An open-label study evaluating ofatumumab treatment effectiveness and PROs in subjects with RMS transitioning from fumarate-based RMS approved therapies or Fingolimod to Ofatumumab.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

4 Aug 2020 → 11 Mar 2025

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG ORG-100003908

External identifiers

EU CT number

2023-507493-41-00

EudraCT number

2019-001341-40

ClinicalTrials.gov

NCT04353492

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Demonstrate the effectiveness of ofatumumab 20 mg s.c. administered every 4 weeks in subjects with relapsing forms of MS who had breakthrough disease on fumarates or fingolimod.

Secondary objectives 1

1. Evaluate the safety of ofatumumab 20 mg s.c. administrated every 4 weeks in subjects with relapsing forms of MS who had breakthrough disease on fumarates or fingolimod

Conditions and MedDRA coding

relapsing multiple sclerosis (RMS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of MS according to the 2017 Revised McDonald criteria
2. Relapsing MS: relapsing forms of MS (RMS) including RMS and secondary progressive MS (SPMS) (Lublin et al 2014)
3. Disability status at screening defined by Expanded Disability Status Scale (EDSS) score of 0 to 4 (inclusive)
4. MS treatment history with a maximum of 3 Disease Modifying Therapies (DMTs), where all fumarates are considered as one DMT
5. Subject transitioning from either any fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF) or diroximel fumarate (DRF), or fingolimod which was administered for a period of at least 6 months, as their last DMT before first study drug administration
6. Breakthrough disease activity while the participant was adequately using fumarates or fingolimod prior to transitioning for a minimum of 6 months as evidenced by one or more clinically reported relapses or one or more signs of Magnetic Resonance Imaging (MRI) activity (e.g. Gd+ enhancement, new or enlarging T2 lesions)
7. Neurologically stable within one month prior to first study drug administration

Exclusion criteria 13

1. Subjects with primary progressive MS (Polman et al 2011) or SPMS without disease activity (Lublin et al 2014)
2. Subjects meeting criteria for neuromyelitis optica (Wingerchuk et al 2015)
3. Disease duration of more than 10 years since diagnosis
4. Pregnant or nursing (lactating) women
5. Women of child-bearing potential unless they are using highly effective forms of contraception during dosing and for at least 6 months after stopping study medication
6. Subjects with active chronic disease of the immune system other than MS or with immunodeficiency syndrome
7. Subjects with active systemic bacterial, fungal or viral infections (such as hepatitis, HIV, COVID-19), or known to have Acquired Immunodeficiency Syndrome (AIDS)
8. Subjects with neurological symptoms consistent with Progressive Multifocal Leukoencephalopathy (PML) or with confirmed PML
9. Subjects at risk of developing or having reactivation of syphilis or tuberculosis (e.g. subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated), as confirmed by medical history or per local practice
10. Subjects with active hepatitis B and C disease, assessed locally
11. Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration
12. Have been treated with medications as specified or within timeframes specified (e.g. corticosteroids, ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, daclizumab, cyclophosphamide, teriflunomide etc.)
13. Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annual relapse rate (ARR, based on confirmed relapses) measured over the 96 weeks

Secondary endpoints 3

1. Proportion of subjects with adverse events, including injection related reactions
2. Proportion of patients with laboratory or vital signs results meeting abnormal criteria
3. The proportion of subjects discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

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 22

Locations

8 EU/EEA countries · 35 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 24 files

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

Application history

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