Back to resultsA Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Recruiting
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Natalizumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting
Eligibility Criteria
Key Inclusion Criteria:
- Diagnosis of RRMS according to the McDonald criteria
- Treatment-naïve in respect to natalizumab as disease modifying monotherapy for RRMS
- No or not more than one prior MS disease-modifying therapy
- Highly active RRMS, as defined by at least one relapse in the previous year and at least one T1 gadolinium-enhancing lesion or ≥3 new or enlarging T2 lesions
- EDSS score ≤ 5.5 at Screening
- Estimated glomerular filtration rate (eGFR) >30 millilitre per min (mL/min), as estimated using the Cockcroft-Gault formula.
Key Exclusion Criteria:
- Primary- and secondary-progressive MS
- Participants for whom MRI is contraindicated
- History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study
- History of severe allergic or anaphylactic reactions or known hypersensitivity to any antibody drug therapy.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Neurologische Praxis Dr. med. Boris-Alexander KallmannRecruiting
- Neurologische Studiengesellschaft Bonn GbRRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Natalizumab
Arm Description
Participants will receive natalizumab 300 milligrams (mg) (2*150 mg), SC injection, once every 4 weeks (Q4W) up to Week 24.
Outcomes
Primary Outcome Measures
Cumulative Number of Active Lesions (CUALs) Through Week 24
Cumulative number of active lesions will be calculated as the sum of the number of gadolinium (Gd)-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1-weighted (T1w) scans. It is also referred to as combined unique active lesions (CUALs).
Secondary Outcome Measures
Cumulative Number of CUALs Through Weeks 4, 8, and 12
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Absolute Number of CUALs at Weeks 4, 8, 12, and 24
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Mean Change From Baseline of CUALs at Weeks 4, 8, 12, and 24
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Cumulative Number of New Gd-Enhancing Lesions Through Weeks 4, 8, 12, and 24
Cumulative number will be calculated as the sum of the number of Gd-enhancing lesions through Weeks 4, 8, 12, and 24.
Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Absolute Number of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Change From Baseline of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Cumulative Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Cumulative number will be calculated as the sum of the number of new or enlarging T2 hyperintense lesions through Weeks 4, 8, 12, and 24.
Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Change From Baseline of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Annualized Relapse Rate
Multiple sclerosis (MS) relapse is defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. ARR is defined as the total number of relapses divided by the total participant-time at risk of relapse.
Time to First Relapse
MS relapse is defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. Time to first MS relapse will be calculated as the date from first study drug administration through the date of the first relapse, if applicable.
Number of Participants With Expanded Disability Status Scale (EDSS) Improvement and Stable Disease and Worsening at Weeks 12, and 24
The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Stable disease is defined as +/- 0.5 change of EDSS. Worsening is > 0.5 increase of EDSS.
Trough Serum Natalizumab Concentration (Ctrough)
Trough alpha 4 (α4) Integrin Saturation
Change From Baseline in Lymphocyte Subsets Count
Lymphocyte subsets include T cells, B cells and natural killer cells (cluster of differentiate 4 [CD4], CD8, CD19, and CD56).
Change From Baseline in Anti-Natalizumab Antibodies
Persistence of Anti-Natalizumab Antibodies
Re-test will be done for antibodies after 6 weeks of first positive result.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05532163
Brief Title
A Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
Official Title
A Prospective, Multicenter, Interventional, Open-Label, Single-arm Phase IV Study Over 24 Weeks to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous Natalizumab in Patients With Relapsing-Remitting Multiple Sclerosis (TYS-ON)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 23, 2023 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the radiological efficacy of SC natalizumab over time through Week 24 in natalizumab-naïve participants, as measured by brain magnetic resonance imaging (MRI). The secondary objectives of this study are to evaluate additional lesion-related radiological efficacy measures over time, relapse-based clinical efficacy measures, disability improvement and worsening (EDSS), pharmacokinetic and pharmacodynamic parameters, the immunogenicity of repeated doses, and safety in treatment-naïve participants of SC natalizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Natalizumab
Arm Type
Experimental
Arm Description
Participants will receive natalizumab 300 milligrams (mg) (2*150 mg), SC injection, once every 4 weeks (Q4W) up to Week 24.
Intervention Type
Drug
Intervention Name(s)
Natalizumab
Other Intervention Name(s)
Tysabri, BG00002
Intervention Description
Administered as specified in the treatment arm
Primary Outcome Measure Information:
Title
Cumulative Number of Active Lesions (CUALs) Through Week 24
Description
Cumulative number of active lesions will be calculated as the sum of the number of gadolinium (Gd)-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1-weighted (T1w) scans. It is also referred to as combined unique active lesions (CUALs).
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Cumulative Number of CUALs Through Weeks 4, 8, and 12
Description
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Time Frame
Weeks 4, 8, and 12
Title
Absolute Number of CUALs at Weeks 4, 8, 12, and 24
Description
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Time Frame
Weeks 4, 8, 12, and 24
Title
Mean Change From Baseline of CUALs at Weeks 4, 8, 12, and 24
Description
CUALs will be calculated as the sum of the number of Gd-enhancing lesions and new or enlarging T2 hyperintense lesions that are non-enhancing on post-gadolinium T1w scans.
Time Frame
Baseline, Weeks 4, 8, 12, and 24
Title
Cumulative Number of New Gd-Enhancing Lesions Through Weeks 4, 8, 12, and 24
Description
Cumulative number will be calculated as the sum of the number of Gd-enhancing lesions through Weeks 4, 8, 12, and 24.
Time Frame
Weeks 4, 8, 12, and 24
Title
Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time Frame
Weeks 4, 8, 12, and 24
Title
Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time Frame
Weeks 4, 8, 12, and 24
Title
Absolute Number of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time Frame
Weeks 4, 8, 12, and 24
Title
Change From Baseline of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time Frame
Baseline, Weeks 4, 8, 12, and 24
Title
Cumulative Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Description
Cumulative number will be calculated as the sum of the number of new or enlarging T2 hyperintense lesions through Weeks 4, 8, 12, and 24.
Time Frame
Weeks 4, 8, 12, and 24
Title
Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Time Frame
Weeks 4, 8, 12, and 24
Title
Change From Baseline of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Time Frame
Baseline, Weeks 4, 8, 12, and 24
Title
Annualized Relapse Rate
Description
Multiple sclerosis (MS) relapse is defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. ARR is defined as the total number of relapses divided by the total participant-time at risk of relapse.
Time Frame
Week 24
Title
Time to First Relapse
Description
MS relapse is defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. Time to first MS relapse will be calculated as the date from first study drug administration through the date of the first relapse, if applicable.
Time Frame
Up to Week 24
Title
Number of Participants With Expanded Disability Status Scale (EDSS) Improvement and Stable Disease and Worsening at Weeks 12, and 24
Description
The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Stable disease is defined as +/- 0.5 change of EDSS. Worsening is > 0.5 increase of EDSS.
Time Frame
Baseline, Weeks 12, and 24
Title
Trough Serum Natalizumab Concentration (Ctrough)
Time Frame
Pre dose on Baseline, Weeks 4, 8, 12, and 24
Title
Trough alpha 4 (α4) Integrin Saturation
Time Frame
Pre dose on Baseline, Weeks 4, 8, 12, and 24
Title
Change From Baseline in Lymphocyte Subsets Count
Description
Lymphocyte subsets include T cells, B cells and natural killer cells (cluster of differentiate 4 [CD4], CD8, CD19, and CD56).
Time Frame
Baseline up to Week 24
Title
Change From Baseline in Anti-Natalizumab Antibodies
Time Frame
Pre dose on Baseline, Weeks 12, and 24
Title
Persistence of Anti-Natalizumab Antibodies
Description
Re-test will be done for antibodies after 6 weeks of first positive result.
Time Frame
Re-test after 6 weeks of first positive result (up to Week 24)
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Time Frame
Up to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnosis of RRMS according to the McDonald criteria
Treatment-naïve in respect to natalizumab as disease modifying monotherapy for RRMS
No or not more than one prior MS disease-modifying therapy
Highly active RRMS, as defined by at least one relapse in the previous year and at least one T1 gadolinium-enhancing lesion or ≥3 new or enlarging T2 lesions
EDSS score ≤ 5.5 at Screening
Estimated glomerular filtration rate (eGFR) >30 millilitre per min (mL/min), as estimated using the Cockcroft-Gault formula.
Key Exclusion Criteria:
Primary- and secondary-progressive MS
Participants for whom MRI is contraindicated
History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study
History of severe allergic or anaphylactic reactions or known hypersensitivity to any antibody drug therapy.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US Biogen Clinical Trial Center
Phone
866-633-4636
Email
clinicaltrials@biogen.com
First Name & Middle Initial & Last Name or Official Title & Degree
Global Biogen Clinical Trial Center
Email
clinicaltrials@biogen.com
Facility Information:
Facility Name
Neurologische Praxis Dr. med. Boris-Alexander Kallmann
City
Bamberg
ZIP/Postal Code
96052
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Phone
+4995196430147
First Name & Middle Initial & Last Name & Degree
Boris Kallmann
Facility Name
Neurologische Studiengesellschaft Bonn GbR
City
Bonn
ZIP/Postal Code
53111
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Phone
+49228677842
First Name & Middle Initial & Last Name & Degree
Stephan Schmidt
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Learn more about this trial
A Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
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