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   43874   clinical trials with a EudraCT protocol, of which   7294   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:2020-004206-59
    Sponsor's Protocol Code Number:ATR-002-202
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-09-23
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-004206-59
    A.3Full title of the trial
    RESPIRE - A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial, conducted at multiple trial sites, to test the safety and effectiveness of ATR-002 in hospitalized patients diagnosed with the lung disease COVID-19.
    A.3.2Name or abbreviated title of the trial where available
    Safety and Efficacy of ATR-002 for Hospitalized Patients with COVID-19
    A.4.1Sponsor's protocol code numberATR-002-202
    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 SponsorAtriva Therapeutics GmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAtriva Therapeutics GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAtriva Therapeutics GmbH
    B.5.2Functional name of contact pointClinical Development Solutions
    B.5.3 Address:
    B.5.3.1Street AddressEisenbahnstr. 1
    B.5.3.2Town/ cityTuebingen
    B.5.3.3Post code72072
    B.5.3.4CountryGermany
    B.5.4Telephone number+4970718597673
    B.5.6E-mailTeam.CDS@atriva-therapeutics.com
    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 nameATR-002
    D.3.2Product code ATR-002
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNATR-002
    D.3.9.1CAS number 303175-44-2
    D.3.9.2Current sponsor codeATR-002
    D.3.9.4EV Substance CodeSUB218292
    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 Yes
    D.3.11.13.1Other medicinal product typeATR-002 is an ATP non-competitive MEK1/2 inhibitor.
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Adult hospitalized patients suffering from COVID-19.
    E.1.1.1Medical condition in easily understood language
    Patients suffering from the disease 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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To demonstrate the efficacy of ATR-002 versus placebo in addition to standard of care based on the clinical severity status in adult hospitalized patients with COVID-19
    E.2.2Secondary objectives of the trial
    • To show that ATR-002 in addition to standard of care shortens the time to clinically relevant improvement of COVID-19 for a hierarchically ordered sequence of time-to-event endpoints
    • To show that the primary endpoint extended as AUC has a more favorable level under ATR-002 compared to placebo in addition to standard of care over the initial trial period of 30 days in adult hospitalized patients with COVID-19
    • To explore whether survival time will be prolonged under ATR-002 compared to placebo in addition to standard of care during the initial 30 days of the trial period in adult hospitalized patients with COVID-19
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    2. Study participant must be at least 18 years of age at the time of signing the ICF.
    3. Study participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection presenting as moderate -to-severe COVID-19 requiring hospitalization for COVID-19 (Clinical Severity Status [3] or [4]) and for medical reasons (see Section 8 of the protocol). Patients presenting to the hospital without a laboratory confirmed SARS-CoV-2 infection will be tested locally for SARS-CoV-2 during the screening period.
    For sites in the EU: A CE certified SARS-CoV-2 PCR test kit is required to confirm infection.
    For sites outside the EU: SARS-CoV-2 PCR test kits certified according to local regulations are required to confirm infection.
    4. Body weight at least 50 kg and have a body mass index (BMI) ≥ 18.0 kg/m2 and < 40.0 kg/m2.
    5. Male or female.
    6. A female study participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
    a. She is not a WOCBP as defined in Section 10.3.1 of the protocol.
    b. Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 of the protocol during the IMP period and for at least 4 weeks after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP.
    7. A WOCBP must have a negative urine pregnancy test within 24 hours before the first dose of IMP, see Section 8.3.5 of the protocol.
    a. If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive.
    b. If a serum pregnancy test is required as per local regulations, a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive.
    c. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetectable pregnancy.
    8. A male study participant is eligible to participate if:
    a. He is azoospermic
    b. The partner is not a WOCBP as defined in Section 1.1.1 of the protocol.
    c. The partner is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.3.2 of the protocol during the IMP period and for at least 90 days after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP.
    d. He acknowledges that sperm donation is prohibited from the first dose of IMP until at least 90 days after the last dose of IMP.
    E.4Principal exclusion criteria
    1. Patient’s clinical condition is worsening rapidly.
    2. Requiring ICU admission or ventilator support at screening or at randomization.
    3. Suspected bacterial, fungal, viral, or other infection (besides COVID-19).
    4. History of any of the following: malignant disease, autoimmune disease, or severe liver, kidney, blood, cardiac, pulmonary, neurological, or endocrine disease as judged by the investigator. The medical monitor should be contacted by the investigator.
    5. History of hypertension should have hypertension adequately controlled (BP < 140/90 mmHg) with appropriate anti-hypertensive treatment.
    6. Clinically significant cardiac conduction abnormalities, including QTc prolongation of > 450 milliseconds.
    7. Family history of Long QT Syndrome.
    8. Heart failure class 3, or 4, as defined by the New York Heart Association (NYHA).
    9. History of acute coronary syndrome (including myocardial infarction), coronary angioplasty, or stenting within 24 weeks prior to screening.
    10. Patients with implanted defibrillators or permanent pacemakers.
    11. Poorly controlled diabetes mellitus with an HbA1c > 7.5 %.
    12. Renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.
    13. Renal failure requiring renal replacement therapy or moderate renal impairment as defined by having an estimated glomerular filtration rate (eGFR, CKD-EPI) < 45 ml/min/1.73m2.
    14. Chronic Obstructive Pulmonary Disease (COPD) GOLD C, or D, or hospitalization for exacerbation of COPD within 24 weeks prior to screening.
    15. Other chronic lung diseases including cystic fibrosis, neuromuscular diseases, severe chest wall deformities, interstitial lung diseases, outpatient chronic non-invasive ventilation due to chronic respiratory failure.
    16. Asthma with a symptom control level of "uncontrolled", according to current GINA guidelines.
    17. Currently suffering from diseases that seriously affect the immune system, such as: human immunodeficiency virus (HIV) infection, or the blood system, or splenectomy, or organ/ stem cell transplantation.
    18. Known Hepatitis B or C infection.
    19. Any medical condition, physical examination finding or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient.
    20. Alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 x ULN.
    21. Total bilirubin >1.0 x ULN (≥1.5 x ULN total bilirubin if known Gilbert’s syndrome).
    22. Taking concomitant medication metabolized by CYP2C8 and/ or CYP2C9 and listed as “prohibited” in Section 10.5 of the protocol.
    23. Taking concomitant medication of any experimental treatment or use of marketed medications including off-label use, that are intended as specific treatment for COVID-19. Any such treatments must be washed out for 30 days or at least 5 half-lives prior to randomization, whichever is longer, unless a formal written standard of care policy document requires otherwise. Inclusion needs to be approved by the investigator and medical monitor.
    24. Taking medication that may seriously affect the immune system, e.g. chemotherapy, unless considered and documented as standard of care (e.g. corticosteroids) to treat COVID-19.
    25. Currently participating in other clinical trials or previous treatment with an investigational medicinal product within 5 half-lives or 30 days (whichever is longer) prior to randomization.
    26. Known allergy or hypersensitivity to the IMP (including excipients).
    27. Study participant is pregnant or breastfeeding.
    28. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
    29. Patient is an employee of the sponsor, or an employee of any third-party organization involved into the clinical trial, or an employee of the clinical trial site, or is dependent on the investigator.
    E.5 End points
    E.5.1Primary end point(s)
    • Population: All study participants fulfilling the inclusion and exclusion criteria
    • Target variable: Clinical severity status on a 7-point ordinal scale at Day 15
    • Estimator: Odds ratio of ATR-002 in addition to standard of care versus placebo in addition to standard of care with 95% confidence interval
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Fulfillment of In-/exclusion criteria on day 1
    • Target variable on day 15
    E.5.2Secondary end point(s)
    • Population defined as above
    • Target variables:
    - Time from randomization to discharge from hospital
    - Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2, whichever occurs first
    - Time to resolution of fever, defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic) for at least 24 hours without antipyretics for 24 hours
    - Time to SpO2 >94% on room air maintained for 24 hours
    - Clinical severity status over the hospital period calculated as AUC from the 7-point ordinal scale at Days 3, 5, 8, 11, 15 and 30
    - Survival time up to Day 30
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Population on day 1
    • Target variables:
    - At any timepoint up to day 30
    - Clinical severity status on days 3, 5, 8, 11, 15 and 30
    - Survival time up to day 30
    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 Yes
    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 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 concerned12
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Brazil
    India
    Mexico
    South Africa
    Turkey
    Germany
    Netherlands
    Poland
    Romania
    Spain
    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 years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    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: 120
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 160
    F.4.2.2In the whole clinical trial 220
    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)
    There are no specific post trial treatment plans. After participation in the trial has ended, the subjects will receive standard of care (SOC) treatment as necessary.
    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 Decision2020-12-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-08-09
    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-Fri May 17 00:01:19 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA