A Study of End of Dose Phenomena in Subcutaneous Natalizumab Treated Multiple Sclerosis (MS) Participants (SATURATE-MS)

End of Dose Phenomena in Subcutaneous Natalizumab Treated MS Patients

The primary objective of this study is to better understand the pathophysiological background of end-of-dose symptoms (EOD) and thereby determine the percentage of participants who develop EOD under natalizumab (NTZ) as an example of interval therapy in MS and to detect specific changes through multimodal analyses, including radiological, blood and digital health measurements, that may be used as potential biomarkers in the future to map EOD.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab

Detailed Description

Participants will additionally be offered to record daily activity and sleep patterns as well as heart rate for the duration of the study.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • Klinik für Neurologie, Universitätsklinikum Düsseldorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include MS participants under NTZ therapy.

Description

Key Inclusion Criteria:

• Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS) according to 2017 revised McDonald criteria
• Initiation of treatment with SC NTZ according to summary of product characteristic (SmPC) and in accordance to national guidelines or
• Continuing treatment with IV NTZ
• Owns and be able to handle a smartphone

Key Exclusion Criteria:

• Participants with an acute MS relapse and/or a history of intravenous corticosteroid treatment within past six weeks
• Any comorbidity resulting in an impairment to understand or successfully complete the study such as (but not restricted to) psychiatric comorbidities or dementia
• Diagnosis of primary or secondary progressive MS
• Additional immunosuppression except of natalizumab

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Natalizumab (NTZ); Participants who receive NTZ intravenously (IV) or subcutaneously (SC) as standard interval dosing (SID), or as SC extended interval dosing (EID) will be followed prospectively for up to 30 weeks.	Drug: Natalizumab; Administered as specified in the treatment arm.; Other Names: Tysabri

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants who Develop End of Dose Symptoms (EOD) Under NTZ	Up to 30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Expanded Disability Status Scale (EDSS) Score	The EDSS is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Higher scores indicate the worse level of disability.	Baseline up to 30 weeks
Change From Baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC)	Fatigue is rated using the self-administered 20-item FSMC questionnaire that includes ten questions related to motor fatigue and ten questions related to cognitive fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Minimum value is 20 (no fatigue at all) and maximum value is 100 (severe fatigue). Higher scores indicate higher fatigue.	Baseline up to 30 weeks
Change From Baseline in Fatigue Severity Scale (FSS)	The FSS is a self-assessment questionnaire that provides a score as a measurement of the severity of fatigue. It consists of 9 questions scored from 1 to 7, low value indicates strong disagreement with the statement, whereas a high value indicates strong agreement. A total score of 36 or more suggests the presence of fatigue.	Baseline up to 30 weeks
Change From Baseline in World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Score	The WHOQOL-BREF questionnaire measures quality of life across 4 domains: Physical health, psychological health, social relationships and environment. It also includes one question on overall QOL and one on general health. The WHOQOL-BREF scores correlate highly (.89 or above) with WHOQOL-100 scores, and demonstrate good discriminant validity, content validity, internal consistency and test-retest reliability. The four WHOQOL-BREF domain scores will be used as main outcome measure. The measure is calculated by summing the point values for the questions corresponding to each domain and then transforming the scores to a 0-100 point interval, higher score correspond to greater QOL.	Baseline up to 30 weeks
Change From Baseline in Brief Fatigue Inventory (BFI) Score	A questionnaire will be used to measure the severity of fatigue in the past 24 hours. This 9-item self-reported questionnaire is scored on a 0-10 numerical rating scale, where 0 and 10 represent absence and the highest severity of fatigue, respectively.	Baseline up to 30 weeks
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score	MSFC has 2 components: Timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) [dominant and nondominant hands]. The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score. MSFC Z-score = (Z25-foot-walk + Z9HPT-2)/2, where Zj refers to Z-scores of component j. A Z-score represented the number of standard deviations participant's test result was higher (Z >0) or lower (Z <0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.	Baseline up to 30 weeks

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: DE-TYS-12185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No