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    Summary
    EudraCT Number:2017-003190-34
    Sponsor's Protocol Code Number:ACE-536-MDS-002
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-09-26
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2017-003190-34
    A.3Full title of the trial
    A Phase 3, Open -label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) versus Epoetin alfa for the Treatment of Anemia due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects who require Red Blood Cell Transfusions.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 study to see the benefit and safety of Luspatercept in comparison with Epoetin Alfa to treat anaemia due to very low, low or intermediate risk Myelodysplastic Syndromes (MDS) in people who have not taken erythropoiesis-stimulating agents (ESA's) before and who require red blood cell transfusions.
    A.3.2Name or abbreviated title of the trial where available
    The Commands Trial
    A.4.1Sponsor's protocol code numberACE-536-MDS-002
    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 SponsorCelgene Corporation
    B.1.3.4CountryUnited States
    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 supportCelgene Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD
    B.5.2Functional name of contact pointPPD Project Manager
    B.5.3 Address:
    B.5.3.1Street Addressvia San Bovio, 3
    B.5.3.2Town/ citySan Felice Segrate, Milan
    B.5.3.3Post code20090
    B.5.3.4CountryItaly
    B.5.4Telephone number+390282951230
    B.5.5Fax number+39023271659
    B.5.6E-mailSimone.Pizzimenti@ppdi.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 numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.3Other descriptive nameLuspatercept
    D.3.9.4EV Substance CodeSUB189400
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number37.5
    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 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 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 numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.3Other descriptive nameLuspatercept
    D.3.9.4EV Substance CodeSUB189400
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number87.5
    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 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: 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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000 (0.5 ml)
    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 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: 4
    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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10000 (0.4 ml)
    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 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: 5
    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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10000 (0.6 ml)
    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 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: 6
    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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (0.5 ml)
    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 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: 7
    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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (0.75 ml)
    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 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: 8
    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 Eprex
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (1 ml)
    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 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: 9
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000 (0.5 ml)
    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 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: 10
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10000 (0.4 ml)
    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 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: 11
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10000 (0.6 ml)
    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 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: 12
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (0.5 ml)
    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 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: 13
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (0.75 ml)
    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 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: 14
    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 ERYPO® FS
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag GmbH
    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 injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoetin Alfa
    D.3.9.1CAS number 113427-24-0
    D.3.9.4EV Substance CodeSUB06575MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/ml international unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000 (1 ml)
    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 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.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
    Myelodysplastic syndrome (MDS)
    E.1.1.1Medical condition in easily understood language
    Umbrella term for disorders of the bone marrow, leading to a reduced number of red blood cells.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10068361
    E.1.2Term MDS
    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
    To evaluate the efficacy of luspatercept on red blood cell transfusion independence (RBC-TI; for 12 weeks [84 days] with an associated concurrent mean hemoglobin increase ≥ 1.5 g/dL) compared with epoetin alfa for the treatment of anemia due to very low, low, or intermediate risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System -Revised IPSS-R) in erythropoiesis stimulating agent (ESA) naïve subjects who require RBC transfusions.
    E.2.2Secondary objectives of the trial
    • To assess the safety and efficacy of luspatercept compared to epoetin alfa
    • To assess health-related quality of life (HRQoL) and anemia outcome measures (ie, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire [EORTC QLQ-C30] and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire for subjects treated with luspatercept compared to epoetin alfa
    • To evaluate population pharmacokinetics and exposure-response relationships for luspatercept in MDS subjects
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
    2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
    3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
    4. Subject has a documented diagnosis of MDS according to WHO 2016 classification that meets IPSS R classification of very low, low, or intermediate risk disease, and < 5% blasts in bone marrow.
    5. Subject has an endogenous serum erythropoietin (sEPO) level of < 500 U/L.
    6. Subject requires RBC transfusions, as documented by the following criteria:
    • A transfusion requirement of 2 to 6 pRBCs units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization.
    Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 9.0 g/dL (5.6 mmol/L) with symptoms of anemia (or ≤ 7 g/dL [4.3 mmol/L] in the absence of symptoms) in order for the transfusion to be counted towards meeting eligibility criteria. Red blood cell transfusions administered when Hgb levels were > 9.0 g/dL (or > 7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification.
    The hemoglobin level after the last RBC transfusion prior to randomization must be < 11.0 g/dL (6.8 mmol/L) (centrally or locally analyzed).
    7. Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
    8. Females of childbearing potential (FCBP), defined as a sexually mature woman who:
    1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must:
    •Have two negative pregnancy tests as verified by the investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of W1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
    •If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
    9. Male subjects must:
    •Practice true abstinence (which must be reviewed prior to each IP administration or on a monthly basis [eg, in the event of dose delays]) or agree to use a condom (latex or non-latex, but not made out of natural [animal] membrane) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
    E.4Principal exclusion criteria
    1. Subject with the any of the following prior treatments:
    •Erythropoiesis-stimulating agents (ESAs)
    Subjects may be randomized at the investigator's discretion contingent
    on the fact that the subject received no more than 2 doses of epoetin
    alfa (prior treatment with darbepoetin not acceptable for entry into the
    study). The last dose of epoetin alfa must be ≥ 8 weeks from the date of
    randomization. A blood sample to determine the endogenous sEPO level
    (central laboratory) for stratification must be taken within 5 days of
    randomization unless a prior screening sample analyzed by the central
    laboratory demonstrated an endogenous sEPO level ≤ 500 U/L
    •Granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage
    colony-stimulating factor (GM-CSF), within 8 weeks prior to
    randomization, unless given for treatment of febrile neutropenia
    •Disease modifying agents (eg, immune-modulatory drug [IMiDs such as
    lenalidomide]
    Except if the subject received ≤ 1 week of treatment with a disease
    modifying agent ≥ 8 weeks from randomization, at the investigator's
    discretion.
    •Hypomethylating agents
    Subjects may be randomized at the investigator's discretion contingent
    that the subject received no more than 2 doses of HMA. The last dose
    must be ≥ 8 weeks from the date of randomization.
    •Luspatercept (ACE-536) or sotatercept (ACE-011)
    •Immunosuppressive therapy for MDS
    •Hematopoietic cell transplant
    2. Subject with MDS associated with del(5q) cytogenetic abnormality or
    MDS unclassifiable (MDS-U) according to WHO 2016 classification.
    3. Subject with myelodysplastic/myeloproliferative neoplasms
    (MDS/MPN) according to WHO 2016 classification (ie, Chronic
    myelomonocytic leukemia (CMML), Atypical chronic myeloid leukemia
    (aCML), BCR-ABL12, Juvenile myelomonocytic leukemia (JMML),
    MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T),
    MDS/MPN unclassifiable.
    4. Subject with secondary MDS, ie, MDS that is known to have arisen as
    the result of chemical injury or treatment with chemotherapy and/or
    radiation for other diseases.
    5. Subject with known clinically significant anemia due to iron, vitamin
    B12, or folate deficiencies, or autoimmune or hereditary hemolytic
    anemia, or hypothyroidism, or any type of known clinically significant
    bleeding or sequestration. Subject with drug induced anemia (eg,
    mycophenolate).
    •Iron deficiency to be determined by serum ferritin < 100 μg/L and
    additional testing if clinically indicated (eg, calculated transferrin
    saturation [iron/total iron binding capacity ≤ 20%] or bone marrow
    aspirate stain for iron).
    6. Subject with known history of diagnosis of AML.
    7. Subject receiving any of the following treatment within 8 weeks prior
    to randomization:
    •Anticancer cytotoxic chemotherapeutic agent or treatment
    •Systemic corticosteroid, except for subjects on a stable or decreasing
    dose for ≥ 1 week prior to randomization for medical conditions other
    than MDS
    •Iron-chelating agents, except for subjects on a stable or decreasing
    dose for at least 8 weeks prior to randomization
    •Other RBC hematopoietic growth factors (eg, Interleukin-3)
    •Androgens, unless to treat hypogonadism
    •Hydroxyurea
    •Oral retinoids (except for topical retinoids)
    •Arsenic trioxide
    •Interferon and interleukins
    •Investigational drug or device, or approved therapy for investigational
    use (if 5 times the half-life of the previous investigational drug exceeds
    8 weeks, then the time of exclusion should be extended up to 5 times the
    half-life of the investigational drug)
    8. Subject with uncontrolled hypertension, defined as repeated
    elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or
    diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment.
    9. Subject with any of the following laboratory abnormalities:
    •Absolute neutrophil count (ANC) < 500/μL (0.5 x 10^9/L)
    •Platelet count < 50,000/μL (50 x 10^9/L)
    •Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2
    (Appendix F)
    •Serum aspartate aminotransferase/serum glutamic oxaloacetic
    transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic
    pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
    •Total bilirubin ≥ 2.0 x ULN.
    Higher levels are acceptable if these can be attributed to active red blood
    cell precursor destruction within the bone marrow (ie, ineffective
    erythropoiesis) or in the presence of known history of Gilbert Syndrome.
    10. Subject with prior history of malignancies, other than MDS, unless
    the subject has been free of the disease for ≥ 5 years. However,
    subjects with the following history/concurrent conditions are allowed:
    •Basal or squamous cell carcinoma of the skin
    •Carcinoma in situ of the cervix
    •Carcinoma in situ of the breast
    •Incidental histologic finding of prostate cancer (T1a or T1b using the
    tumor, nodes, metastasis [TNM] clinical staging system)
    Further exclusion criteria are noted in the Protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects who are RBC transfusion free for any 12-week period associated with a concurrent mean hemoglobin increase ≥ 1.5 g/dL compared to baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 1 through Week 24
    E.5.2Secondary end point(s)
    1. Proportion of subjects who are RBC transfusion-free from Week 1
    through Week 24
    2. Mean hemoglobin change over the 24-week period of Week 1 through
    Week 24 compared to baseline
    3. Proportion of subjects achieving HI-E over any consecutive 56-day
    period
    4. Time from first dose to first onset of achieving HI-E
    5. Proportion of subjects who are RBC transfusion-free over a
    consecutive 84-day period
    6. Maximum duration of RBC transfusion independence for subjects who
    achieve RBC-TI ≥ 84 days
    7. Time from first dose to first onset of transfusion independence ≥ 84
    days
    8. Time from first dose to first transfusion on treatment
    9. Total number of RBC units transfused on treatment
    10. Proportion of subjects who are RBC transfusion-free over a
    consecutive 56-day period
    11. Proportion of subjects who are RBC transfusion-free for a
    consecutive 24-week period in the first 48 weeks from first dose
    12. Evaluation of EORTC QLQ-C30 score and FACT-An
    13. Type, frequency, severity of AEs and relationship of AEs to
    luspatercept/epoetin alfa
    14. A Population PK model that describes the PK exposure data of
    luspatercept and associated variability.
    Exposure-response relationship for selected endpoints of efficacy and
    safety
    15. Frequency of antidrug antibodies and effects on efficacy, or safety, or
    PK
    16. Number and percentage of subjects progressing to AML; time to AML
    progression
    17. Time from date of randomization to death due to any cause
    18. Evaluation of biomarkers that may potentially impact luspatercept
    efficacy, predict response or relapse, help to better understand MOA
    and/or provide further prognostic classification of MDS subtypes.
    Molecular markers (eg, SF3B1) include evaluation of MDSassociated
    gene mutations and their impact on drug efficacy, clinical response or
    relapse, drug MOA and prognostication of MDS.
    19. Evaluation of healthcare resource use (eg, hospitalization)
    associated with investigational product (IP) during study
    20. Description of QUALMS-P and Treatment Satisfaction
    E.5.2.1Timepoint(s) of evaluation of this end point
    1, 2, 3, 4, 5, 7, 9, 10: Week 1 through Week 24
    6, 8: Week 1 through End of Treatment
    11, : Week 1 through Week 48
    12, 19, 20: Screening through Week 24
    13: Screening through 42 days post last dose; Randomization through
    Week 48
    14, 15: Randomization through 1 year post first dose
    16, 17: Randomization through 5 years from first dose or 3 years from
    last dose (whichever occurs later)
    18: Baseline through End of Treatment
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers
    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 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 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA111
    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
    Austria
    Belgium
    Canada
    Czech Republic
    France
    Germany
    Italy
    Japan
    Lithuania
    Netherlands
    Poland
    Portugal
    Russian Federation
    Spain
    Sweden
    Switzerland
    Taiwan
    Turkey
    Ukraine
    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
    Either the date of the last visit of the last subject to complete the post-treatement follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date.
    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 years8
    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: 103
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 247
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 255
    F.4.2.2In the whole clinical trial 350
    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)
    Subjects who have received at least one dose of IP should undergo EOT
    & 42-day Follow-up evaluations. In addition, subjects will continue to
    be followed for 5yrs from the date of the first dose of IP, or 3yrs from
    the last dose (which occurs later) unless the subject withdraws from
    the study. For this purpose subjects will be followed-up every 12wks
    for 3yrs from the last dose of IP & every 6 months thereafter, if
    applicable. Subjects will receive SoC post study treatment
    discontinuation.
    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 Decision2018-10-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-26
    P. End of Trial
    P.End of Trial StatusOngoing
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