Clinical trial • Phase III • Neurology

SIPONIMOD FUMARIC ACID for Multiple sclerosis

Phase III trial of SIPONIMOD FUMARIC ACID for Multiple sclerosis.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Multiple sclerosis
Trial Stage
Phase III
Drug Modality
Small molecule|Monoclonal antibody
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
30-05-2024
First CTIS Authorization Date
09-07-2024

Trial design

Randomised, open-label, fingolimod hydrochloride 0.5 mg oral (comparator arm; max daily dose 0.5 mg as listed)-controlled Phase III trial in Romania, Austria, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Fingolimod hydrochloride 0.5 mg oral (comparator arm; max daily dose 0.5 mg as listed)
Target Sample Size
77
Trial Duration For Participant
730

Eligibility

Recruits 77 paediatric patients.

Pregnancy Exclusion
Pregnant or nursing (breastfeeding) female participant
Vulnerable Population
Pediatric population (participants aged 10 to <18 years). Signed informed consent/assent must be obtained prior to participation. Parent/legal guardian consent forms and child/adolescent assent forms are used (separate forms for parent/legal guardian, child assent and adolescent assent are documented). Multiple country-specific ICF and assent documents are available in local languages per country-specific submissions.

Inclusion criteria

  • {"criterion_text":"- Signed informed consent/assent must be obtained prior to participation in the study\n- Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization\n- A diagnosis of MS as defined by the consensus definition for pediatric MS\n- Expanded Disability Status Scale (EDSS) score of 0 to 5.5 (inclusive) at Screening\n- 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"}

Exclusion criteria

  • {"criterion_text":"- Participants with progressive MS\n- Participants meeting the definition of ADEM •\tparticipants meeting criteria for neuromyelitis optica or tested positive for aquaporin 4 (AQP4) at Screening •\tparticipants tested positive for anti-MOG at Screening confirmed centrally\n- Participants with widespread and symmetric white matter alterations in the Screening MRI suggestive of other demyelinating disorders (e.g. metabolic disorders, mitochondrial disorders)\n- Homozygosity for CYP2C9*3, or refusal to test for CYP2C9\n- 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 immune deficiency, drug-induced immune deficiency) or tested positive for HIV at Screening\n- Participants with neurological symptoms consistent with progressive multifocal leukoencephalopathy PML or confirmed PML\n- Participants diagnosed with macular edema during the Screening period\n- Participants with any other significant condition, as assessed by the investigator, which may preclude participant from participating in the study\n- Pregnant or nursing (breastfeeding) female participant\n- Participants with severe active systemic bacterial, viral or fungal infections, including tuberculosis. Treatment initiation should be delayed in participants with an active infection until the infection is resolved\n- Participants with any severe cardiac disease or significant findings during screening, or on the screening ECG\n- Positive results of screening period testing for serological markers for hepatitis A, B, C and E indicating acute or chronic infection\n- Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function\n- Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration\n- Participants without acceptable evidence of immunity to varicella-zoster virus, mumps, measles, rubella, diphtheria, tetanus and pertussis at Randomization\n- Any history of malignancy of any organ system\n- Participants treated with any of the listed medication as Exclusion Medication within defined timespan"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Annualized relapse rate (ARR of confirmed relapses)","definition_or_measurement_approach":"Assessed by annualized relapse rate (ARR) of confirmed relapses"}

Secondary endpoints

  • {"endpoint_text":"- Annualized relapse rate (ARR of confirmed relapses)","definition_or_measurement_approach":"Assessed by annualized relapse rate (ARR) of confirmed relapses"}
  • {"endpoint_text":"- Number of new or newly enlarging T2 lesions on MRI per year (annualized T2 lesion rate)","definition_or_measurement_approach":"Count of new or newly enlarging T2 lesions on MRI per year (annualized T2 lesion rate)"}
  • {"endpoint_text":"- Neurofilament light chain (NfL) concentration in serum","definition_or_measurement_approach":"Measurement of serum neurofilament light chain (NfL) concentration"}
  • {"endpoint_text":"- Ofatumumab and siponimod and (metabolite M17) plasma concentrations","definition_or_measurement_approach":"Plasma concentration measurements of ofatumumab, siponimod and metabolite M17"}
  • {"endpoint_text":"- Proportion of participants with anti-ofatumumab antibodies","definition_or_measurement_approach":"Assessment of presence of anti-ofatumumab antibodies in participants"}
  • {"endpoint_text":"- Adverse events, Columbia Suicide Severity Rating Scale (C-SSRS), ECG, laboratory and ophthalmological data, pulmonary function tests and vital signs","definition_or_measurement_approach":"Safety assessments including adverse event reporting, C-SSRS, ECGs, laboratory tests, ophthalmological evaluations, pulmonary function tests and vital signs"}

Recruitment

Planned Sample Size
77
Recruitment Window Months
121
Consent Approach
Signed informed consent and assent required prior to participation. Parent/legal guardian consent forms and child/adolescent assent forms are specified (separate Parent Legal Guardian, Child Assent, Adolescent Assent documents). Country-specific ICF/assent documents are provided in local languages as part of the submissions.

Geography

Total Number Of Sites
26
Total Number Of Participants
64

Romania

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
11-07-2024
Processing Time Days
20
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
Department Name
3021: Pediatric Neurology
Contact Person Name
Dana Cristina Craiu
Contact Person Email
dcraiu@yahoo.com

Austria

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
15-07-2024
Processing Time Days
24
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Medical University Of Vienna
Department Name
1011 : Deaprtment Neurology
Contact Person Name
Barbara Kornek

Italy

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
15-07-2024
Processing Time Days
24
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
2413: Dip. di Neuroscienze, Scienze riproduttive ed odontostomatologiche- Centro Sclerosi multipla
Contact Person Name
Vincenzo Brescia Morra
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
2412: U.O Neurologia
Contact Person Name
Laura Papetti
Contact Person Email
laura.papetti@opbg.net

Slovakia

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
18
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Narodny Ustav Detskych Chorob
Department Name
3300: Klinika detskej neurológie LFUK a NÚDCH
Contact Person Name
Miriam Kolníková
Contact Person Email
Miriam.Kolnikova@nudch.eu

Poland

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
18-07-2024
Processing Time Days
27
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
2812: Klinika Neurologii Rozwojowej i Epileptologii
Contact Person Name
Katarzyna Połatyńska
Contact Person Email
k.polatynska@gmail.com
Site Name
Instytut Pomnik Centrum Zdrowia Dziecka
Department Name
2813: Klinika Neurologii i Epiletoptologii
Contact Person Name
Katarzyna Kotulska-Jóźwiak
Contact Person Email
k.kotulska@ipczd.pl
Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
2810: Oddział Kliniczny Neurologii Dzieci i Młodzieży
Contact Person Name
Barbara Steinborn
Contact Person Email
bstein@ump.edu.pl
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
2811: Klinika Neurologii Rozwojowej
Contact Person Name
Maria Mazurkiewicz-Bełdzińska
Contact Person Email
mmazur@gumed.edu.pl

Belgium

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
18
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Centre hospitalier universitaire de Liege
Department Name
1141 : Neurology
Contact Person Name
Dominique Dive
Contact Person Email
Dominique.dive@chu.ulg.ac.be
Site Name
Universitair Ziekenhuis Gent
Department Name
1140 : Pediatry
Contact Person Name
Hélène Verhelst
Contact Person Email
helene.verhelst@ugent.be

Latvia

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
18
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Bernu Kliniska Universitates Slimnica VSIA
Department Name
2510: Neurology Department
Contact Person Name
Dace Pretkalnina
Contact Person Email
dace.pretkalnina@bkus.lv

Portugal

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
10-07-2024
Processing Time Days
19
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Unidade Local De Saude De Coimbra E.P.E.
Department Name
2910: Centro de Desenvolvimento da Criança
Contact Person Name
Filipe Palavra
Contact Person Email
uicc@ulscoimbra.min-saude.pt
Site Name
Unidade Local De Saude De Sao Jose E.P.E.
Department Name
2911: Neurologia
Contact Person Name
Rita Silva
Contact Person Email
rita.silva@chlc.min-saude.pt

France

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
11-07-2024
Processing Time Days
20
Number Of Sites
3
Number Of Participants
13

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
1840: Neurologie Pédiatrie
Contact Person Name
Kumaran Deiva
Contact Person Email
kumaran.deiva@aphp.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
1841: Neurologie
Contact Person Name
Jerome De Seze
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
1842: Neuropediatrie
Contact Person Name
Pierre Meyer
Contact Person Email
p-meyer@chu-montpellier.fr

Germany

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
12-07-2024
Processing Time Days
21
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
Medical Center - University Of Freiburg
Department Name
1925 : Neuropädiatrie und Muskelerkrankungen
Contact Person Name
Matthias Eckenweiler
Site Name
Katholisches Klinikum Bochum gGmbH
Department Name
1921: Kinder und Jugendmedizin
Contact Person Name
Thomas Luecke
Site Name
Universitaetsmedizin Goettingen
Department Name
1920: Kinder und Jugendmedizin/Neuropädiatrie
Contact Person Name
Jutta Gaertner

Spain

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
10-07-2024
Processing Time Days
19
Number Of Sites
4
Number Of Participants
2

Sites

Site Name
Hospital Universitario Ramon Y Cajal
Department Name
3404: Neurología
Contact Person Name
Lucienne Costa Frossard Franca
Contact Person Email
lufrossard@yahoo.es
Site Name
Hospital Universitario Central De Asturias
Department Name
3403: Neurología pediátrica
Contact Person Name
Ignacio Malaga Dieguez
Site Name
Hospital Universitario De Cruces
Department Name
3401: Neurología
Contact Person Name
Maria del Mar Mendibe Bilbao
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
3402: Neurología
Contact Person Name
Sara Eichau Madueno
Contact Person Email
saraeichau@gmail.com

Croatia

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
18
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Children's Hospital Zagreb
Department Name
1540: Pediatry (pediatric neurology)
Contact Person Name
Jadranka Sekelj Fures
Contact Person Email
jadrankasekelj@gmail.com

Estonia

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
15-07-2024
Processing Time Days
24
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Clinic4U OÜ
Department Name
1721: Neurology
Contact Person Name
Katrin Gross-Paju

Sponsor

Primary sponsor

Full Name
Novartis Pharma AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Parexel International (IRL) Limited
Responsibilities
code:12
Name
IQVIA Limited
Responsibilities
Management of drug supply logistics, dispensing and unblinding
Name
Icon Laboratory Services Inc.
Responsibilities
Genotyping sample analysis
Name
Syneos Health Inc.
Responsibilities
code:1
Name
Medidata Solutions Inc.
Responsibilities
EDC system provider & data storage
Name
Labcorp Central Laboratory Services LP
Responsibilities
code:4
Name
Eresearchtechnology Inc.
Responsibilities
Data collection via tablet and hand-held device / Central ECG reading
Name
Q Squared Solutions Limited
Responsibilities
Central laboratory, clinical chemistry

Third parties

  • {"country":"Switzerland","full_name":"Universitaetsspital Basel","duties_or_roles":"EDSS expert consultancy, Neurostatus EDSS rater certification","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code:12","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Management of drug supply logistics, dispensing and unblinding","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Genotyping sample analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive Activation sites activities","organisation_type":"Pharmaceutical company"}
  • {"country":"Latvia","full_name":"Oribalt Riga SIA","duties_or_roles":"Collection and destruction of the investigational medicinal products","organisation_type":"Pharmaceutical company"}
  • {"country":"Poland","full_name":"Eco-Abc Sp. z o. o.","duties_or_roles":"Destruction of the investigational medicinal products","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central laboratory, clinical chemistry","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient reimbursement","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Croatia","full_name":"Medical Intertrade d.o.o.","duties_or_roles":"Obtain license, import study drugs and medical equip, storage&Logistics, support supplies, return&destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Patients","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Romania","full_name":"Alliance Healthcare Romania S.R.L.","duties_or_roles":"Supply and delivery of Non-IMP Destruction of IMP and non-IMP","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"Medical image analysis, central reading","organisation_type":"Pharmaceutical company"}
  • {"country":"Austria","full_name":"Abf Pharmaceutical Services GmbH","duties_or_roles":"Local depot for storage, distribution of AxMP to sites/ final Rec. + Destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Packaging of study drug","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"Analysis of neutralizing antibodies (NAb)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Medical equipment supplier, management and maintenance","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Phardis S.r.l.","duties_or_roles":"Local equipment storage","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Data collection via tablet and hand-held device","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"EDC system provider & data storage","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"DATAMAP-Gesellschaft fuer Datenmanagement Datenanalyse und Datenpraesentation mbH","duties_or_roles":"Programming supporting DMC","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Latvia","full_name":"Oribalt Riga SIA","duties_or_roles":"IMP destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG reading","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"SGS France","duties_or_roles":"Pharmacokinetics (PK) analyses for: BAF312 and FTY720","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
  • {"country":"Slovakia","full_name":"Movianto Slovensko s.r.o.","duties_or_roles":"Destruction and storage of returned study medication","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BAF312
Active Substance
SIPONIMOD FUMARIC ACID
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus:1
Frequency
daily
Maximum Dose
2 mg
Investigational Product Name
OFATUMUMAB
Active Substance
OFATUMUMAB
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS USE
Route
SUBCUTANEOUS
Authorisation Status
prodAuthStatus:2
Maximum Dose
20 mg
Investigational Product Name
FINGOLIMOD HYDROCHLORIDE
Active Substance
FINGOLIMOD HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus:2
Frequency
daily
Maximum Dose
0.5 mg
Investigational Product Name
Placebo to Ofatumumab (OMB157) [Kesimpta]
Modality
Other
Investigational Product Name
Placebo to Siponimod (BAF312) [Mayzent] film-coated tablets
Modality
Other
Investigational Product Name
Placebo to Fingolimod (FTY720) [Gilenya] 0.25mg & 0.5mg
Modality
Other

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