A NIS Evaluating Injectable Treatments in Patients With Relapsing Multiple Sclerosis

Recruiting

• Conditions: Relapsing Multiple Sclerosis
• Interventions: Other: ofatumumab; Other: glatiramer acetate; Other: interferon β1

• Registration Number: NCT05344469
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is an observational, non-interventional, multicenter, open-label study in patients being treated with any approved injectable Disease-modifying Therapy (DMT) for Relapsing Multiple Sclerosis in Germany. Prospective, primary data will be collected via questionnaires and an electronic case report form (eCRF) over a period of up to approx. two years of treatment. Additionally, medical history of participants will be collected including disease duration, 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 DMT for RMS as routine medical treatment. This decision must have been made prior to enrollment in this study.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-04-19
• Study First Submitted QC: 2022-04-19
• Study First Posted: 2022-04-25
• Study Start: 2022-05-10
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-10
• Last Update Posted: 2024-05-13
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 800

Inclusion Criteria

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

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Exclusion Criteria

1. Patients being treated outside of the approved label
2. > 5 years since first symptom(s) (leading to MS diagnosis) at enrollment
3. 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)
4. 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
5. Poor recovery from the first two relapses prior to enrollment upon discretion of the investigator
6. EDSS Functional System Score "Pyramidal Functions" ≥ 2 at enrollment
7. Simultaneous participation in any investigational trial or simultaneous participation in another Novartis-sponsored non-interventional study with Ofatumumab

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ofatumumab	ofatumumab	Patients treated with ofatumumab
Standard of Care (SoC)	glatiramer acetate	Patients treated with either interferon β1 (IFN-β1) or glatiramer acetate (GA)
Standard of Care (SoC)	interferon β1	Patients treated with either interferon β1 (IFN-β1) or glatiramer acetate (GA)

Primary Outcome Measures

Name	Time	Method
Proportion of patients who continue to receive their first-line treatment	Month 24	Proportion of patients who continue to receive their first-line treatment (ofatumumab or injectable SOC therapies (IFN-β1 or GA))

Secondary Outcome Measures

Name	Time	Method
Proportion of patients who continue to receive their first-line treatment	Month 12	Proportion of patients who continue to receive their first-line treatment (ofatumumab or injectable SOC therapies (IFN-β1 or GA))
Impact of first-line treatment on health economy	Baseline, month 6, month 12, month 18 and month 24	Mean annual health care resource utilization cost, annual direct medical costs, annual direct nonmedical costs and annual indirect costs as measured by MS Health Resource Utilization Survey \[MS-HRS\]; MS-HRS is a 24-item questionnaire covers societal resource use, regardless of the issue of reimbursement, as well as impact of the disease on work, family and leisure. With the help of this questionnaire a monetary value can be assigned to e.g. the stage of MS, a relapse or a therapy.
Time to onset of confirmed disability progression (CDP)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	Time to onset of confirmed disability progression (CDP) defined as an increase from baseline in EDSS sustained for at least 3 and 6 months, respectively
T1 Gd-enhancing lesions per brain	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	T1 Gd-enhancing lesions per brain to be measured
Fatigue Symptoms and Impact Questionnaire-RMS	Baseline, month 3, month 6, month 12, month 18, month 24	Fatigue Symptoms and Impact Questionnaire-RMS \[FSIQ-RMS\]; The FSIQ-RMS comprises 20 items organized in a conceptual framework with 2 symptom domains (energy, muscle weakness) and 7 impact domains (daily activities, cognition, emotions, physical impact, self-care, sleep, social impact) in order to measure fatigue symptoms and impacts in relapsing multiple sclerosis.; A scoring algorithm standardizes scores on both the symptoms domain (daily and weekly) and impacts subdomains (weekly) to a 0 to 100 scale, with higher scores indicating more severe symptoms and impacts. There is no single summary score across the FSIQ-RMS instrument, but rather 1 symptoms score and 3 impacts subdomain scores.
Generalized Anxiety Disorder Scale 7 [GAD-7]	Baseline, month 3, month 6, month 12, month 18, month 24	The GAD-7 is a validated 7-item anxiety scale to diagnose generalized anxiety disorder. Each of the items is scored 0 to 3, providing a 0 to 21 severity score. Scores of 5, 10, and 15 represent cutpoints for mild, moderate, and severe anxiety, respectively
Expanded disability status scale (EDSS)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	EDSS is a widely used and accepted instrument to evaluate disability status at a given time and, longitudinally, to assess accumulation of disability in clinical studies in MS. The EDSS scale consists of scores in each of seven functional systems (FSs) and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral functions (Fatigue contributes)
Time to onset of confirmed disability improvement (CDI)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	Time to onset of confirmed disability improvement (CDI) defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months
Annualized T2 lesion rate	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	New or enlarging T2 lesions per brain and per year (annualized T2 lesion rate)
Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator.	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator. NEDA3 is defined as no 3mCDP, no confirmed MS relapse and no new or enlarging T2 lesions on any MRI scan compared to baseline
Proportion of patients with no clinical disease activity and no discontinuation of current treatment due to AEs	Up to 24 months	Proportion of patients with no clinical disease activity measured by relapse and disease progression and no discontinuation of current treatment due to AEs (excluding pregnancies) and lack of effectiveness
Number of patients with treatment interruptions	Up to 24 months	Number of patients with treatment interruptions to be collected
Persistence of drug-related adverse events (AEs)	Up to 24 months	Persistence of drug-related adverse events (AEs) including those of special interest (main focus on injection site reactions such as scarring, skin reactions, influenza-like symptoms)
Patient Health Questionnaire 8 [PHQ-8]	Baseline, month 3, month 6, month 12, month 18, month 24	The PHQ-8 is a valid diagnostic and severity measure for depressive disorders. It consists of eight items, each of which is scored 0 to 3, providing a 0 to 24 severity score. Scores of 5, 10, 15, and 20 represent cutpoints for mild, moderate, moderately severe and severe depression, respectively.
Proportion of patients with CDI	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	Proportion of patients with CDI defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months
Proportion of patients who continue to receive their subsequent treatment	Up to 24 months	Proportion of patients who, at a given time over the period of 2 years, continue to receive their subsequent treatment
MS Treatment Concerns Questionnaire [MSTCQ]	Baseline, month 3, month 6, month 12, month 18, month 24	MS Treatment Concerns Questionnaire \[MSTCQ\] is used to assess participants' satisfaction with their treatment injections.; The MSTCQ includes 20 items pertaining satisfaction with the injection system (including issues related to use of the device and preparation of the medication for injection), and AEs related to the patient MS treatment.; All questions have a 5-point response choice, with the responses scored between 1-5. The MSTCQ scores are formed as the sum of all scores. The maximum total score is 100. Lower scores indicate a better state.
Proportion of patients with confirmed disability progression (CDP)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24	Proportion of patients with confirmed disability progression (CDP) defined as an increase from baseline in EDSS sustained for at least 3 and 6 months, respectively
Annualized relapse rate	Up to 24 months	Annualized relapse rate, defined as the number of confirmed Multiple Sclerosis relapses in a year.; Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (\< 37.5°C) or a known infection.
Time to first relapse	Up to 24 months	Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (\< 37.5°C) or a known infection.
Proportion of relapse free patients	Up to 24 months	Relapse defined as an appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and occurred in the absence of fever (\< 37.5°C) or a known infection.
Number of patients and reasons for discontinuation of treatment	Up to 24 months	Number of patients and reasons for discontinuation of treatment classified by category: * efficacy (e.g. occurrence of relapse, evidence of disease activity in MRI); * safety and tolerability (e.g. injection-site reactions, influenza-like symptoms); * or convenience (e.g. inconvenient administration, frequency of injections)
Duration of treatment interruptions per patient	Up to 24 months	Duration of treatment interruptions per patient to be collected
Proportion of drug-related adverse events (AEs)	Up to 24 months	Proportion of drug-related adverse events (AEs) including those of special interest (main focus on injection site reactions such as scarring, skin reactions)
Specific safety assessment of injection related AEs	Up to 24 months	Specific safety assessment of injection related AEs. (i.e. injection site reaction AEs vs. injection systemic reaction AEs) summarized by providing the number and percentage of patients with each of the symptoms and pre-specified grouping of symptoms as well as overall.
Presence of spinal cord lesions	Baseline, month 3,month 6, month 9, month 12, month 15, month 18, month 21, month24	Proportion of patients with spinal cord lesions present
Reasons for and number of treatment interruptions per patient	Up to 24 months	Reasons for and number of treatment interruptions per patient to be collected
Proportion of participants discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons	Up to 24 months	Proportion of participants discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Wolfratshausen, Germany