A NIS Evaluating Various Injectable and Oral Treatments in Patients With Relapsing Multiple Sclerosis

Official title

A Non-interventional Study Evaluating Injectable Treatments (Ofatumumab, Glatiramer Acetate and Interferon β1) and Oral Treatments (Teriflunomide, Dimethyl Fumarate and Diroximel Fumarate) in Patients With Relapsing Multiple Sclerosis [AIOLOS]

Overview

This is an observational, non-interventional, multicenter, open-label study in patients being treated with any approved injectable or selected oral DMT for RMS in Germany. Prospective, primary data will be collected via questionnaires and an electronic case report form (eCRF) over a period of up to four years. Additionally, medical history of participants will be collected including disease duration, laboratory values, EDSS, MRI parameters and relapses.

Detailed description

The prerequisite for participation in this observational study is the independent decision of the treating physician and patient to start an approved injectable or oral DMT for RMS as routine medical treatment. This decision must have been made prior to enrollment in this study.

Cohort 1: The prospective observational period per patient in the core part will be up to approx. two years from the time of consent (2 years +2 months visit window). If a patient re-consents to the extension part, then the prospective extension observational period will be additional approx. two years, resulting in a total observational period (prospectively for the core and extension part \& retrospectively for the potential gap between core and extension part) of approx. 4 years (+ 2 month visit window).

Cohort 2: The prospective observational period per patient will be up to approx. two years from the time of consent (2 years + 2 months visit window).

The observational period will not be dictated by the protocol. The follow-up documentation will take place at a frequency defined as per investigator's discretion. The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy and to routine clinical care, can be performed as telemedicine visits and will take place as per investigator's discretion.

Interventions

• Other ofatumumab
  There is no treatment allocation. Patients administered ofatumumab by prescription that have started as routine medical treatment will be enrolled.
• Other glatiramer acetate
  There is no treatment allocation. Patients administered glatiramer acetate by prescription that have started as routine medical treatment will be enrolled.
• Other interferon β1
  There is no treatment allocation. Patients administered interferon β1 by prescription that have started as routine medical treatment will be enrolled.
• Other teriflunomide
  There is no treatment allocation. Patients administered teriflunomide by prescription that have started as routine medical treatment will be enrolled.
• Other dimethyl fumarate (DMF)
  There is no treatment allocation. Patients administered dimethyl fumarate (DMF) by prescription that have started as routine medical treatment will be enrolled.
• Other diroximel fumarate (DRF)
  There is no treatment allocation. Patients administered diroximel fumarate (DRF) by prescription that have started as routine medical treatment will be enrolled.

Primary outcome measures

• Proportion of patients who continue to receive their baseline treatment [Time frame: Month 24]

Secondary outcome measures (12)

• Proportion of patients who continue to receive their baseline treatment [Time frame: Month 12]
• Time to event analysis for retention time on baseline treatment [Time frame: From Baseline to event, up to 24 months]
• Impact of first-line treatment on health economy [Time frame: Baseline, month 6, month 12, month 18 and month 24]
• Fatigue Symptoms and Impact Questionnaire-RMS [Time frame: Baseline, month 3, month 6, month 12, month 18, month 24]
• Patient Health Questionnaire 8 [PHQ-8] [Time frame: Baseline, month 3, month 6, month 12, month 18, month 24]
• Generalized Anxiety Disorder Scale 7 [GAD-7] [Time frame: Baseline, month 3, month 6, month 12, month 18, month 24]
• Multiple Sclerosis Impact Scale 29 v2 [Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24]
• Quality of Life in Neurological Disorders [NeuroQoL] [Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21 and month 24]
• MS Treatment Concerns Questionnaire [MSTCQ] [Time frame: Baseline, month 3, month 6, month 12, month 18, month 24]
• Expanded disability status scale (EDSS) [Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24]
• Time to onset of confirmed disability worsening (CDW) [Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24]
• Proportion of patients with confirmed disability worsening (CDW) [Time frame: Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24]

Eligibility criteria

Cohort 1 Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male or female patients aged ≥18 years at enrollment
• Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018b)
• RMS with active disease as defined by Lublin et al. (2014)
• Max. 1 relapse during the previous year and max. 2 relapses during the previous two years prior to enrollment
• Disability status at enrollment with an EDSS score of 0 to 2.5 (inclusive)
• Planned initiation or initiation within the past 14 days with an approved injectable DMT for MS as routine medical treatment

Cohort 2 Inclusion Criteria:

• Signed informed consent must be obtained prior to participation,
• Male or female patients aged ≥18 years at enrollment,
• Diagnosis of MS according to the 2024 revised McDonald criteria (Montalban et al., 2025),
• RMS with active disease as defined by Lublin et al. (2014) ,
• Max. 1 relapse during the previous year and max. 2 relapses during the previous two years prior to enrollment,
• Disability status at enrollment with an EDSS score of 0 to 3.0 (inclusive),
• Planned initiation or initiation within the past 14 days with an approved injectable or oral DMT for MS as routine medical treatment:

• Ofatumumab: only naïve patients or patients previously treated with max. one DMT other than ofatumumab
• IFN-β1, GA, teriflunomide, DMF or DRF: only naïve patients

Cohort 1 Exclusion Criteria:

• Patients being treated outside of the approved label
• > 5 years since first symptom(s) (leading to MS diagnosis) at enrollment
• Previous therapy with any DMT for the treatment of MS prior to enrollment (except within the past 14 days with an approved injectable DMT for MS as routine medical treatment; see Inclusion criteria #7)
• Relapse prior to enrollment which has led to a severe deficit relevant to everyday life upon discretion of the investigator after exhaustion of the relapse therapy
• Poor recovery from the first two relapses prior to enrollment upon discretion of the investigator
• EDSS Functional System Score "Pyramidal Functions" ≥ 2 at enrollment
• Simultaneous participation in any investigational trial or simultaneous participation in another Novartis-sponsored non-interventional study with Ofatumumab

Cohort 2 Exclusion Criteria:

• Patients being treated outside of the approved label,
• >5 years since first symptom(s) (leading to MS diagnosis) at enrollment,
• Simultaneous participation in any investigational trial or simultaneous participation in another Novartis-sponsored non-interventional study with Ofatumumab,
• Patients being previously enrolled in cohort 1 are not eligible to be enrolled into cohort 2

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 141 centers

• Novartis Investigative Site — Albstadt
• Novartis Investigative Site — Hettingen
• Novartis Investigative Site — Hettingen
• Novartis Investigative Site — Mannheim
• Novartis Investigative Site — Nagold
• Novartis Investigative Site — Schwäbisch Hall
• Novartis Investigative Site — Schwetzingen
• Novartis Investigative Site — Bamberg
• … and 133 more centers

Identifiers

NCT: NCT05344469 · COMB157GDE02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗