An open-label, single arm, multi-center extension study evaluating long-term safety, tolerability and effectiveness of ofatumumab in subjects with relapsing multiple sclerosis

MS is a long-term illness where the body*s immune system attacks and damages
the protective covering (called myelin) around the nerves in the central
nervous system. Damaged myelin results in scar tissue or *sclerosis*. Because
this scar tissue does not transfer signals from the
brain as well as normal myelin, nerves stop working properly. Such scars can be
seen on a scan called magnetic resonance imaging (MRI).
People with relapsing MS will have repeated attacks, or *relapses*. During
these relapses, the own immune system attacks the nerves in the brain or spinal
cord, damaging the myelin covering. This can result in symptoms including
difficulty walking, balance problems, vision
problems, and more. Some symptoms may not completely recover after the relapse
leading to accumulation of disability over time.
The immune system is made up of many different types of cells that work
together to fight infection, among them B-cells and lymphocytes, which are
types of white blood cells. Ofatumumab targets cells in the immune system by
temporarily removing the number of Bcells, a type of white blood cell. White
blood cells are involved in the process of inflammation that is believed to
play a role in damaging the myelin and in some of the symptoms in MS. Bcells
produce *antibodies* which fight infection but are also responsible for some of
the damage that is done to the nerve cells in MS.
In the Netherlands, ofatumumab is approved and *on the market* for the
treatment of Chronic Lymphocytic Leukemia (CLL), a cancer of the blood which
affects a type of white blood cell called lymphocytes. However, for use in CLL,
the dose is much higher than will be used in this
study. In CLL, the medication is administered into a vein but for this MS
research study, the medication will be given by an injection under the skin
(subcutaneous injection).
Ofatumumab has not yet been approved for the treatment of people with relapsing
MS. Therefore, ofatumumab is currently not *on the market* for MS in any
country.
Around 267 patients with relapsing-remitting MS have been treated with
ofatumumab (most via injection under the skin) in completed clinical studies to
date (details on these studies can be found in Section 5). In addition, there
are two large trials ongoing with more than 1800
patients with relapsing MS participating (with half the patients receiving
ofatumumab treatment). This study will enroll patients that have participated
in other ofatumumab studies and provide the opportunity for Novartis to study
ofatumumab long-term safety and efficacy.
This study does not compare ofatumumab to any other treatment for MS; all
patients will be treated with ofatumumab.

COVID-19 substudy:
People taking ofatumumab have a reduced number of B-cells available to produce
antibodies following vaccination which may reduce the effectiveness of
vaccination. It is important to determine if people treated with ofatumumab are
able to develop a protective immune response after vaccination against
COVID-19.

This study has been transitioned to CTIS with ID 2023-507906-15-00 check the CTIS register for the current data.

This study is designed to collect long-term safety, tolerability, effectiveness
and health outcomes data in RMS patients.

COVID-19 substudy:
The purpose of this COVID-19 research sub-study is to determine the effects of
the study treatment (ofatumumab) on the development of an immune response to
selected SARS-CoV-2 (COVID-19) vaccines in participants with RMS.

This study uses an open-label, multi-center, single treatment arm design,
enrolling subjects that have participated in a Novartis ofatumumab MS clinical
study. This study has 3 main Parts:
* Part 1 - Screening
* Part 2 - Loading
* Part 3 - Open-Label Treatment

COVID-19 substudy:
During a number of visits of the main study, additional blood samples may be
taken for a number of patients. Depending on
which visit the participant is on a C-SSRS will be completed. Participation is
voluntary.
The substudy will run for a maximum of 12 months (or until the end of the main
study if this is sooner).

1. Ofatumumab (OMB157G) 20 mg sc injection on Day 1, Day 7, Day 14 and every 4
weeks (q4) from month 1.
2. Placebo sc on Day 1 and Day 14 if applicable.

COVID-19 substudy:
no intervention

Risks: Adverse events of the study medication (ofatumumab) and possibly
methylprednisone (premedication), side effects of the tests (blood collection,
injections, accelerated washout of teriflunomide).

Burden:
Visits: Screening, Day 1, day 7 and 14, Week 4 (W4), followed by every 12 weeks
in the first 2 years, then every 24 weeks until the 5th year of the study,
thereafter yearly until 8th year.
Physical examination at screening, thereafter at each visit, end of study
visit(s)
Vital Signs: at screening, Day 1 and from W4 onwards at each visit in the first
year, then every 24 weeks until 5th year, thereafter yearly until 8th year, end
of study visit(s)
Blood tests: at screening, Day 1 and from W4 onwards at each visit in the first
year, then every 24 weeks until 5th yr, thereafter yearly until 8th yr, end
visit(s), M3, 6, 9 in follow-up period.
Pregnancy tests: during screening, then annually and at end of study visit(s)
via blood test, monthly test at home via urine examination.
ECG at screening and at end of study visit of 5th yr.
MRI at screening, annually until 5th yr, end of study visit of 5th yr, M6 in
follow-up period.
Neurological examination (EDSS) at screening, every visit until 8th year, end
of study visit(s), M3,6,9 in follow-up period.
SDMT: screening, day 1, from W12 onwards every visit in the first 2 years, then
every 24 weeks until 5th yr, end of study visit 5th yr.
Questionnaire 'state of mind; : Screening and Day 1, then at each visit until
5th yr, end of study visit 5th yr.
Other questionnaires: screening and day 1, annually until 5th yr, end of study
visit 5th yr.
Monthly telephone call if no visit.


COVID-19 substudy:
Additional blood sampling: first visit after signing Informed Consent, at 3,6,9
and 12 months after first vaccination or booster
Suicidal questionnaire: depending on which visit the participant is on..