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    Summary
    EudraCT Number:2018-002010-12
    Sponsor's Protocol Code Number:FIRE-6
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-01-02
    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 - PEI
    A.2EudraCT number2018-002010-12
    A.3Full title of the trial
    Avelumab added to FOLFIRI plus Cetuximab followed by Avelumab maintenance in patients with previously untreated RAS/BRAF wild-type metastatic colorectal cancer - The phase II FIRE-6-Avelumab study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Avelumab added to FOLFIRI plus Cetuximab followed by Avelumab maintenance in patients with previously untreated RAS wild-type colorectal cancer - The phase II FIRE-6-Avelumab study
    A.3.2Name or abbreviated title of the trial where available
    AIO KRK-0118/FIRE-6
    A.4.1Sponsor's protocol code numberFIRE-6
    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 SponsorKlinikum der Ludwig-Maximilians-Universität München - Klinikum Großhadern (vertreten durch den kaufmännischen Direktor)
    B.1.3.4CountryGermany
    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 supportMerck GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKlinikum der Ludwig-Maximilians-Universität München - Klinikum Großhadern - Studiensekratariat
    B.5.2Functional name of contact pointMatthias Wolff
    B.5.3 Address:
    B.5.3.1Street AddressMarchioninistr. 15
    B.5.3.2Town/ cityMünchen
    B.5.3.3Post code81377
    B.5.3.4CountryGermany
    B.5.4Telephone number004989440072208
    B.5.5Fax number004989440075256
    B.5.6E-mailMatthias.Wolff@med.uni-muenchen.de
    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 Bavencio
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Serono Europe Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical 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 INNAVELUMAB
    D.3.9.1CAS number 1537032-82-8
    D.3.9.2Current sponsor codeAvelumab
    D.3.9.4EV Substance CodeSUB180078
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    D.3.11.13.1Other medicinal product typefull human IgG1 antibody directed against PD-L1
    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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameIrinotecan
    D.3.4Pharmaceutical form Concentrate for 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 INNIRINOTECAN
    D.3.9.1CAS number 97682-44-5
    D.3.9.4EV Substance CodeSUB08295MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.IMP: 3
    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 Erbitux
    D.2.1.1.2Name of the Marketing Authorisation holderMerck KGaA
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical 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 INNCETUXIMAB
    D.3.9.1CAS number 205923-56-4
    D.3.9.4EV Substance CodeSUB01178MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 Yes
    D.3.11.13.1Other medicinal product typemonoclonal IgG1 antibody
    D.IMP: 4
    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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 name5-Fluorouracil
    D.3.2Product code L01BC02
    D.3.4Pharmaceutical form Solution for injection
    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 INNFLUOROURACIL
    D.3.9.3Other descriptive nameFLUOROURACIL
    D.3.9.4EV Substance CodeSUB07721MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.IMP: 5
    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.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameFolinic acid
    D.3.4Pharmaceutical form Concentrate for solution for injection/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 INNFOLINIC ACID
    D.3.9.3Other descriptive nameFOLINIC ACID
    D.3.9.4EV Substance CodeSUB13910MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Avelumab added to FOLFIRI plus cetuximab followed by avelumab maintenance in patients with previously untreated RAS/BRAF wild-type metastatic colorectal cancer - the phase II FIRE-6-avelumab study
    E.1.1.1Medical condition in easily understood language
    metastatic colorectal cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 100000004864
    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 the study is to assess the efficacy of FOLFIRI plus cetuximab in
    combination with avelumab followed by avelumab maintenance therapy in patients with
    previously untreated RAS/BRAF wild-type mCRC.
    E.2.2Secondary objectives of the trial
    • To assess the efficacy and safety profile of the tested treatment strategy
    • To assess the feasibility of the tested treatment strategy
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically confirmed, UICC stage IV adenocarcinoma of the colon or rectum with metastases (mCRC), metastases primarily non resectable
    or surgery refused by the patient
    2. RAS wild-type tumour status (KRAS and NRAS, exon 2, 3, 4) and BRAF wild-type tumour status (V600, exon 15) (proven in the primary
    tumour or metastasis)
    3. Adult patients ≥ 18 years
    4. ECOG performance status 0-1
    5. Patients suitable for chemotherapy administration
    6. Patient's written declaration of consent obtained
    7. Estimated life expectancy > 3 months
    8. Presence of at least one measurable reference lesion according to the RECIST v1.1 criteria
    9. Tumour tissue available for molecular and genetic profiling regarding BRAF/RAS mutation status and MSI Status
    10. Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index <1) or practice true abstinence from any heterosexual intercourse (true abstinence is acceptable if this is in line with the patient’s preferred and usual lifestyle) for the duration of study treatment and at least 6 months after the last study treatment. A woman will be considered as being of childbearing potential unless she is at least 50 years old and has gone through menopause for at least 2 years or has been surgically sterilised.
    11. Males must agree to use condoms or practice true abstinence from any heterosexual intercourse (true abstinence is acceptable if this is in line
    with the patient’s preferred and usual lifestyle) for the duration of study treatment and at least 6 months after the last study treatment. Male
    patients must refrain from donating sperm during the study until 6 months after the administration of the last study medication.
    12. Adequate bone marrow function:
    a) Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L
    b) Thrombocytes ≥ 100 x 109/L
    c) Haemoglobin ≥ 5.6 mmol/L (equivalent to 9 g/dL)
    13. Adequate hepatic function:
    a) Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
    b) ALT and AST ≤ 2.5 x ULN (in the presence of hepatic metastases, ALT and AST ≤ 5 x ULN)
    c) INR < 1.5 and aPTT < 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is allowed if INR and aPTT have remained stable within the therapeutic range for at least 2 weeks.
    14. Adequate renal function: Creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50 mL/min
    15. Adequate cardiac function: ECG and echocardiogram with a LVEF of ≥ 55%
    16. No previous chemotherapy for metastatic disease. Patient with need of immediate treatment (high tumour load, symptoms) may have received
    one application of FOLFIRI prior to study entry.
    17. Time interval since last administration of any previous neoadjuvant/adjuvant chemotherapy or radiochemotherapy of the primary tumour in curative treatment intention ≥ 6 months.
    18. Any relevant toxicities of prior treatments must have resolved
    19. Patient covered by health insurance
    E.4Principal exclusion criteria
    1. Proof of a RAS mutation (KRAS or NRAS, exons 2, 3, 4) or BRAF mutation (V600 in exon 15) in the tumour (proven in primary tumour
    or metastasis) or absence of testing for RAS or BRAF mutations
    2. Primarily resect metastases and the patient wishes for resection
    3. ≥ Grade II heart failure (NYHA classif)
    4. Myocardial infarct, balloon angioplasty (PTCA) with or without stenting + cerebral vascular accident/stroke within the past 12 months before start of study treatm, unstable angina pectoris, serious cardiac arrhythmia according to investigator’s judgem. requiring medic.
    5. Pre-existing pulmonary fibrosis or immune pneumonitis
    6. Active autoimmune disease that might be negatively affected by an immune checkpoint inhibitor. Patients diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosup. treatment are eligible.
    7. Prior organ transpl., incl allogeneic stem cell transpl.
    8. Current use of immunosuppressive medi, except for the following:
    a) Intranasal, inhaled, topical steroids, or local steroid inject (e.g., intra-articular inject);
    b) System corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
    c) Steroids as premedic. for hypersens reactions (e.g., CT scan premedi).
    9. Pregnancy (absence of pregnancy to be ascertained by a negative β-HCG test) or breast feeding
    10. Medi or psychol impairments assoc. with restricted ability to give consent or not allowing conduct of the study
    11. Add cancer treatm (chemoth., radiation, immunoth or hormone treatm.) during the study treatm in first-line
    (treatm that are conducted as part of an anthroposophic or homeopathic treatm approach, e.g. mistletoe therapy do not represent an excl.cr.)
    12. Previous chemoth. for the Color. cancer with the exception of adjuvant treatm., compl at least 6 months bef. entering the study
    13. Adv. drug reaction > NCI CTCAE Grade1 that has not yet resolved, attributed to a previous treatm or measure for treatm of the CRC. However, alopecia (all grades) and oxaliplatin-induced neurotox ≤ grade 2 are acceptable.
    14. Participat in a clinic study or experim. drug treatm within 30 days prior to study incl. or within a period of 5 half-lives of the
    substances admin. in a clinical study or during an experimental drug treatm prior to incl. in the study, depending on which
    period is longest or simultaneous participation in another study while taking part in the study
    15. Known hypersensitivity or allergic react to any of the following substances: folinic acid, 5-FU, irinotecan, cetuximab,
    avelumab and chemically related substances and/or hypersens to any of the components in the formulations of the aforementioned
    subst, incl known hypersensitivity reactions to monoclonal antibodies NCI CTCAE Grade ≥ 3.
    16. Known hypersensitivity to Chinese hamster ovary cell (CHO) – cellular products or other recombinant human or humanised monocl antibodies
    17. Patients with known brain metastases. In case of clinical suspicion of brain metastasis a cranial MRI or CT must be performed to rule out brain metastasis bef. study inclus.
    18. History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhoea
    19. Symptomatic peritoneal carcinosis
    20. Severe, non-healing wounds, ulcers or bone fractures
    21. Patients with act. infect requiring syst. therapy
    22. Known history of testing positive for HIV or known acquired immunodeficiency syndr.
    23. Active or chronic Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive; serologic tests required).
    24. Requirement for immunisation with live vaccine under the study treatm.
    25. Haemorrhagic diathesis or known thrombophilia
    26.Known complete DPD deficiency (spec. screen accor to the recommend of the SmPC in effect for 5-FU; pat. with a known compl DPD deficiency must be excluded; (further see Protocol)
    27. Known glucuronidation deficiency (Gilbert's syndrome) (spec screen not required)
    28. Treatm with sorivudine or brivudine within 28 days before study enrollm or requirement for concom antiviral treatm with
    sorivudine or brivudin
    29. History of a second primary malignancy dur. the past 5 years before incl. in the study or during participat in the study, with the
    except of a basal cell or squamous cell carcinom of the skin or cervical carcinom in situ, if these were treated curatively.
    30. Known history of alcohol or drug abuse
    31. Any other severe acute or chronic concom. disease or medical condition incl psychiatric conditions (incl recent i.e. within the past year or active suicidal ideation or behaviour) or labor. abnorm that may incr. the risk associated with study participation or study treatm. administr or may interfere with the interpret of study results and, in the judgm of the invest, would make the pat inappropriate for entry into this study.
    32. Absent or restricted legal capacity
    E.5 End points
    E.5.1Primary end point(s)
    • Progression-free survival (PFS) according to RECIST v1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Restaging according to RECIST 1.1 will be performed every eight weeks
    E.5.2Secondary end point(s)
    • Objective response rate (ORR) according to RECIST v1.1 and irRECIST
    • Progression-free survival (PFS) according to irRECIST
    • Progression-free survival rate after 12 months of treatment (PFSR@12) according to RECIST v1.1 and irRECIST
    • Overall survival (OS)
    • Duration of treatment
    • Type, frequency and severity of adverse events (severity according to NCI CTCAE version 5.0)
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Restaging according to RECIST 1.1 will be performed every eight weeks
    • OS will be evaluated in a continously manner, after study Treatment every 3 month until death or end of study
    • Evaluated when end of treatment is reached
    • Safety and tolerability will be evaluated in a continously manner
    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 Yes
    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 No
    E.8.1.1Randomised No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned15
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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.1.3Elderly (>=65 years) Yes
    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 No
    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 state55
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-04-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-30
    P. End of Trial
    P.End of Trial StatusOngoing
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