Clinical Trials Register

Summary
EudraCT Number:	2020-003024-16
Sponsor's Protocol Code Number:	ACT16482
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:	2021-06-04
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-003024-16

A.3

Full title of the trial

Phase 1-2 trial evaluating anti-TGFß agent (SAR439459) or pomalidomide in combination with isatuximab and dexamethasone in relapsed or refractory multiple myeloma (RRMM)

Sperimentazione di fase 1-2 per la valutazione dell’agente anti-TGFß (SAR439459) o pomalidomide in combinazione con isatuximab e desametasone nel mieloma multiplo recidivante o refrattario (MMRR)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Isatuximab in combination with anti-TGFß in RRMM

Isatuximab in combinazione con anti-TGFß nel MMRR

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

ACT16482

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1244-2598

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi S.r.l.
B.5.2	Functional name of contact point	Contact point
B.5.3	Address:
B.5.3.1	Street Address	Viale L. Bodio 37/B
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Isatuximab
D.3.2	Product code	[SAR650984]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Isatuximab
D.3.9.2	Current sponsor code	SAR650984
D.3.9.4	EV Substance Code	SUB119676
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dexamethasone 4 mg JENAPHARM®
D.2.1.1.2	Name of the Marketing Authorisation holder	mibe GmbH Artzneimittel
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Desametasone
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DESAMETASONE
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Dexamethasone Base
D.3.9.4	EV Substance Code	SUB125563
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dexamethasone 8 mg JENAPHARM®
D.2.1.1.2	Name of the Marketing Authorisation holder	mibe GmbH Artzneimittel
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Desametasone
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DESAMETASONE
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Dexamethasone Base
D.3.9.4	EV Substance Code	SUB125563
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Imnovid 4mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Imnovid
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Pomalidomide
D.3.9.4	EV Substance Code	SUB33379
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Imnovid 3mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Imnovid
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Pomalidomide
D.3.9.4	EV Substance Code	SUB33379
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Imnovid 2mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Imnovid
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Pomalidomide
D.3.9.4	EV Substance Code	SUB33379
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 7
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Imnovid 1mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Imnovid
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.2	Current sponsor code	.
D.3.9.3	Other descriptive name	Pomalidomide
D.3.9.4	EV Substance Code	SUB33379
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 8
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	.
D.3.2	Product code	[SAR439459]
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	SAR439459
D.3.9.3	Other descriptive name	SAR439459
D.3.9.4	EV Substance Code	SUB192700
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

Plasma cell myeloma refractory

Mieloma plasmacellulare refrattario

E.1.1.1

Medical condition in easily understood language

Cancer

Cancro

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

•Part 1 (dose escalation Arm B): To determine the recommended dose of SAR439459 when combined with isatuximab ± and dexamethasone in participants with relapsed or refractory multiple myeloma (RRMM).
•Part 2: To demonstrate the clinical benefit of SAR439459 combined with isatuximab and dexamethasone in terms of rate of very good partial response (VGPR) or better.

•Parte 1 (Braccio B incremento della dose): Determinare la dose raccomandata di SAR439459 in combinazione con isatuximab e desametasone in pazienti con mieloma multiplo recidivante o refrattario (MMRR).
•Parte 2: Dimostrare il beneficio clinico di SAR439459 combinato con isatuximab e desametasone in termini di tasso di risposta parziale molto buona (VGPR) o migliore.

E.2.2

Secondary objectives of the trial

To assess the ORR in each treatment arm.
• To assess the clinical benefit rate (CBR) in each treatment arm.
• To assess the duration of response (DOR) in each treatment arm.
• To assess the time to first response (TT1R) in each treatment arm.
• To assess the time to best response (TTBR) in each treatment arm.
• To assess MRD in each treatment arm.
To assess safety and tolerability in each treatment arm.
• To assess progression-free survival (PFS) in each treatment arm.
• To assess overall survival (OS) in each treatment arm.
• To evaluate the potential immunogenicity of isatuximab and SAR439459.
• To characterize the PK of isatuximab and SAR439459 .
• To assess clinical outcome assessments (COAs).
To assess the incidence of skeletal-related events (SREs).
• To assess the time to first occurrence of SRE.
• To assess health care resource utilization related with SREs.

Valutare tasso di risp complessiva (ORR) in ciascun braccio di trattam.
•Valutare tasso di beneficio clinico (CBR) in ciascun braccio di trattam.
•Valutare durata della risp (DOR) in ciascun braccio di trattam.
•Valutare tempo alla prima risp (TT1R) in ciascun braccio di trattam.
•Valutare tempo alla migliore risp (TTBR) in ciascun braccio di trattam.
•Valutare mal.residua minima (MRD) in ciascun braccio di trattam.
Valutare sicurezza e tollerabilità in ciascun braccio di trattam.
•Valutare sopravviv.libera da progress.(PFS) in ciascun braccio di trattam.
•Valutare sopravviv.globale (OS) in ciascun braccio di trattam.
•Valutare l’immunogenicità potenziale di isatuximab e SAR439459
•Caratterizzare farmacocinetica (PK) di isatuximab e di SAR439459
•Valutare le valutazioni di esito clinico (COA)
Valutare l’incidenza di eventi scheletrici-correlati (SRE)
•Valutare il tempo trascorso fino alla prima occorrenza di SRE
•Valutare l’utilizzo delle risorse di assistenza sanitaria correlate a SRE

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Participants who have received at least 3 prior lines of therapy for Multiple myeloma or at least 2 prior lines if at least one of these lines consisted of 2 or more multiagent regimens. Prior exposure to drugs targeting CD38 is allowed with a wash-out of at least 6 months after the last dose.
-Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
-measurable disease.
-Capable of giving signed informed consent.

-Partecipanti che hanno ricevuto almeno 3 precedenti linee di terapia per il MM, o almeno 2 linee precedenti se almeno una di queste linee consisteva in 2 o più regimi multiagente. La precedente esposizione ai farmaci target per CD38 è consentita con un wash-out di almeno 6 mesi dopo l’ultima dose.
- Performance status secondo l’Eastern Cooperative Oncology Group (ECOG) 0-1.
- malattia misurabile.
- In grado di fornire il proprio consenso informato scritto.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
-Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to randomization.
-Uncontrolled or active hepatitis B or C virus.
-Malabsorption syndrome.
-Any anti-MM drug treatment within 14 days before randomization, including dexamethasone.
-Inadequate organ functions.
-Corrected serum calcium >14 mg/dL (>3.5 mmol/L).
-Sensitivity to any of the study interventions.
-Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control.

In presenza di uno dei seguenti criteri i partecipanti saranno esclusi dallo studio:
-Malattia cardiaca clinicamente significativa (compresa quella valvolare) o vasculopatia nei 3 mesi precedenti la randomizzazione
-Infezione da virus dell’epatite B o C non controllata o attiva
-Sindrome da malassorbimento
-Qualsiasi trattamento farmacologico anti-mieloma multiplo entro i 14 giorni prima della randomizzazione, compreso desametasone
-Funzionalità d'organo inadeguata
- Calcio sierico corretto > 14 mg/dl (> 3,5 mmol/l)
- Sensibilità a uno qualsiasi dei trattamenti dello studio
-Donne potenzialmente fertili o partecipanti di sesso maschile con donne potenzialmente fertili che non accettano di utilizzare un metodo di contraccezione altamente efficace

E.5 End points

E.5.1

Primary end point(s)

1. Determination of the recommended dose of SAR439459 in experimental arm
Part 1: (dose escalation arm B):
Determination of the dose will be based on: safety and tolerability in terms of treatment emergent adverse events/serious adverse events (SAEs), dose limiting toxicity occurrence, laboratory Parameters including pharmacokinetic and pharmocodynamic information, vital signs, and findings from physical examination.
2.VGPR Rate (Rate of Very Good Partial Response Rate or Better)
Part 2 (Arm B):
VGPR or better rate is defined as the percentage of participants with a VGPR or better as defined by the 2016 International Myeloma Working Group (IMWG) response criteria, assessed by Investigator based on central laboratory values.

1. Determinazione della dose raccomandata di SAR439459 nel braccio sperimentale
Parte 1 (Braccio B incremento della dose):
La determinazione della dose si baserà su: sicurezza e tollerabilità in termini di eventi avversi emergenti dal trattamento/eventi avversi seri (SAE), insorgenza di tossicità dose-limitante, parametri di laboratorio comprese informazioni su farmacocinetica e farmacodinamica, parametri vitali e risultati dell’esame obiettivo.
2. Tasso di risposta parziale molto buona (VGPR) o migliore
Parte 2 (Braccio B):
Il tasso di VGPR o migliore è definito come la percentuale di partecipanti con VGPR o migliore secondo i criteri di risposta del Gruppo internazionale del mieloma (IMWG) del 2016, valutati dallo sperimentatore in base ai valori del laboratorio centrale.

E.5.1.1

Timepoint(s) of evaluation of this end point

1.Through the end of cycle 1 (approximately 6 weeks)
2.Up to approximately 28 months after the First patient in or scheduled assessment

1.Fino alla fine del Ciclo 1 (circa 6 settimane)
2.Fino a circa 28 mesi dal primo paziente arruolato o valutazione prevista

E.5.2

Secondary end point(s)

1.Overall Response Rate (ORR) in each experimental arm
2.Clinical benefit rate (CBR) in each treatment arm
3.Pharmokinetics (PK) Parameter
4.Incidence of anti drug antibodies (ADAs) for SAR439459 (arm B) and isatuximab (all arms)
5.Duration of Response (DOR) in each treatment arm
6.Time to First Response (TT1R) in each treatment arm
7.Time to Best Response (TTBR) in each treatment arm
8.MRD in each treatment arm
9.Safety and Tolerability in each treatment arm
10.Progression-free survival (PFS) in each treatment arm
11.Overall Survival (OS) in each treatment arm
12.Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
13.Disease- and treatment-related quality of life will be assessed using the EORTC multiple myeloma module (QLQ-MY20) questionnaire
14.Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)
15.The intensity of skeletal-related events (SRE)-related bone pain will be assessed using the skeletal-related bone pain numeric rating scale (SRE-BP-NRS) for control arm and Isa-Dex-Combo anti-TGF ß (SAR439459) arm only
16.Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales
17.SRE Incidence
18.Time to First Occurrence of SRE Assessment
19.Assessment of Health care resource utilization related with SREs

1. Tasso di risposta complessiva (ORR) in ciascun braccio di trattamento.
2. Tasso di beneficio clinico (CBR) in ciascun braccio di trattamento.
3. Parametri di farmacocinetica (PK).
4. Incidenza di anticorpi anti-farmaco (ADA) per SAR439459 (Braccio B) e isatuximab (tutti i bracci).
5. Durata della risposta (DOR) in ciascun braccio di trattamento.
6. Tempo alla prima risposta (TT1R) in ciascun braccio di trattamento.
7. Tempo alla migliore risposta (TTBR) in ciascun braccio di trattamento.
8. MRD in ciascun braccio di trattamento.
9. Sicurezza e tollerabilità in ciascun braccio di trattamento.
10. Sopravvivenza libera da progressione (PFS) in ciascun braccio di trattamento.
11. Sopravvivenza globale (OS) in ciascun braccio di trattamento.
12. Il questionario principale per la qualità della vita (QLQ-C30) dell’European Organisation for Research and Treatment of Cancer (EORTC) sarà utilizzato per valutare la qualità della vita correlata allo stato di salute (HRQL) specifico per la malattia.
13. Il questionario per la qualità della vita per il mieloma multiplo (QLQ-MY20) dell’EORTC sarà utilizzato per misurare la HRQL specifica per il mieloma, per i sintomi correlati alla malattia e al trattamento e per l’impatto dei sintomi.
14. Il Functional Assessment of Cancer Therapy – General (FACT-G) (GP5) sarà utilizzato per valutare l’impatto globale degli effetti collaterali.
15. Sarà utilizzata una scala di valutazione numerica del dolore osseo correlato all’apparato scheletrico (SRE-BP NRS) per valutare l’intensità del dolore osseo correlato all’SRE per il braccio di controllo e per il braccio Isa-Dex-Combo anti-TGF ß (SAR439459).
16. Le scale di Impressione globale della gravità riferita dal paziente (PGIS) e Impressione globale del cambiamento riferita dal paziente (PGIC) saranno utilizzate come punti di ancoraggio per la stima/conferma dei punteggi di cambiamento clinicamente significativo stabiliti per i punteggi inerenti alle COA per ciascun dominio.
17. Incidenza di SRE.
18. Tempo trascorso fino alla prima occorrenza di SRE.
19. Valutazione dell’utilizzo delle risorse di assistenza sanitaria correlate a SRE

E.5.2.1

Timepoint(s) of evaluation of this end point

1.,2.,5.-8., 10.,11. Up to approximately 28 months after the First patient in or scheduled assessment
3.Cycle 1 day 1, Day8, Day15, day 22/29; from Cycle2 to Cycle4 day 1 and day 15 and from Cycle5 and after day 1 only
4.Cycle 1 Day1, Day8, Day15, from Cycle2 and after Day 1 only
09.Baseline to 30 days after last study treatment administration (up to approximately 28 months after first study treatment)
12.-16.,19.On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at End of treatment and at first follow-up visit.
17.,18. Continuous throughout study assessment (up to approximately 28 months

1.,2.,5.-8., 10.,11. Fino a circa 28 mesi dal primo paziente arruolato o valutazione prevista
3.Ciclo 1 Giorno 1, Giorno 8, Giorno 15, Giorno 22/29; dal Ciclo 2 al Ciclo 4 Giorno 1 e Giorno 15 e dal Ciclo 5 in poi solo Giorno 1
4. Ciclo 1 Giorno 1, Giorno 8, Giorno 15, dal Ciclo 2 in poi solo Giorno 1
09.Dal basale a 30 giorni dopo l’ultima somministrazione del trattamento di studio (fino a circa 28 mesi dopo il primo trattamento di studio)
12.-16.,19. Al Giorno 1 Ciclo 1, poi ogni 2 cicli per il primo anno; poi ogni 3 cicli da allora in poi, alla fine del trattamento e alla prima visita di follow-up
17.,18. Con continuità nel corso delle valutazioni dello studio (fino a circa 28 mesi)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

phase I-II study

studio di fase I-II

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

France

Germany

Greece

Italy

Norway

Portugal

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-16

P. End of Trial
P.	End of Trial Status	Ongoing

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