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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Oct 2021 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG, OMS ID: ORG-100003908

External identifiers

EU CT number

2024-511686-11-00

EudraCT number

2020-002700-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Therapy, Pharmacodynamic, Safety, Pharmacokinetic

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

Secondary objectives 6

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

Conditions and MedDRA coding

Multiple Sclerosis in pediatric patients

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002397-PIP01-18, EMEA-000716-PIP01-09

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinica/studydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Signed informed consent/assent must be obtained prior to participation in the study
2. Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
3. A diagnosis of MS as defined by the consensus definition for pediatric MS
4. Expanded Disability Status Scale (EDSS) score of 0 to 5.5 (inclusive) at Screening
5. 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 17

1. Participants with progressive MS
2. 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
3. Participants with any severe cardiac disease or significant findings during screening, or on the screening ECG
4. Positive results of screening period testing for serological markers for hepatitis A, B, C and E indicating acute or chronic infection
5. Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function
6. Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration
7. Participants without acceptable evidence of immunity to varicella-zoster virus, mumps, measles, rubella, diphtheria, tetanus and pertussis at Randomization
8. Any history of malignancy of any organ system
9. Participants treated with any of the listed medication as Exclusion Medication within defined timespan
10. 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 confirmed centrally
11. Participants with widespread and symmetric white matter alterations in the Screening MRI suggestive of other demyelinating disorders (e.g. metabolic disorders, mitochondrial disorders)
12. Homozygosity for CYP2C9*3, or refusal to test for CYP2C9
13. 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
14. Participants with neurological symptoms consistent with progressive multifocal leukoencephalopathy PML or confirmed PML
15. Participants diagnosed with macular edema during the Screening period
16. Participants with any other significant condition, as assessed by the investigator, which may preclude participant from participating in the study
17. Pregnant or nursing (breastfeeding) female participant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized relapse rate (ARR of confirmed relapses)

Secondary endpoints 6

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Comparator 2

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 28

Locations

13 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 265 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications