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    Summary
    EudraCT Number:2020-003278-37
    Sponsor's Protocol Code Number:INSIGHT-014-ACTIV-3
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-12-24
    Trial results View 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 number2020-003278-37
    A.3Full title of the trial
    A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients with COVID-19
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Therapeutics for Inpatients with COVID-19 (TICO)
    A.3.2Name or abbreviated title of the trial where available
    Therapeutics for Inpatients with COVID-19 (TICO)
    A.4.1Sponsor's protocol code numberINSIGHT-014-ACTIV-3
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04501978
    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 SponsorRegents of the University of Minesota
    B.1.3.4CountryUnited States
    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 supportNational Institutes of Health - NIH
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportUniversity of Minnesota
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHIP - Rigshospitalet, University of Copenhagen
    B.5.2Functional name of contact pointJens Lundgren
    B.5.3 Address:
    B.5.3.1Street AddressBlegdamsvej 9
    B.5.3.2Town/ cityCopenhagen Ø
    B.5.3.3Post code2100
    B.5.3.4CountryDenmark
    B.5.4Telephone number+453545 5757
    B.5.5Fax number+453545 5758
    B.5.6E-mailjens.lundgren@regionh.dk
    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 No
    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.3.2Product code AZD7442
    D.3.4Pharmaceutical form 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.3.9.2Current sponsor codeAZD7442
    D.3.9.3Other descriptive nameHUMAN IMMUNOGLOBULIN G
    D.3.9.4EV Substance CodeSUB127300
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 No
    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 No
    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 nameEnsovibep
    D.3.2Product code MP0420
    D.3.4Pharmaceutical form 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 INNEnsovibep
    D.3.9.2Current sponsor codeMP0420
    D.3.9.3Other descriptive nameDARPin targeting three different epitopes of SARS-CoV-2 receptor-binding domain
    D.3.9.4EV Substance CodeSUB218142
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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) No
    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 No
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects infected with SARS-CoV-2, admitted to the hospital due to COVID-19.
    E.1.1.1Medical condition in easily understood language
    Infection with Coronavirus SARS-CoV-2/COVID-19 that leads to hospitalization
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level PT
    E.1.2Classification code 10084460
    E.1.2Term COVID-19 treatment
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10084268
    E.1.2Term COVID-19
    E.1.2System Organ Class 10021881 - Infections and infestations
    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 of this protocol is to determine whether investigational agents, initially focusing on those that are aimed at enhancing the host immune response to SARS-CoV-2 infection are safe and superior to control (e.g., placebo) when given with SOC for the primary endpoint of time to sustained recovery evaluated up to 90 days after randomization.
    SOC may be modified (updated based on data from this or other trials) during the course of evaluating different investigational agents with this master protocol.
    E.2.2Secondary objectives of the trial
    Two key secondary objectives are to compare each investigational agent with control for all-cause mortality and a composite outcome which considers both time to sustained recovery and mortality.
    Other secondary objectives are to compare each investigational agent with control for the secondary outcomes stated in section 4 in the protocol
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥ 18 years

    2. Informed consent by the patient or the patient’s legally-authorized representative (LAR)*

    3. SARS-CoV-2 infection, documented by a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator. (For non-NAT tests only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non-NAT tests will be maintained.)

    4. Duration of symptoms attributable to COVID-19 ≤ 12 days per the responsible investigator

    5. Requiring admission for inpatient hospital acute medical care for clinical manifestations of COVID-19, per the responsible investigator, and NOT for purely public health or quarantine purposes
    E.4Principal exclusion criteria
    1. Prior receipt of
    • Any SARS-CoV-2 hIVIG, convalescent plasma from a person who recovered from COVID-19 or
    • SARS-CoV-2 nMAb at any time prior to hospitalization

    2. Not willing to abstain from participation in other COVID-19 treatment trials until after Day 5 (with thie approval of study leadership enrollment before or on Day 5 is permitted for trials comparing different approaches for implementing SOC interventions that are recommended in a)i))(1)(a)(i)Appendix I

    3. In the opinion of the responsible investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol specified assessments

    4. Expected inability to participate in study procedures

    5. Women of child-bearing potential who are not already pregnant at study entry and who are unwilling acknowledge the strong advice to abstain from sexual intercourse with men or practice appropriate contraception through 18 month of the study

    6. Men who are unwilling acknowledge the strong advice to to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through 18 month of the study

    Prior to the initial futility assessment for an investigational agent, the follwoing two additional exclusions (7 and 8) which define disease severity stratum 2 apply:
    7. Presence at enrollment of any of the following:
    a. stroke
    b. meningitis
    c. encephalitis
    d. myelitis
    e. myocardial infarction
    f. myocarditis
    g. pericarditis
    h. symptomatic CHF (NYHA class III-IV)
    i. arterial or deep venous thrombosis or pulmonary embolism

    8. Current requirement for any of the following:
    a. invasive mechanical ventilation
    b. ECMO
    c. mechanical circulatory support
    d. vasopressor therapy
    e. commencement of renal replacement therapy at this admission (i.e. not patients on chronic renal replacement therapy).

    Additional exclusion citeria according to "Protocol amendment for Sweden, No. 2"

    9. Pregnant and nursing women must be excluded.

    10. AZD7442 are contraindicated in participants who have shown hypersensitivity to the active substance or any of the excipients or to other humanised mAbs.

    11. For MP0420 there is currently no clinical experience, consequently no specific contraindications have been identified.

    Exclusions that may be appropriate for an investigational agent studied are referenced in the relevant appendix (H) for the investigational agent. The contraindications for use of components of SOC are outlined in Appendix I and in the PIM
    E.5 End points
    E.5.1Primary end point(s)
    Ordinal Outcomes for Early Futility Assessments:
    Two ordinal outcomes will be used to assess futility after approximately 300 patientes have been enrolled. Both outcomes are assessed 5 days after randomization (Day 5); the participant’s highest (i.e. most severe) observed score on Day 5 is used.
    The first ordinal outcome, referred to as the “pulmonary” ordinal outcome, is primarily defined based on oxygen requirements.
    The second ordinal outcome, referred to as “pulmonary+,” also assessed at Day 5, captures extra-pulmonary complications as well as respiratory dysfunction.

    Primary and Secondary Outcomes to Evaluate Efficacy and Safety:
    The primary endpoint is time from randomization to sustained recovery, defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
    Home is defined as the level of residence or facility where the participant was residing prior to hospital admission leading to enrollment in this protocol.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary outcome is assessed during 90 days of follow-up, which is longer than for other trials for COVID-19, which are typically 28 days. The longer follow-up will allow better ascertainment of recovery from the longer-term consequences of the underlying disease, and hence the efficacy of the investigational agent. This is likely to be particularly true for patients who experience extra-pulmonary disease in conjunction with their COVID-19, and for patients enrolled while receiving care for life-threatening organ failure.
    E.5.2Secondary end point(s)
    Several secondary efficacy endpoints will be assessed. These endpoints will be assessed for all participants enrolled:
    1. All-cause mortality through 90 days of follow-up
    2. Composite of time to sustained recovery and mortality through 90 days of follow-up
    3. Time to discharge for the initial hospitalization
    4. Days alive outside of a short-term acute care hospital up to day 90
    5. Ordinal outcomes, pulmonary+ and pulmonary, on Days 1-7, and pulmonary ordinal outcome on Days 14 and 28
    6. Clinical organ failure or serious infection defined by development of any one or more of the following clinical events through Day 28:
    a. Respiratory dysfunction
    b. Cardiac and vascular dysfunction
    c. Renal dysfunction
    d. Hepatic dysfunction
    e. Neurological dysfunction
    f. Haematological dysfunction
    g. Serious infection
    7. A composite of death, clinical organ failure or serious infection (see above)
    8. Outcomes assessed in other treatment trials of COVID-19 for hospitalized participants in order to facilitate cross-trial comparisons and overviews (e.g. 6- , 7-, and 8-category ordinal scales assessed at Days 1-7, 14 and 28; time to improvement in 1 or 2 categories of ordinal scale; time to best 3 categories of ordinal scale, and binary outcomes defined by improvement or worsening based on other ordinal outcomes)
    9. A composite of cardiovascular events (outcomes listed above in items 6) and thormboembolic events
    10. Safety and tolerability as measured by:
    a. A composite of grade 3 and 4 clinical adverse events, SAEs, clinical organ failure or serious infections (see item 6) or death through Day 5 (primary safety endpoint) and through Day 28
    b. Infusion-related reactions of any severity and percentage of participants for whom the infusion was interrupted or stopped prior to completion
    c. A composite of SAEs, clinical organ failure or serious infections (see item 6) or death through Day 90
    d. Adverse events of any grade through Day 7
    e. Prevalence of adverse events of any grade at day 14 and day 28
    f. A composite of hospitalisations or death through 12 month
    11. Change in antibody profile, overall titers of antibodies and neutralizing antibody levels from baseline to Days 1, 3, 5 and 28 and 90
    12. Outcomse that consider home use of supplemental oxygen above pre-morbid oxygen use for sensitivity analyses fo rthe primary outcome:
    a. Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14 day period
    b. Alive at home for an uninterrupted 14 day period and no use of continuous supplemental oxygen at the end of the 14 day time period
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints for the measurements are described in connection with the individual secondary endpoints.
    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) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Adaptive
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Brazil
    Georgia
    Mexico
    Peru
    Singapore
    Uganda
    United States
    Belgium
    Denmark
    France
    Germany
    Greece
    Poland
    Portugal
    Spain
    Sweden
    Switzerland
    United Kingdom
    Argentina
    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 years2
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    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: 500
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 500
    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 Yes
    F.3.3.4Nursing women Yes
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Informed consent given by the patient’s legally-authorized representative will be used in counties where this is allowed. Participants who subsequently regain decision-making capacity will be asked to give consent for continuing participation.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 1000
    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)
    None
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation INSIGHT (International Network for Strategic Initiatives in Global HIV Trials)
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-02-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-12
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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