A NIS Evaluating Injectable Treatments in Patients With Relapsing Multiple Sclerosis

Relapsing Multiple Sclerosis Clinical Trial

— AIOLOS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05344469
• Other study ID #: COMB157GDE02
• Status: Recruiting
• Start date: May 10, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Other:
• ofatumumab
There is no treatment allocation. Patients administered ofatumumab by prescription that have started as routine medical treatment will be enrolled.
• glatiramer acetate
There is no treatment allocation. Patients administered glatiramer acetate by prescription that have started as routine medical treatment will be enrolled.
• interferon ß1
There is no treatment allocation. Patients administered interferon ß1 by prescription that have started as routine medical treatment will be enrolled.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Altenburg
Germany	Novartis Investigative Site	Altenholz
Germany	Novartis Investigative Site	Altmark	Sachsen-Anhalt
Germany	Novartis Investigative Site	Alzey
Germany	Novartis Investigative Site	Bad Homburg
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Bamberg	Bavaria
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Bergneustadt
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Boblingen
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dessau
Germany	Novartis Investigative Site	Dillingen
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Erbach
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Falkensee	Brandenburg
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Fulda
Germany	Novartis Investigative Site	Gelsenkirchen
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Gladenbach
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Halle (Saale)
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover	Lower Saxony
Germany	Novartis Investigative Site	Hannover	Lower Saxony
Germany	Novartis Investigative Site	Hettingen	Baden Wuerttemberg
Germany	Novartis Investigative Site	Ingelheim
Germany	Novartis Investigative Site	Itzehoe
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kaiserslautern
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luenen
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Meerbusch	North Rhine-Westfalia
Germany	Novartis Investigative Site	Mettmann
Germany	Novartis Investigative Site	Minden
Germany	Novartis Investigative Site	Muelheim an der Ruhr
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Muenster	Northwest
Germany	Novartis Investigative Site	Mühlhausen
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Munich	Bavaria
Germany	Novartis Investigative Site	Nagold
Germany	Novartis Investigative Site	Neuburg an der Donau
Germany	Novartis Investigative Site	Neuruppin
Germany	Novartis Investigative Site	Nuernberg
Germany	Novartis Investigative Site	Oer-Erkenschwick	Northrhine Westfalia
Germany	Novartis Investigative Site	Osnabrück
Germany	Novartis Investigative Site	Pforzheim
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Remscheid
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Ruedersdorf
Germany	Novartis Investigative Site	Ruelzheim
Germany	Novartis Investigative Site	Saalouis
Germany	Novartis Investigative Site	Schwaebisch	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Schwetzingen	BW
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Stadtroda
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Trier
Germany	Novartis Investigative Site	Tuebingen
Germany	Novartis Investigative Site	Unterhaching
Germany	Novartis Investigative Site	Untermeiting	Bayern
Germany	Novartis Investigative Site	Weil der Stadt
Germany	Novartis Investigative Site	Wildeshausen	Lower Saxony
Germany	Novartis Investigative Site	Wolfratshausen

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who continue to receive their first-line treatment	Proportion of patients who continue to receive their first-line treatment (ofatumumab or injectable SOC therapies (IFN-ß1 or GA))	Month 24
Secondary	Proportion of patients who continue to receive their first-line treatment	Proportion of patients who continue to receive their first-line treatment (ofatumumab or injectable SOC therapies (IFN-ß1 or GA))	Month 12
Secondary	Impact of first-line treatment on health economy	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.	Baseline, month 6, month 12, month 18 and month 24
Secondary	Fatigue Symptoms and Impact Questionnaire-RMS	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.	Baseline, month 3, month 6, month 12, month 18, month 24
Secondary	Patient Health Questionnaire 8 [PHQ-8]	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.	Baseline, month 3, month 6, month 12, month 18, month 24
Secondary	Generalized Anxiety Disorder Scale 7 [GAD-7]	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	Baseline, month 3, month 6, month 12, month 18, month 24
Secondary	MS Treatment Concerns Questionnaire [MSTCQ]	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.	Baseline, month 3, month 6, month 12, month 18, month 24
Secondary	Expanded disability status scale (EDSS)	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)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Time to onset of confirmed disability progression (CDP)	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	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Proportion of patients with confirmed disability progression (CDP)	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	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Time to onset of confirmed disability improvement (CDI)	Time to onset of confirmed disability improvement (CDI) defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Proportion of patients with CDI	Proportion of patients with CDI defined as a decrease from baseline in EDSS sustained for at least 3 and 6 months	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	T1 Gd-enhancing lesions per brain	T1 Gd-enhancing lesions per brain to be measured	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Annualized T2 lesion rate	New or enlarging T2 lesions per brain and per year (annualized T2 lesion rate)	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Proportion of patients with no evidence of disease activity (NEDA3) upon discretion of the investigator.	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	Baseline, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24
Secondary	Proportion of patients with no clinical disease activity and no discontinuation of current treatment due to AEs	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	Up to 24 months
Secondary	Annualized relapse rate	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.	Up to 24 months
Secondary	Time to first relapse	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.	Up to 24 months
Secondary	Proportion of relapse free patients	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.	Up to 24 months
Secondary	Number of patients and reasons for discontinuation of treatment	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)	Up to 24 months
Secondary	Proportion of patients who continue to receive their subsequent treatment	Proportion of patients who, at a given time over the period of 2 years, continue to receive their subsequent treatment	Up to 24 months
Secondary	Reasons for and number of treatment interruptions per patient	Reasons for and number of treatment interruptions per patient to be collected	Up to 24 months
Secondary	Duration of treatment interruptions per patient	Duration of treatment interruptions per patient to be collected	Up to 24 months
Secondary	Number of patients with treatment interruptions	Number of patients with treatment interruptions to be collected	Up to 24 months
Secondary	Proportion of drug-related adverse events (AEs)	Proportion of drug-related adverse events (AEs) including those of special interest (main focus on injection site reactions such as scarring, skin reactions)	Up to 24 months
Secondary	Persistence of drug-related adverse events (AEs)	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)	Up to 24 months
Secondary	Specific safety assessment of injection related AEs	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.	Up to 24 months
Secondary	Proportion of participants discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons	Proportion of participants discontinuing treatment due to insufficient effectiveness (lack of efficacy) or tolerability/safety reasons	Up to 24 months
Secondary	Presence of spinal cord lesions	Proportion of patients with spinal cord lesions present	Baseline, month 3,month 6, month 9, month 12, month 15, month 18, month 21, month24