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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2021-001663-24
    Sponsor's Protocol Code Number:INSIGHT-012-OTAC
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-07-25
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2021-001663-24
    A.3Full title of the trial
    An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Outpatients in Early Stages of COVID-19
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Same as above
    A.3.2Name or abbreviated title of the trial where available
    Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC)
    A.4.1Sponsor's protocol code numberINSIGHT-012-OTAC
    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 Minnesota
    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 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+4536 47 33 40
    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.3.1Product nameAnti-COVID-19 Hyperimmune Globulin (Human)
    D.3.2Product code Grifols hIVIG
    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 INNImmune Globuiln Convalescent Plasma (Human)
    D.3.9.3Other descriptive nameHUMAN IMMUNOGLOBULIN G
    D.3.9.4EV Substance CodeSUB127300
    D.3.10 Strength
    D.3.10.1Concentration unit g/ml gram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.1
    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 Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects recently tested positive for SARS-CoV-2 infection
    E.1.1.1Medical condition in easily understood language
    Infection with Coronavirus SARS-CoV-2/COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10084268
    E.1.2Term COVID-19
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Among outpatients with recently diagnosed SARS-CoV-2 infection to compare the safety and efficacy of a single infusion of hyperimmune immunoglobulin (hIVIG) versus placebo, each given with standard of care (SOC), on clinical status after seven days. Two hypotheses will be tested to address this primary objective, which compares the primary endpoint among two study populations: 1) participants where a direct-acting antiviral (DAA) or other anti-SARS-CoV-2 agent was not prescribed as part of SOC treatment (stratum 1, see Section 6.1); and 2) all randomized participants (stratum 1 and stratum 2 combined). Stratum 2 is defined by prescribed treatments in SOC that include: DAA or other anti-SARS-CoV2 agents that are recommended for use by established national or international COVID-19 treatment guidelines. The hIVIG treatment will be considered superior to placebo if either of the two hypotheses are rejected.
    E.2.2Secondary objectives of the trial
    Secondary objectives, including subgroup analysis and safty outcomes, will be assesed for all randomised participants and for those in stratum 1 and stratum 2 separatly.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
    2. Positive test for SARS-CoV-2 within ≤5 days (if >1 test, the first positive is within ≤5 days). Tests may include an institutional-based nucleic acid amplification test (NAAT), or any protocol-approved rapid test.
    3. Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
    4. Agrees to not participate in another clinical trial for the treatment or management of SARS-CoV-2 infection through Day 7, or until hospitalized or significant disease progression if prior to Day 7 (defined by ordinal category 4 or 5).
    5. Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day 28.

    Information on which patient populations may benefit most from passive immune strategies targeting SARS-CoV-2 are limited. However, patients with impaired immune responses, whether from an underlying condition or the result of medical treatments, may have a delayed and/or reduced endogenous antibody response during COVID-19.
    Ongoing immunosuppressive condition or immunosuppressive treatment, includes:
    • Steroids equivalent to prednisone > 10 mg/day for at least the last 28 days
    • Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy
    • Antirejection medicine after solid organ or stem cell transplantation
    • Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months
    • Primary or acquired severe B- or T-lymphocyte immune dysfunction
    • HIV infection
    • Splenectomy or functional asplenia
    E.4Principal exclusion criteria
    1. Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours).
    2. Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
    3. Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
    4. Evidence of pneumonia and/or hypoxia due to COVID-19 (NOTE: chest imaging is not required, but if available it should not show new infiltrates suggestive of pneumonia; hypoxia is defined by new oxygen supplementation or increase above pre-illness level).
    5. Prior receipt of immunoglobulin product or passive immune therapy for SARS-CoV-2 in the past 90 days (i.e., convalescent plasma, SARS-CoV-2 monoclonal antibodies, or any IVIG).
    6. Any of the following thrombotic or procoagulant conditions or disorders:
    • acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization.
    • prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antiphospholipid syndrome, or a deficiency in antithrombin III, protein C, or protein S.
    7. History of hypersensitivity to blood, plasma or IVIG excipients.
    8. Known IgA deficiency or anti-IgA antibodies.
    9. Medical conditions for which receipt of a 300 mL volume of IV fluid from study treatment may pose specific risk to the patient (e.g., decompensated congestive heart failure).
    10. In the opinion of the investigator, any condition for which participation would not be in the best interest of the participant or that could prevent or confound protocol assessments.
    E.5 End points
    E.5.1Primary end point(s)
    The goals of this study are to assess the safety and efficacy of a single infusion of hIVIG in preventing further progression related to COVID-19 when administered early after diagnosis and symptom onset (if symptomatic), with a further aim to concurrently assess for more rapid resolution of illness and restoration of health status to the pre-illness state. There is as yet no consensus on the optimal endpoint for determining clinical benefit from COVID-19 therapies in the ambulatory care setting, including the constituent elements of the endpoint and the timing of its assessment after a given treatment.
    The primary endpoint is the participant’s clinical status through Day 7, as defined by five mutually exclusive categories on an ordinal scale:
    1. Asymptomatic and no limitations in usual activity due to COVID-19
    2. Mild COVID-19 illness or minor limitations to usual activity
    3. Moderate COVID-19 illness and major limitations to usual activity
    4. Severe COVID-19 or other serious disease manifestation
    5. Critical illness from COVID-19 or Death
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 7 was chosen for the timing of the primary endpoint for several reasons based on the following assumptions. The impact of hIVIG on disease progression may not be immediate; a few days may be needed to see the effects on clinical outcomes as measured by the ordinal outcome. Also, antibody differences between groups who receive passive immunotherapy versus those who do not are assumed to be greatest during the first week after infusion. Assessment of the ordinal outcome at a later time point may result in a diminished treatment difference because a greater proportion of participants may be transitioning through spontaneous recovery from COVID-19.
    E.5.2Secondary end point(s)
    The clinical status as classified on the ordinal outcome scale will be assessed with a number of additional analyses comparing hIVIG (pooled for the 2 hIVIG products) with placebo, among the overall study population as well as for the key subgroup of those not receiving anti-SARS-CoV-2 monoclonal antibodies as part of SOC (stratum 1), including:
    1. All-cause hospitalization or death through 28 days.
    2. All-cause mortality through 28 days.
    3. Significant disease progression through 28 days, using a time to event analysis with outcome defined by fulfilling criteria for category 4 or 5 on the ordinal scale.
    4. Distribution of ordinal scale outcome at Day 4, 14, and 28.
    5. The proportion of participants with any disease progression at Day 7, using a sliding dichotomous scale progression defined by a categorization on the ordinal scale that is worse than the status at entry.
    6. The proportion of participants who progress to categories 3-5 on the clinical ordinal scale at Day 7 among participants in categories 1 or 2 of the ordinal scale at entry.
    7. The severity of progression during follow-up, defined by the worst health status achieved on the clinical ordinal scale at any point by Day 7, 14, and 28.
    8. The proportion of participants that attain their pre-COVID health status without limitations in usual activity (i.e., category 1) at Day 7, 14, and 28.
    9. Change in quantitative measures of viral burden between Day 0 and Day 7, including serum antigen levels (e.g., nucleocapsid antigen) as well as by polymerase chain reaction (PCR) from nasal and saliva specimens.
    10. Change in SARS-CoV-2 antibody levels between Day 0 and Day 7, including subclasses and neutralizing titers.
    11. Utilization of health care resources through 28 days, defined by the proportion of participants that had health care engagement for the purposes of medical evaluation and/or management of COVID-19 illness (e.g., via telehealth, clinic, urgent care, emergency room, or hospitalization).
    12. The severity of respiratory symptoms and dysfunction, as the worst status through 28 days, including: a) no respiratory symptoms, b) upper respiratory symptoms, c) lower respiratory symptoms without hypoxia, c) hypoxia requiring conventional oxygen supplementation by nasal canula, d) respiratory failure requiring high-flow oxygen delivery device or non-invasive ventilation, or e) respiratory failure requiring mechanical ventilation or extra-corporeal membrane oxygenation (ECMO).
    13. Hypoxemia through Day 7, as evaluated through participant assessments of saturation of oxygen (SpO2) levels. Comparisons between groups will consider differences in SpO2 levels as well as explore the frequency of levels that drop below clinical thresholds (e.g., <94% and <90% on room air for those without COPD or use of supplemental O2 prior to COVID-19).
    14. Proportion of patients starting other treatments targeting COVID-19.
    15. Associations between changes in laboratory assessments from Day 0 to Day 7, and ordinal scale distribution and clinical outcomes over follow-up.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 0-7 and the 28 day follow-up period.
    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) No
    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 No
    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 trial2
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Argentina
    Nigeria
    Peru
    Israel
    Japan
    Mexico
    Thailand
    United Kingdom
    United States
    Denmark
    France
    Germany
    Greece
    Spain
    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: 600
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 No
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 820
    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 Decision2021-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-10-13
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 04 00:23:35 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA