day 29 ]
    25. Number of patients requiring non-invasive ventilation [ Time Frame: Up to day 29 ]
    26. Number of patients requiring the use of high flow nasal cannula [ Time Frame: Up to day 29 ]
    27. Number of patients requiring ECMO [ Time Frame: Up to day 29 ]
    28. Number of patients that have been admitted into an intensive care unit (ICU) [ Time Frame: Up to day 29 ]
    29. Number of patients that have been admitted into a High Dependency Unit (“Intermediärvårdsavdelning”) [ Time Frame: Up to day 29 ]
    30. Number of days admitted into a High Dependency Unit (“Intermediärvårdsavdelning”) or intensive care unit (ICU) [ Time Frame: Up to day 29 ]
    31. Number of days of hospitalization in survivors [ Time Frame: Up to day 29 ]
    32. Number of patients discharged to institution other than normal domicile.
    33. Number of deaths due to any cause [ Time Frame: Up to day 60 ]

    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluations done up to day 29 except for;
    - item 6, 7, 9, 13 up to day 15
    - item 19, 21, 33 up to day 60
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    SOC, i.e Oxygen suppl. (SpO2 ≥93 %), antipyretic treatment , thrombosis prophylaxis
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will be followed according to SOC by the treating physician and as clinically indicated.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-05-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-05-17
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA