Clinical Trials Register

Summary
EudraCT Number:	2020-002700-39
Sponsor's Protocol Code Number:	CBAF312D2301
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-23
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

Spain - AEMPS

A.2

EudraCT number

2020-002700-39

A.3

Full title of the trial

A 2-year randomized, 3-arm, double-blind, non-inferiority study comparing the efficacy and safety of ofatumumab and siponimod versus fingolimod in pediatric patients with multiple sclerosis followed by an open-label extension. Additional PIP decision number: P/014/2021

Estudio de no inferioridad, aleatorizado, doble ciego, con tres brazos y de 2 años de duración en el que se compara la eficacia y la seguridad de ofatumumab y siponimod frente a fingolimod en pacientes pediátricos con esclerosis múltiple, seguido de una extensión abierta. Número de decisión adicional de PIP: P/014/2021

A.3.1

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

Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis.

Eficacia y seguridad de ofatumumab y siponimod, en comparación con fingolimod, en pacientes pediátricos con esclerosis múltiple.

A.3.2

Name or abbreviated title of the trial where available

NEOS

A.4.1

Sponsor's protocol code number

CBAF312D2301

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/042/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Farmacéutica S.A.
B.1.3.4	Country	Spain
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica S.A.
B.5.2	Functional name of contact point	Trial Monitoring Organization (TMo)
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34900353036
B.5.5	Fax number	+34932479903
B.5.6	E-mail	eecc.novartis@novartis.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	Yes
D.2.1.1.1	Trade name	Kesimpta
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Ireland Limited
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	ofatumumab
D.3.2	Product code	OMB157
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OFATUMUMAB
D.3.9.1	CAS number	679818-59-8
D.3.9.2	Current sponsor code	OMB157
D.3.9.4	EV Substance Code	SUB25221
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	50
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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	Mayzent
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.2	Product code	BAF312
D.3.4	Pharmaceutical form	Film-coated 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	Siponimod
D.3.9.1	CAS number	1234627-85-0
D.3.9.2	Current sponsor code	BAF312
D.3.9.3	Other descriptive name	SIPONIMOD FUMARIC ACID
D.3.9.4	EV Substance Code	SUB193903
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Siponimod
D.3.2	Product code	BAF312
D.3.4	Pharmaceutical form	Film-coated 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	Siponimod
D.3.9.1	CAS number	1234627-85-0
D.3.9.2	Current sponsor code	BAF312
D.3.9.3	Other descriptive name	SIPONIMOD FUMARIC ACID
D.3.9.4	EV Substance Code	SUB193903
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Siponimod
D.3.2	Product code	BAF312
D.3.4	Pharmaceutical form	Film-coated 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	Siponimod
D.3.9.1	CAS number	1234627-85-0
D.3.9.2	Current sponsor code	BAF312
D.3.9.3	Other descriptive name	SIPONIMOD FUMARIC ACID
D.3.9.4	EV Substance Code	SUB193903
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	0.5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Mayzent
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.2	Product code	BAF312
D.3.4	Pharmaceutical form	Film-coated 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	Siponimod
D.3.9.1	CAS number	1234627-85-0
D.3.9.2	Current sponsor code	BAF312
D.3.9.3	Other descriptive name	SIPONIMOD FUMARIC ACID
D.3.9.4	EV Substance Code	SUB193903
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	0.25
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Siponimod
D.3.2	Product code	BAF312
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Yes
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	Siponimod
D.3.9.1	CAS number	1234627-85-0
D.3.9.2	Current sponsor code	BAF312
D.3.9.3	Other descriptive name	SIPONIMOD FUMARIC ACID
D.3.9.4	EV Substance Code	SUB193903
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	0.1
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Gilenya
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd.
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.3.2	Product code	FTY720
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	fingolimod
D.3.9.1	CAS number	162359-56-0
D.3.9.2	Current sponsor code	FTY720
D.3.9.3	Other descriptive name	FINGOLIMOD HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB30967
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	0.5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Gilenya
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd.
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.3.2	Product code	FTY720
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	fingolimod
D.3.9.1	CAS number	162359-56-0
D.3.9.2	Current sponsor code	FTY720
D.3.9.3	Other descriptive name	FINGOLIMOD HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB30967
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	0.25
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled pen
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 4
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Multiple Sclerosis in pediatric patients

Esclerosis múltiple en pacientes pediátricos

E.1.1.1

Medical condition in easily understood language

Multiple Sclerosis in children

Esclerosis múltiple en niños

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the non-inferiority of ofatumumab and/or siponimod as compared to fingolimod as assessed by annualized relapse rate (ARR) in the target pediatric MS participants treated for up to 2-years

Demostrar la no inferioridad de ofatumumab y/o siponimod en comparación con fingolimod en la tasa anualizada de brotes (TAB) en los participantes diana pediátricos con EM tratados hasta 2 años.

E.2.2

Secondary objectives of the trial

-Key secondary objective: To demonstrate the superiority of ofatumumab and/ or siponimod as compared to historical interferon beta-1a data, assessed by annualized relapse rate (ARR)
-To evaluate the effects of ofatumumab and/or siponimod versus fingolimod on the number of new or newly enlarging T2 lesions
- To evaluate the effects of ofatumumab and/or siponimod versus fingolimod on neurofilament light chain (NfL) concentrations
- To evaluate the pharmacokinetic (PK) properties of ofatumumab and siponimod (and its metabolite M17) in pediatric MS patients
- To evaluate immunogenicity (ofatumumab)
- To evaluate the safety and tolerability of ofatumumab and siponimod

- Objetivo secundario clave: Demostrar la superioridad de ofatumumab y/o siponimod en comparación con los datos históricos de interferón beta-1a, evaluado mediante la tasa anualizada de brotes (TAB).
-Evaluar los efectos de ofatumumab y / o siponimod versus fingolimod en el número de lesiones nuevas o preexistentes aumentadas en T2
- Evaluar los efectos de ofatumumab y / o siponimod versus fingolimod en las concentraciones de cadenas ligeras de neurofilamentos (NfL)
- Evaluar las propiedades farmacocinéticas (PK) de ofatumumab y siponimod (y su metabolito M17) en pacientes pediátricos con EM.
- Evaluar la seguridad y la tolerabilidad de ofatumumab y siponimod.
- Evaluar la inmunogenicidad (ofatumumab).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Signed informed consent/assent must be obtained prior to participation in the study
-Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
-A diagnosis of MS as defined by the consensus definition for pediatric MS
-Expanded Disability Status Scale (EDSS) score of 0 to 5.5 (inclusive) at screening
-At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior to screening or evidence of one or more new T2 lesions compared to prior MRI conducted within 12 months prior to randomization (including screening MRI) or one or more Gd-enhancing
T1 lesions on MRI conducted within 12 months prior to randomization
-Other protocol-defined inclusion/exclusion criteria may apply

- Se deberá obtener el consentimiento/asentimiento informado
firmado antes de la participación en el estudio.
- Entre 10 y <18 años de edad (es decir, todavía no tienen 18 años) en
la aleatorización.
- Un diagnóstico de EM según la definición de consenso para EM
pediátrica.
- Puntuación de la Expanded Disability Status Scale (EDSS) de 0 a
5,5 (ambas incluidas) en la selección.
- Al menos un brote/ataque de EM durante el año previo o dos brotes
de EM en los dos años anteriores a la selección o evidencia de una
o más lesiones nuevas en T2 en comparación con la RM anterior
realizada durante los 12 meses anteriores a la aleatorización
(incluida la RM de selección) o una o más lesiones captantes de Gd
en T1 en la RM realizada durante los 12 meses anteriores a la
aleatorización.
-Pueden aplicarse otros criterios de inclusión / exclusión definidos por el protocolo

E.4

Principal exclusion criteria

-Participants with progressive MS
-Participants meeting the definition of ADEM
-Participants meeting criteria for neuromyelitis optica or tested positive for aquaporin 4 (AQP4) at Screening
-Participants tested positive for anti-MOG at Screening
-Participants with widespread and symmetric white matter alterations in the Screening MRI suggestive of other demyelinating disorders (e.g. metabolic disorders, mitochondrial disorders)
-Homozygosity for CYP2C9*3, or refusal to test for CYP2C9
-Participants with an active, chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. Sjögren’s disease, systemic lupus erythematosus) or with a known immunodeficiency syndrome (Acquired immunodeficiency syndrome (AIDS), hereditary immunodeficiency, drug-induced immunodeficiency ) or tested positive for HIV at Screening
-Participants with neurological symptoms consistent with progressive multifocal leukoencephalopathy (PML) or confirmed PML
-Participants diagnosed with macular edema during the Screening period
-Participants with severe active systemic bacterial, viral or fungal infections, including tuberculosis
-Participants with any severe cardiac disease or significant findings on the screening ECG
-Any history of malignancy of any organ system
-Participants treated with any of the listed medication as Exclusion Medication within defined timespan
-Positive results of screening period testing for serological markers for hepatitis A, B, C and E indicating acute or chronic infection
-Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function
-Have received any live or live-attenuated vaccines (including for varicellazoster virus or measles) within 4 weeks prior to first study drug administration
-Participants without acceptable evidence of immunity to varicella-zoster virus, mumps, measles, rubella, diphtheria, tetanus and pertussis at Randomization
-Participants with any other significant condition, as assessed by the investigator, which may preclude participant from participating in the study.
-Pregnant or nursing (lactating) female participant
-other protocol-defined inclusion/exclusion criteria may apply

- Participantes con EM progresiva.
- Participantes que cumplan la definición de ADEM por sus siglas en
inglés.
- Participantes que cumplan los criterios de neuromielitis óptica o den
positivo en acuaporina 4 (ACP4) en la selección.
- Participantes que den positivo en anti-MOG en la selección.
- Participantes con alteraciones generalizadas y simétricas de la
materia blanca en la RM de la selección que parezcan indicar otros
trastornos desmielinizantes (p. ej., trastornos metabólicos o
trastornos mitocondriales).
- Homocigosidad de CYP2C9 * 3, o rechazo a realizar la prueba de
CYP2C9.
- Participantes con una enfermedad crónica activa (o estable, pero
tratada con inmunoterapia) del sistema inmunitario que no sea EM
(p. ej., enfermedad de Sjögren, lupus eritematoso sistémico) o con
un síndrome de inmunodeficiencia conocido (síndrome de
inmunodeficiencia adquirida [SIDA], inmunodeficiencia hereditaria,
inmunodeficiencia inducida por fármaco) o que hayan dado positivo
a VIH en la selección.
- Participantes con síntomas neurológicos que coincidan con la leucoencefalopatía multifocal progresiva (LMP) o con LMP
confirmada.
- Participantes con diagnóstico de edema macular durante el periodo
de selección.
- Participantes con infecciones bacterianas, víricas o por hongos
activas y graves, incluida la tuberculosis.
- Participantes con cualquier enfermedad cardíaca grave o hallazgos
significativos en el ECG de la selección.
- Antecedentes de tumor maligno de cualquier sistema orgánico.
- Participantes tratados con alguno de los medicamentos excluidos
durante el periodo definido.
- Resultados positivos del periodo de selección en la prueba de
marcadores serológicos de hepatitis A, B, C y E que indican una
infección aguda o crónica.
- Cualquier otra evaluación de laboratorio clínicamente significativa
según lo determinado por el investigador (p. ej., anemia,
neutropenia, trombocitopenia, signos de deterioro de la función de la
médula ósea).
- Pacientes que hayan recibido cualquier vacuna viva o viva-atenuada
(incluida la del virus de la varicela-zóster o del sarampión) durante
las 4 semanas anteriores a la primera administración del fármaco del
estudio.
- Participantes sin evidencia aceptable de inmunidad al virus de la
varicela-zóster, paperas, sarampión, rubeola, difteria, tétanos y tos
ferina en la aleatorización.
- Participantes con cualquier otra enfermedad significativa, según el
investigador, que pueda impedir que participen en el estudio.
- Participantes embarazadas o en periodo de lactancia.
-Pueden aplicarse otros criterios de inclusión / exclusión definidos por el protocolo

E.5 End points

E.5.1

Primary end point(s)

Annualized relapse rate (ARR of confirmed relapses)

Tasa anualizada de brotes (TAB de brotes confirmados)

E.5.1.1

Timepoint(s) of evaluation of this end point

participants treated up to 2-years

participantes tratados hasta 2 años

E.5.2

Secondary end point(s)

-Annualized relapse rate (ARR of confirmed relapses)
-Number of new or newly enlarging T2 lesions on MRI per year (annualized T2 lesion rate)
-Neurofilament light chain (NfL) concentration in serum
-Ofatumumab and siponimod and(metabolite M17) plasma concentrations
-Proportion of participants with antiofatumumab antibodies
-Adverse events, Columbia Suicide Severity Rating Scale (C-SSRS), ECG, laboratory and ophthalmological data, pulmonary function tests and vital signs

- Tasa anualizada de brotes (TAB de brotes confirmados)
-Número de lesiones nuevas o preexistentes aumentadas en T2 en la resonancia magnética por año (tasa anualizada de lesiones T2)
-Concentraciones de cadenas ligeras de neurofilamentos (NfL) en suero
-Concentraciones plasmáticas de ofatumumab y siponimod y (metabolito M17)
-Proporción de participantes con anticuerpos antiofatumumab
-Eventos adversos, Columbia Suicide Severity Rating Scale (C-SSRS), ECG, datos de laboratorio y oftalmológicos, pruebas de función pulmonar y signos vitales

E.5.2.1

Timepoint(s) of evaluation of this end point

For the key secondary endpoint ARR, the endpoint is for participants treated up to 2-years. Information for the timepoints for other secondary endpoints can be found in the study protocol

Para el objetivo secundario principal TAB, el criterio de valoración es para los participantes tratados hasta 2 años. La información para los tiempos de los otros objetivos secundarios se puede encontrar en el protocolo del estudio.

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tolerancia

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

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

Brazil

Canada

Chile

Guatemala

India

Israel

Mexico

Russian Federation

Serbia

Taiwan

Turkey

Ukraine

United States

Austria

Belgium

Croatia

Estonia

France

Germany

Italy

Latvia

Lithuania

Poland

Portugal

Romania

Slovakia

Spain

United Kingdom

Czechia

Argentina

E.8.7

Trial 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

The end of the clinical trial is defined as the last visit of the last participant or at a later point in time as defined by the protocol

El final del ensayo clínico se define como la última visita del último participante o en un momento posterior según lo definido por el protocolo.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

180

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

170

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minor patients aged 10 to less than 18 years : parents or guardian must give their written consent.

Los pacientes menores de entre 10 y 18 años: los padres o tutores deben dar su consentimiento por escrito.

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

180

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)

Participants who complete the Core Part Treatment period will be invited to participate in the Extension Part. In the open label Extension Part, participants will receive the active study drug they receive in the Core Part. There is a post-treatment follow-up part for at least 6 months for patients that prematurely discontinue study treatment in the Core Part, that do not enter the Extension Part or that prematurely discontinue study treatment in the Extension part.

Los participantes que completen el período de Tratamiento de la Fase Principal (FP) serán invitados a participar en la Fase de Extensión (FE). En la FE abierta, los participantes recibirán el fármaco de estudio activo que recibieron en la FP. Hay una Fase de seguimiento posterior al tratamiento durante al menos 6 meses para los pacientes que discontinúen prematuramente el tratamiento del estudio en la FP, que no entren a la FE o que discontinúen prematuramente el tratamiento del estudio en la FE

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

2021-07-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-01

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

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