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    Summary
    EudraCT Number:2012-003650-88
    Sponsor's Protocol Code Number:BAY94-9343/15743
    National Competent Authority:Finland - Fimea
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-10-06
    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 ConcernedFinland - Fimea
    A.2EudraCT number2012-003650-88
    A.3Full title of the trial
    A randomized, open-label, active-controlled, Phase II study of intravenous anetumab ravtansine (BAY 94-9343) or vinorelbine in patients with advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin and progressed on first line platinum/pemetrexed-based chemotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study investigating the efficacy and safety of anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma.
    A.3.2Name or abbreviated title of the trial where available
    Phase II anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma (MPM) ARCS-M2L
    A.4.1Sponsor's protocol code numberBAY94-9343/15743
    A.5.4Other Identifiers
    Name:Mesothelin-ADCNumber:BAY94-9343
    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 SponsorBayer AG
    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 supportBayer AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.6E-mailclinical-trials-contact@bayer.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 Yes
    D.2.5.1Orphan drug designation numberEMA/OD/063/12
    D.3 Description of the IMP
    D.3.1Product nameAnetumab Ravtansine
    D.3.2Product code BAY 94-9343
    D.3.4Pharmaceutical form Lyophilisate for 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 INNAnetumab Ravtansine
    D.3.9.3Other descriptive nameBAY 94-9343
    D.3.9.4EV Substance CodeSUB178041
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 NAVELBINE 10mg
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Pharma
    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 namevinorelbine
    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 INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 NAVELBINE 50mg
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Pharma
    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 namevinorelbine
    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 INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    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
    Patients with advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic malignant pleural mesothelioma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10035605
    E.1.2Term Pleural mesothelioma malignant advanced
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Test the superiority of anetumab ravtansine monotherapy over vinorelbine in progression-free survival (PFS)
    E.2.2Secondary objectives of the trial
    • Test overall survival
    • Evaluate patient-reported outcomes – symptom burden and health-related quality of life (QoL)
    • Evaluate other indicators of treatment efficacy
    • Evaluate safety

    The other objectives of this study are to evaluate the:
    • Pharmacokinetics and immunogenicity
    • Biomarkers
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Eligibility criteria for mesothelin expression testing:
    1. Written informed consent for mesothelin expression testing.
    2. Unresectable locally advanced or metastatic MPM, confirmed by histology.
    3. Availability of archival or fresh tissue for testing of mesothelin expression level.
    Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival tissue is available and if in the investigator’s judgement, there is no additional risk for the patient’s safety.
    4. Age ≥ 18 years (age limit may be higher if legally required in a country e.g. in Japan adult age is considered ≥ 20 years).
    5. ECOG PS of 0 or 1 (specified in Section 16.1).
    6. Life expectancy of at least 3 months.
    7. No prior treatment with anetumab ravtansine or vinorelbine.
    8. No prior use of targeted agents, experimental therapy or systemic anti-cancer treatment other than ongoing or completed 1st line platinum/pemetrexed (with or without bevacizumab).

    Eligibility criteria for study treatment
    1. Written informed consent for full study.
    2. Histological documentation of MPM overexpressing mesothelin at the moderate and stronger level in at least 30% of tumor cells as determined by centrally performed IHC
    Note: Patients with a sarcomatoid histology are not expected to have mesothelin overexpression and should not be enrolled in the study.
    3. Unresectable locally advanced or metastatic MPM after progression on 1st line treatment with platinum in combination with pemetrexed. Last dose of previous therapy must be at least 28 days before start of study treatment.
    Note: Patients progressed on 1st line treatment with platinum plus pemetrexed in combination bevacizumab are allowed
    4. Patients must have at least 1 measurable lesion according to mRECIST for mesothelioma i.e. pleural lesion(s) measured using mRECIST or extra-pleural lesion(s) measurable per RECIST 1.1. This will be confirmed by central review of images before the patient can be randomized into the study.
    Note: In case the only site of disease was previously treated with radiotherapy, there should be evidence of unequivocal PD in this site: measurable pleural disease should be assessed on a contrast enhanced CT/MRI done at the minimum 4 weeks after the end of radiotherapy and compared with previous imaging; unequivocal progression should be judged by the investigator as per mRECIST per MPM
    5. Age ≥ 18 years (age limit may be higher if legally required in a country e.g. in Japan adult age is considered > 20 years)
    6. ECOG PS of 0 or 1
    7. Life expectancy of at least 3 months
    8. Women of childbearing potential (WOCBP) and men must agree to use adequate contraception from signing of the ICF for full study until at least 4 months after the last study drug administration. Men being treated with vinorelbine are advised not to father a child during and up to 6 months after treatment; for all male patients, prior to treatment with either study drug, advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment (22).The investigator or a designated associate is requested to advise the patient how to achieve an adequate birth control. Highly effective (failure rate of less than 1% per year) contraception methods (23) include: (...)
    9. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment:
    • Total bilirubin < 1.5 x the upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is mildly elevated (< 6 mg/dL).
    • ALT and AST < 3 x ULN (< 5 x ULN for patients with liver involvement of their cancer).
    • ALP limit < 2.5 x ULN (< 5 x ULN for patients with liver involvement of their cancer).
    • Amylase and lipase < 1.5 x ULN.
    • Serum creatinine < 1.5 x ULN
    • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula
    • Adequate coagulation, as assessed by the following laboratory test results:
    o International normalized ratio (INR) or prothrombin time (PT) < 1.5 x ULN (CTCAE Grade < 1)
    o Partial thromboplastin time (PTT) or activated PTT (aPTT) < 1.5 x ULN (CTCAE Grade < 1)
    Note: Patients on anti-coagulation therapy will be allowed to participate if INR / PT and PTT / aPTT test results are compatible with the acceptable benefit-risk ratio at the investigator’s discretion
    • Platelet (PLT) count > 100000/mm3 , without PLT transfusion within 3 weeks before the start of study treatment
    • Hemoglobin (Hb) > 9 g/dL, without blood transfusion or erythropoietin within 6 weeks before the start of study treatment
    • Absolute neutrophil count (ANC) > 1500/mm3, without biologic response modifiers, such as G-CSF, within 6 weeks before the start of study treatment
    10. Left ventricular ejection fraction (LVEF) ≥ 50% of the lower limit of normal (LLN) according to local institution ranges of normality.
    E.4Principal exclusion criteria
    1. Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
    2. Previous (within 5 drug half-lifes – if drug half-life in subjects is known – or 28 days, whichever is shorther, before the start of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s).
    3. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
    4. More than 1 previous systemic anti-cancer therapy line for MPM (even if therapy used as neoadjuvant or adjuvant treatment).
    Note: Patients pre-treated with systemic therapy other than platinum, pemetrexed, bevacizumab (e.g. other cytotoxic drugs, immunotherapy, targeted therapy, hormonal therapy, or any other experimental or approved therapy or device) are not to be enrolled.
    5. Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator in consultation with the ophthalmologist/optometrist.
    Note: Low grades of superficial punctate keratitis, within the range seen in the normal population, should not lead to the exclusion of the patient.
    6. Previous or concurrent cancer that is distinct in primary site or histology from mesothelioma within 5 years before randomization.
    Exceptions: curatively treated
    • Cervical cancer in situ.
    • Non-melanoma skin cancer.
    • Superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
    7. Major surgery, open biopsy or significant traumatic injury within 28 days before the start of study treatment.
    8. Pregnant or breast-feeding patients. WOCBP must have a serum pregnancy test performed a maximum of 7 days before the start of study treatment, and a negative result must be documented before the start of study treatment.
    9. Pre-existing cardiac conditions as outlined below:
    • Congestive heart failure > New York Heart Association (NYHA) class 2
    • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before the start of study treatment.
    • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
    10. Clinically significant uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
    11. Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or venous pulmonary embolism within 6 months before the start of study treatment; venous thrombotic events as deep vein thrombosis within 3 months before the start of study treatment.
    12. Ongoing or active infection (bacterial, fungal, or viral) of NCI-CTCAE version 4.03 Grade > 2.
    13. Known history of human immunodeficiency virus (HIV) infection.
    14. Known history of chronic hepatitis B or C.
    15. Patients with seizure disorder requiring medication.
    16. Brain metastases or meningeal tumors or other metastases in the central nervous system (CNS). Patients with neurological symptoms must undergo a contrast CT scan or MRI of the brain and/or other areas of the CNS as applicable within 28 days before the start of study treatment to exclude metastastic disease in the CNS.
    17. History of organ allograft, stem cells or bone marrow transplant.
    18. Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event > CTCAE Grade 3 within 4 weeks before the start of study treatment.
    19. Non-healing wound, ulcer, or bone fracture.
    20. Renal failure requiring peritoneal or hemodialysis.
    21. Known hypersensitivity to anetumab ravtansine or vinorelbine, study drug classes or excipients in the formulation.
    22. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
    23. Unresolved toxicity higher than NCI-CTCAE version 4.03 Grade 1 attributed to any prior therapy/procedure excluding anemia Grade 2 and alopecia of any Grade.
    24. Any prohibited prior or concomitant therapy
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint is progression free survival.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assuming true median PFS of 3.6 months under vinorelbine treatment and constant hazards, the study primary hypothesis test is designed to detect a 100% prolongation of true PFS (median 7.2 months) in the anetumab ravtansine arm in comparison to the comparator arm (hazard ratio 0.5) with 90% power with a 1-sided significance level of 0.0125.
    The final primary endpoint analysis will be performed after approximately 117 PFS events have been observed.
    The 210 randomized patients are estimated to be accrued in approximately 19.8 months. Data for final PFS analysis are estimated to mature in 21.2 months.
    E.5.2Secondary end point(s)
    The secondary endpoint is overall survival.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Assuming true median OS of 9.6 months under vinorelbine treatment and constant hazards, a 60% prolongation of true OS (median 15.4 months) in the anetumab ravtansine arm in comparison to the comparator arm (median 9.6 months) can be detected with an overall 80% power and an overall 1-sided significance level of 0.025 (hazard ratio 0.625), with a 2-stage group sequential test with a total of 159 events. An interim OS analysis will be performed at the time of the final PFS analysis at an estimated 22 months from first patient randomized, when an estimated 80 OS events will have been observed. If the study is not stopped for superiority at the OS IA, the final OS analysis will occur after approximately159 OS events have been observed, at approximately 41.3 months from first patient randomized
    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 Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group 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) Yes
    E.8.2.2Placebo No
    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 Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    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
    Australia
    Belgium
    Canada
    Finland
    France
    Germany
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Poland
    Russian Federation
    Spain
    Turkey
    United Kingdom
    United States
    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
    For each participating EU country, the end of the study according to the EU Clinical Trial
    Directive will be reached when the last visit of the last patient for all centers in the respective
    country has occurred.
    As for this study, important data will be collected after LPLV, the end of the study as a whole
    will be the date when the clean database is available.
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 115
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 95
    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 state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 210
    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 Decision2015-11-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-08-09
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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