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    The EU Clinical Trials Register currently displays   44051   clinical trials with a EudraCT protocol, of which   7319   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2019-003139-47
    Sponsor's Protocol Code Number:EFC15992
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-15
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-003139-47
    A.3Full title of the trial
    A Phase 3 randomized, open label, multicenter study of isatuximab (SAR650984) in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma
    Studio di fase 3, randomizzato, in aperto, multicentrico di isatuximab (SAR650984) in combinazione con lenalidomide e desametasone rispetto a lenalidomide e desametasone in pazienti con mieloma multiplo non sintomatico ad alto rischio
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Isatuximab in combination with lenalidomide and dexamethasone in high-risk smoldering multiple myeloma
    Isatuximab in combinazione con lenalidomide e desametasone nel mieloma multiplo non sintomatico ad alto rischio
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code numberEFC15992
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1222-7068
    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 SponsorSANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
    B.1.3.4CountryFrance
    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 supportSanofi-Aventis Recherche & Développement
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSANOFI S.p.A.
    B.5.2Functional name of contact pointCONTACT POINT
    B.5.3 Address:
    B.5.3.1Street AddressVIALE L. BODIO 37/B
    B.5.3.2Town/ cityMILANO
    B.5.3.3Post code20158
    B.5.3.4CountryItaly
    B.5.4Telephone number800226343
    B.5.5Fax number0239394168
    B.5.6E-mailinformazioni.medicoscientifiche@sanofi.com
    D. IMP Identification
    D.IMP: 1
    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 Zelvina® 25 mg
    D.2.1.1.2Name of the Marketing Authorisation holderADALVO 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.3.1Product nameLenalidomide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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 Zelvina® 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderADALVO 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.3.1Product nameLenalidomide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Zelvina® 15 mg
    D.2.1.1.2Name of the Marketing Authorisation holderADALVO 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.3.1Product nameLenalidomide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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 Zelvina® 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderADALVO 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.3.1Product nameLenalidomide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Zelvina® 5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderADALVO 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.3.1Product nameLenalidomide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENALIDOMIDE
    D.3.9.1CAS number 191732-72-6
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB25389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIsatuximab
    D.3.2Product code [SAR650984]
    D.3.4Pharmaceutical form Concentrate 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 INNisatuximab
    D.3.9.2Current sponsor codeSAR650984
    D.3.9.4EV Substance CodeSUB119676
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Dexamethasone 4 mg JENAPHARM®
    D.2.1.1.2Name of the Marketing Authorisation holdermibe GmbH Artzneimittel
    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 nameDesametasone
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDESAMETASONE
    D.3.9.2Current sponsor code.
    D.3.9.3Other descriptive nameDEXAMETHASONE BASE
    D.3.9.4EV Substance CodeSUB125563
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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 Dexamethasone 3.3 mg/mL soluzione per iniezione
    D.2.1.1.2Name of the Marketing Authorisation holderhameln pharmaceuticals 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.3.1Product nameDesametasone
    D.3.2Product code [NA]
    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 INNDESAMETASONE
    D.3.9.2Current sponsor code.
    D.3.9.3Other descriptive nameDEXAMETHASONE BASE
    D.3.9.4EV Substance CodeSUB125563
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3300
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 9
    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 AuthorisationItaly
    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 nameMontelukast
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMONTELUKAST
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 10
    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 AuthorisationItaly
    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 nameParacetamolo
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPARACETAMOLO
    D.3.9.2Current sponsor codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 11
    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 AuthorisationItaly
    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 nameOmeprazolo
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOMEPRAZOLO
    D.3.9.2Current sponsor codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 12
    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 AuthorisationItaly
    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 nameClorfenamina
    D.3.2Product code [NA]
    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 INNCLORFENAMINA
    D.3.9.2Current sponsor codeNA
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 13
    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 AuthorisationItaly
    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 namemetilprednisolone
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder and solvent 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 INNMETILPREDNISOLONE
    D.3.9.2Current sponsor codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number62500
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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 Dexamethasone 8 mg JENAPHARM®
    D.2.1.1.2Name of the Marketing Authorisation holdermibe GmbH Artzneimittel
    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 nameDesametasone
    D.3.2Product code [N/A]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDESAMETASONE
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameDEXAMETHASONE BASE
    D.3.9.4EV Substance CodeSUB125563
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    Smoldering Multiple Myeloma
    mieloma multiplo non sintomatico.
    E.1.1.1Medical condition in easily understood language
    Cancer
    Cancro.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10035226
    E.1.2Term Plasma cell myeloma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - Safety run-in: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM).
    - Randomized Phase 3: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMM
    - Run-in di sicurezza: Confermare la dose raccomandata di isatuximab in combinazione con lenalidomide e desametasone in partecipanti con mieloma multiplo non sintomatico (SMM) ad alto rischio
    - Fase 3 randomizzata: Dimostrare il beneficio clinico di isatuximab in combinazione con lenalidomide e desametasone nel prolungamento della sopravvivenza libera da progressione rispetto a lenalidomide e desametasone in soggetti con SMM ad alto rischio
    E.2.2Secondary objectives of the trial
    Safety run-in:
    - To assess overall response rate (ORR).
    - To assess duration of response (DOR)
    - To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR)
    - To assess time to diagnostic (SLiM CRAB) progression or death
    - To assess time to first-line treatment for multiple myeloma (MM)
    - To assess the potential immunogenicity of isatuximab.
    - Impact of abnormal cytogenetic subtype
    Randomized Phase 3 - Key Secondary Objectives:
    - To compare between the arms:
    * MRD negativity
    * Sustained MRD negativity
    * Second progression-free survival (PFS2)
    * Overall survival
    Other Secondary Objectives:
    - To evaluate in both arms:
    * CR rate
    * ORR
    * DOR
    * Time to diagnostic (SLiM CRAB) progression
    * Time to first-line treatment for MM
    * Safety and tolerability
    * Pharmacokinetics (PK)
    * Potential of isatuximab immunogenicity
    * Clinical outcome assessments (COAs).
    Run-in di sicurezza:
    -Valutare il tasso di risposta complessiva (ORR).
    -Valutare la durata della risposta (DOR)
    -Valutare la negatività della malattia minima residua (MRD) nei partecipanti che ottengono una risposta parziale molto buona (VGPR) o una risposta completa (CR)
    -Valutare il tempo alla progressione diagnostica (SLiM CRAB) o al decesso
    -Valutare il tempo al trattamento di prima linea per il Mieloma Multiplo (MM)
    -Valutare la potenziale immunogenicità di isatuximab
    -Impatto del sottotipo citogenetico anomalo
    Fase 3 randomizzata-Obiettivi secondari chiave:
    -Per confrontare i 2 bracci:
    Negatività MRD
    Negatività MRD sostenuta
    Sopravvivenza libera da seconda progressione (PFS2)
    Sopravvivenza complessiva
    Altri obiettivi secondari:
    -Da valutare in entrambi i bracci:
    Tasso di CR
    ORR
    DOR
    SLiM CRAB
    Tempo al trattamento di prima linea per il MM
    Sicurezza e tollerabilità
    Farmacocinetica (PK)
    Potenziale di immunogenicità di isatuximab
    Valutazioni degli esiti clinici (COA).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group [IMWG] criteria), defined as serum M-protein >/=30 g/L or urinary M-protein >/=500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to <60%, and absence of myeloma defining events or other related conditions and with high-risk SMM.
    - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2.
    - Capable of giving voluntary written informed consent
    - Partecipante a cui viene diagnosticato entro 5 anni SMM (secondo i criteri del gruppo di lavoro internazionale sul mieloma IMWG), definito come: proteina M sierica >/= 30 g/L o proteina M urinaria >/= 500 mg per 24 ore o entrambe; e/o plasmacellule del midollo osseo clonali (BMPC) dal 10% a <60%, e assenza di eventi che definiscono un mieloma o altre condizioni correlate e con SMM ad alto rischio.
    - Stato di validità secondo l’Eastern Cooperative Oncology Group (ECOG) 0 o 1 o 2.
    - In grado di fornire un consenso informato scritto volontario
    E.4Principal exclusion criteria
    -Evidence of any of the following CRAB criteria or Myeloma Defining Events(SLiM CRAB)detailed below attributable to the particip.SMM involvement
    Increased Ca levels:Corrected serum Ca>1mg/dL above ULN or >11mg/dL
    Renal insufficiency:Determined by GFR<40mL/min/1.73m² (Modification of Diet in Renal Disease[MDRD]Formula) or serum creatinine>2mg/dL
    Anemia(hemoglobin 2g/dL below LLN or <10g/dL or both)transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
    >= 1 bone lytic lesion
    BMPCs>=60%
    Serum involved/uninvolved FLC ratio>=100
    WB-MRI or PET-CT with more than 1 focal lesion(>=5mm in diameter by MRI)
    -Primary systemic amyloid light-chain amyloidosis,MGUS,standard risk smoldering myeloma,soft-tissue plasmacytoma,symptomatic myeloma
    -Uncontroll.infect.within 28 days prior to random.in Ph.3 or 1st study interv. admin. in safety run-in
    -Clinically signific.cardiac or vascular dis. within 3 months prior to random., e.g.Myocardial Infarction;Unstable Angina;Coronary(e.g. Coronary Artery Bypass Graft,Percutaneous Coronary Intervention)or peripheral artery revascularization,Left Ventricular Ejection Fraction<40%,Heart Failure NYHA III-IV,Stroke,Transient Ischemic Attack,Pulmonary Embolism,other thromboembolic event,cardiac arrhythmia(Grade 3 or higher by NCI-CTCAE Ver.5.0)
    -Known AIDS-related illness or known HIV dis. requiring antiviral treatm. or active hepatitis A(defined as positive HA antigen or posit.IgM).HIV serology at screen.will be tested for German particip.and any other country where required as per local regul.and serology hepatitis B and C at screen.will be tested for all particip.
    -Uncontroll.or active HBV infection:Patients with posit.HBsAg and/or HBV DNA
    Note:
    ·Patient can be eligible if anti-HBc IgG posit.(with or without posit.anti-HBs)but HBsAg and HBV DNA are negat.If anti-HBV therapy in relation with prior infect.was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatm.period
    ·Patients with negat.HBsAg and posit.HBV DNA observed during screen.period will be evaluated by a specialist for start of anti-viral treatm:study treatm.could be proposed if HBV DNA becomes negat.and all the other study criteria are still met.
    -Active HCV infect.:posit.HCV RNA and negat.anti-HCV
    Note:
    ·Patients with antiviral therapy for HCV started before initiation of IMP and posit.HCV Ab are eligible.The antiviral therapy for HCV should continue throughout the treatm.period until seroconversion.
    ·Patients with posit.anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible
    -Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide
    -Any of the following within 3 months prior to random.(or 1st study interv.admin. in safety run-in cohort):treatment resistant peptic ulcer disease,erosive esophagitis or gastritis,infectious or inflammatory bowel disease,diverticulitis,pulmonary embolism or other uncontrolled thromboembolic event
    -Received treatm.(eg surgery,radiotherapy,medication) for a malignancy within 3 years of random.(or 1st study interv.admin. in safety run-in cohort)
    -Prior exposure to approved or investigational treatm. for SMM or MM(including but not limited to conventional chemotherapies,immunomodulatory imid drugs or Proteasome inhibitors); concurrent use of bisphosphonates or RANKL inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year IV bisphosphonate given for the treatm.of osteoporosis is permitted
    -Ongoing treatm.with corticosteroids with a dose>10mg prednisone or equivalent per day at the time of random.(or 1st study interv.admin. in safety run-in cohort)
    -Women of childbear.poten. or male particip.with women of childbear.poten. who do not agree to use a highly effective method of birth control
    -Vaccination with live vaccine 4weeks before start of study drug. Seasonal flu vaccines that don't contain live virus are permitted
    -Evid di 1 dei seguenti criteri CRAB o SLiM CRAB attribuibili al coinvolgim dei pz in termini di SMM:
    Aumento livelli di Ca:Ca sierico corretto>1mg/dl al di sopra dell’ULN o>11mg/dl
    Insuff renale:GFR<40ml/min/1,73m²(formula della modifica della dieta nella malattia renale[MDRD])o creatinina sierica>2mg/dl
    Non consentito supporto trasfus.per anemia(Hb 2 g/dl inferiore al LLN o< 10g/dl o entrambi) o trattam.concomitante con agenti stimolanti eritropoietina
    >= 1 lesione litica ossea
    BMPC>=60%
    Rapporto FLC coinvolte/non coinvolte nel siero>=100
    WB-RM o PET-TC con più di 1 lesione focale(>=5mm di diametro mediante RM)
    -Amiloidosi sistemica primaria da catena leggera amiloide,MGUS,mieloma non sintom a rischio std,plasmocitoma dei tessuti molli,mieloma sintom
    -Infez non controll nei28gg preced random nella fase3 o 1a sommin del trattam.di studio nella fase di run-in di sicurezza
    -Mal.cardiaca o vascolare clinicam.significat.nei 3 mesi preced.random.,es.:infarto miocardio;angina instabile;rivascolarizz.arteria coronaria(es.bypass arteria coron,interv.coronarico percutaneo)o periferica,fraz.di eiez.ventric.sx<40%,insuff.cardiaca di classe NYHA III-IV,ictus,attacco ischem transit,embolia polmon,altro evento tromboembolico,aritm cardiaca(Gr.3 o > secondo NCI CTCAE V5.0)
    -Mal.correlata a AIDS o mal.da HIV nota che richieda trattam.antivirale o infez.attiva da epatite A(antig.HA posit o IgM posit).Sierologia HIV allo screen. per i partecip.tedeschi e di qualsiasi altro Paese ove richiesto in conformità alle norm.locali. Sierologia epatite B e C allo screen.sarà esaminata per tutti i partecip.
    -Infez.da HBV non controll o attiva:Pz con positività di HBSag e/o DNA di HBV
    NB:
    Pz idoneo se posit a IgG anti-HBc(con o senza anti-HBs posit)ma HBsAg e DNA di HBV negat.Se la terapia anti-HBV in relazione all’infez preced è stata avviata prima dell’inizio dell’IMP,la terapia anti-HBV e il monitoraggio dovranno continuare per tutto il periodo di trattam.dello studio
    Pz con HBsAg negat e DNA di HBV posit osservato durante lo screen.saranno valutati da uno specialista per l’inizio del trattam.anti-virale:il trattam.dello studio potrebbe essere proposto se DNA di HBV diventa negat e tutti gli altri criteri dello studio sono ancora soddisfatti
    -Infez.attiva da HCV:RNA di HCV posit e anti HCV negat
    NB:
    Idonei i pz con terapia antivir.per HCV preced.inizio dell’IMP e con anticorpi HCV posit.La terapia antivir.per HCV dovrà proseguire per tutto il periodo di trattam.fino alla sieroconversione.
    Idonei i pz con anti-HCV posit. e RNA di HCV non rilevabile senza terapia antivir.per HCV
    -Sindrome da malassorbim o qualsiasi condiz che precluda significativam l’assorbim del lenalidomide
    -1 delle seguenti condiz.entro 3 mesi prima della random.(o 1a sommin.del trattam.dello studio nella coorte di run-in di sicurezza):ulcera peptica resist al trattam.,esofagite o gastrite erosiva,mal.infett. o infiamm.intestinale,diverticolite,embolia polmon o altro evento tromboembolico non controll.
    -Trattam.ricevuto(es:interv chirurgico,radioterap,farm)per tumore maligno entro 3aa dalla random.(o 1a sommin.del trattam.dello studio nella coorte di run-in di sicurezza)
    -Preced.esposiz.a trattam.approvati o speriment.per SMM o MM(inclusi ma non limitati a chemioter convenz,farmaci immunomodulat IMiD o inibit del proteasoma)Non è consentito uso concomitante di bifosfonati o dell’inibitore di RANKL denosumab;tuttavia bisfosfonati preced.o bifosfonati somministrati EV 1 volta/anno per osteoporosi sono consentiti
    -Trattam.in corso con corticosteroidi con dose>10 mg di prednisone o equival al gg al momento della random.(o 1a sommin.del trattam.dello studio nella coorte di run-in di sicurezza)
    -Donne in età fertile o uomini con donne in età fertile che non accettano di utilizzare un metodo di controllo delle nascite altam efficace
    -Vaccin.con vaccino vivo 4settim.prima dell’inizio del farmaco di studio.Vacc.antinfluenzali stagionali che non contengono virus vivo sono consentiti
    E.5 End points
    E.5.1Primary end point(s)
    1. Safety assessment: adverse events (AEs): Number of participants with AEs
    2. Plasma concentration of isatuximab (Cmax): Maximum concentration observed after the first infusion
    3. Receptor density/receptor occupancy (safety run-in): Change in CD38 receptor occupancy from baseline
    4. Progression-free survival (PFS) (Randomized Phase 3): Time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee assessment according to 2014 International Myeloma Working Group criteria or death from any cause, whichever happens first.
    1.Valutazione della sicurezza: eventi avversi (AEs): numero di pazienti con eventi avversi
    2.Concentrazione plasmatica di isatuximab (Cmax): Massima concentrazione osservata dopo la prima infusione
    3.Densità del recettore/ occupazione del recettore (Run-in di sicurezza): modifica dell’occupazione del recettore CD38 dal basale
    4.Sopravvivenza libera da progressione (PFS) (Fase 3 randomizzata): tempo dalla randomizzazione a MM (criteri SLiM CRAB) o altre condizioni correlate basate sulla valutazione IRC secondo i criteri dell’International Myeloma Working Group (IMWG) del 2014 o il decesso per qualsiasi causa, a seconda di quale evento si verifichi per primo
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Baseline to 30 days after last study treatment administration (up to approximately 100 months after first study treatment).
    2. Up to approximately 24 months
    3. Baseline to Cycle 2 Day 1 (each cycle is 28 days)
    4. Up to approximately 85 months
    1.Dalla Baseline a 30 giorni dopo l'ultima somministrazione del trattamento in studio (fino a circa 100 mesi dopo il primo trattamento di studio).
    2.Fino a circa 24 mesi
    3.Dalla Baseline al ciclo 2 giorno 1 (ogni ciclo è di 28 giorni)
    4.Fino a circa 85 mesi.
    E.5.2Secondary end point(s)
    1. Overall response rate (ORR): Proportion of participants with best overall response recorded as partial response or better according to 2016 IMWG criteria.
    2. Duration of response (DOR): Time from the date of the first response to date of progressive disease or death, whichever happens first
    3. Minimal residual disease (MRD) negativity: Number of participants for whom MRD is negative
    4. Time to diagnostic (SLiM CRAB) progression or death: Time from randomization to diagnosis of SLiM-CRAB or other related conditions, progression, or death from any cause
    5. Time to first-line treatment for multiple myeloma (MM): Time from randomization to first-line treatment for MM
    6. Immunogenicity: Incidence of anti-drug antibodies (ADA): Number of participants with anti-drug antibodies against isatuximab
    7. Sustained MRD negativity: Number of participants with sustained MRD negativity (sample is still negative at least 1 year after the first negativity assessment)
    8. Second PFS (PFS2): Time from randomization to date of second objective progressive disease or death from any cause
    9. Overall survival: Time from date of randomization to death from any cause
    10. Complete response rate: Percentage of particpants with a CR as defined by 2016 IMWG response criteria
    11. Safety assessment: adverse events (AEs): Number of participants with AEs
    12. Plasma concentration of isatuximab: Maximum concentration observed after the first infusion (Cmax)
    13. European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30: Mean change from baseline scores will be assessed, with responses ranging from 1=not at all to 4=very much or 1=very poor to 7=excellent; higher scores represent a better level of physical functioning
    14. EORTC QLQ-MY20: Mean change from baseline in scores will be assessed using a 4-point scale, with responses ranging from 1=not at all to 4=very much; higher scores represent better perspectives of the future and higher level of symptomatology
    15. EQ-5D-5L: Mean change from baseline scores will be assessed from 5 items, with responses ranging from 'no' to 'extreme problems'; health state utility values (HSUVs) are generated by multiplying the item scores by country specific value sets; health status is assessed via a VAS; higher scores = higher HSUV/health status
    16. Economic questionnaire: Mean change from baseline scores will assess work productivity, resource utilization and working days missed by a caregiver; higher scores = greater impact on work/productivity, resources
    17. Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2): Patient's qualitative assessment of treatment will be assessed using a 10 point VAS/NRS scale with response anchors of 'not beneficial at all' to 'extremely beneficial'; higher scores represent greater patient-perceived benefits of treatment
    1. Tasso di risposta complessiva (ORR): percentuale di partecipanti con migliore risposta complessiva registrata come risposta parziale o migliore in base ai criteri IMWG del 2016.
    2. Durata della risposta (DOR): il tempo dalla data della prima risposta alla data della prima progressione di malattia o di decesso, a seconda di quale circostanza si verifichi per prima
    3. Negatività della malattia minima residua (MRD): numero di partecipanti per i quali la MRD è negativa
    4. Tempo alla progressione diagnostica (SLiM CRAB) o al decesso: tempo dalla randomizzazione alla diagnosi di SLiM CRAB o di altre condizioni correlate, progressione, oppure al decesso per qualsiasi causa
    5. Tempo al trattamento di prima linea per il mieloma multiplo (MM): tempo dalla randomizzazione al trattamento di prima linea per il MM
    6. Immunogenicità: Incidenza di anticorpi anti-farmaco (ADA): numero di pazienti con anticorpi anti-farmaco contro isatuximab
    7. Negatività MRD sostenuta: numero di partecipanti per i quali la MRD è negativa (campione è ancora negativo almeno 1 anno dopo la prima valutazione della negatività)
    8. PFS secondaria (PFS2): l’intervallo dalla data della randomizzazione alla data della seconda progressione di malattia o decesso per qualsiasi causa
    9. Sopravvivenza complessiva: tempo trascorso dalla randomizzazione al decesso per qualsiasi causa.
    10. Tasso di risposta completo: percentuale di partecipanti con una CR secondo quanto definito dai criteri di risposta IMWG del 2016
    11. Valutazione della sicurezza: eventi avversi (AE): numero di partecipanti con AE
    12. Concentrazione plasmatica di isatuximab: concentrazione massima osservata dopo la prima infusione (Cmax)
    13. EORTC QLQ-C30: Sarà valutata la variazione media rispetto ai punteggi alla baseline, con risposte che vanno da 1 = per niente a 4 = molto o 1 = molto scarso a 7 = eccellente; i punteggi più alti rappresentano un migliore livello di funzionamento fisico
    14. EORTC QLQ-MY20: La variazione media nei punteggi dalla baseline sarà valutato usando una scala a 4 punti, con risposte che vanno da 1 = per niente a 4 = molto; i punteggi più alti rappresentano le migliori prospettive per il futuro e livello più elevato di sintomatologia
    15. EQ-5D-5L: La variazione media rispetto ai punteggi della baseline verrà valutata da 5 elementi, con risposte che vanno dal "no" ai "problemi estremi"; i valori di utilità dello stato di integrità (HSUV) vengono generati moltiplicando i punteggi degli item per set di valori specifici per paese; lo stato di salute è valutato tramite VAS; punteggi più alti = HSUV/stato di salute più elevati
    16. Questionario economico: variazione media rispetto ai punteggi della baseline valuterà la produttività lavorativa, l'utilizzo delle risorse e i giorni lavorativi persi da un caregiver; punteggi più alti = maggiore impatto sul lavoro/produttività, risorse
    17. Valutazione qualitativa del trattamento del paziente versione 2 (PQAT-v2): La valutazione qualitativa del trattamento del paziente sarà valutata usando una scala 10 punti VAS/NRS con ancore di risposta di 'non benefico' a estremamente utile'; punteggi più alti rappresentano una maggiore beneficio del trattamento percepito dal paziente
    E.5.2.1Timepoint(s) of evaluation of this end point
    1, 2, 3, 4, 5, 7, 10: Up to approximately 85 months.
    6, 12: Up to approximately 24 months
    8: Up to approximately 120 months
    9: Up to approximately 144 months
    11: Baseline to 30 days after last study treatment administration (up to approximately 100 months after first study treatment)
    13, 14, 15, 16: Baseline to follow-up (up to approximately 10 years)
    17: End of treatment (up to approximately 10 years)
    1, 2, 3, 4, 5, 7, 10: Fino a circa 85 mesi.
    6, 12: Fino a circa 24 mesi
    8: Fino a circa 120 mesi
    9: Fino a circa 144 mesi
    11: Baseline a 30 giorni dopo l'ultima somministrazione del trattamento in studio (fino a circa 100 mesi dopo il primo trattamento in studio)
    13, 14, 15, 16: Baseline a follow-up (fino a circa 10 anni)
    17: Fine del trattamento (fino a circa 10 anni).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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 EEA62
    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 Information not present in EudraCT
    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
    Brazil
    Canada
    China
    Israel
    Japan
    Korea, Republic of
    New Zealand
    Turkey
    United States
    Denmark
    France
    Germany
    Greece
    Hungary
    Ireland
    Italy
    Lithuania
    Norway
    Poland
    Spain
    Sweden
    United Kingdom
    Czechia
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years13
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years13
    E.8.9.2In all countries concerned by the trial months3
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 300
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 275
    F.4.2.2In the whole clinical trial 500
    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
    nessuno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-04-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-05
    P. End of Trial
    P.End of Trial StatusOngoing
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