Multiple Sclerosis, Relapsing-RemittingPhase 4NCT05532163
A Study to Investigate the Radiological Onset of Action After Treatment Initiation With Subcutaneous (SC) Natalizumab in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
A Phase 4 study testing Natalizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Biogen at 2 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesGermany
- Study dates
- 23 Jan 2023to 9 Oct 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Neurologische Praxis Dr. med. Boris-Alexander Kallmann
Bamberg, 96052
Neurologische Studiengesellschaft Bonn GbR
Bonn, 53111
About this study
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)
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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Natalizumab
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NatalizumabDrug
Also called Tysabri, BG00002
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| Natalizumab | Experimental | Participants will receive natalizumab 300 milligrams (mg) (2*150 mg), SC injection, once every 4 weeks (Q4W) up to Week 24. Receives: Drug: Natalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to Week 24
Secondary outcomes (20)
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.
Measured: Weeks 4, 8, and 12
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.
Measured: Weeks 4, 8, 12, and 24
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.
Measured: Baseline, Weeks 4, 8, 12, and 24
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.
Measured: Weeks 4, 8, 12, and 24
Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Measured: Weeks 4, 8, 12, and 24
Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Measured: Weeks 4, 8, 12, and 24
Absolute Number of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Measured: Weeks 4, 8, 12, and 24
Change From Baseline of Any (New or Persisting) Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Measured: Baseline, 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.
Measured: Weeks 4, 8, 12, and 24
Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Measured: Weeks 4, 8, 12, and 24
Change From Baseline of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Measured: Baseline, 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.
Measured: Week 24
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.
Measured: Up to Week 24
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.
Measured: Baseline, Weeks 12, and 24
Trough Serum Natalizumab Concentration (Ctrough)
Measured: Pre dose on Baseline, Weeks 4, 8, 12, and 24
Trough alpha 4 (α4) Integrin Saturation
Measured: Pre dose on Baseline, Weeks 4, 8, 12, and 24
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).
Measured: Baseline up to Week 24
Change From Baseline in Anti-Natalizumab Antibodies
Measured: Pre dose on Baseline, Weeks 12, and 24
Persistence of Anti-Natalizumab Antibodies
Re-test will be done for antibodies after 6 weeks of first positive result.
Measured: Re-test after 6 weeks of first positive result (up to Week 24)
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.
Measured: Up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start23 Jan 2023
- Primary completion9 Oct 2023
- Study completion9 Oct 2023
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05532163
- Sponsor's protocol ID
- DE-TYS-12072
- Other IDs
- 2022-001820-14
- Status last verified
- Jun 2024
- First submitted
- 5 Sep 2022
- Last updated
- 21 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05532163
- Acronym / sponsor ID
- DE-TYS-12072
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 9 Oct 2023 (actual)
- Study completion
- 9 Oct 2023 (actual)
- First posted
- 8 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Natalizumab | Experimental | Drug: NatalizumabParticipants will receive natalizumab 300 milligrams (mg) (2*150 mg), SC injection, once every 4 weeks (Q4W) up to Week 24. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NatalizumabAlso: Tysabri, BG00002Administered as specified in the treatment arm | Drug | Natalizumab |
Primary outcome
Cumulative Number of Active Lesions (CUALs) Through Week 24
Time frame: Up to 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).
20 secondary outcomes
Cumulative Number of CUALs Through Weeks 4, 8, and 12
Time frame: Weeks 4, 8, and 12
Absolute Number of CUALs at Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
Mean Change From Baseline of CUALs at Weeks 4, 8, 12, and 24
Time frame: Baseline, Weeks 4, 8, 12, and 24
Cumulative Number of New Gd-Enhancing Lesions Through Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
Absolute Number of New Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
Absolute Number of Persisting Gd-Enhancing Lesions at Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
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
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
Cumulative Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
Absolute Number of New or Enlarging T2 Lesions at Weeks 4, 8, 12, and 24
Time frame: Weeks 4, 8, 12, and 24
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
Annualized Relapse Rate
Time frame: Week 24
Time to First Relapse
Time frame: Up to Week 24
Number of Participants With Expanded Disability Status Scale (EDSS) Improvement and Stable Disease and Worsening at Weeks 12, and 24
Time frame: Baseline, Weeks 12, and 24
Trough Serum Natalizumab Concentration (Ctrough)
Time frame: Pre dose on Baseline, Weeks 4, 8, 12, and 24
Trough alpha 4 (α4) Integrin Saturation
Time frame: Pre dose on Baseline, Weeks 4, 8, 12, and 24
Change From Baseline in Lymphocyte Subsets Count
Time frame: Baseline up to Week 24
Change From Baseline in Anti-Natalizumab Antibodies
Time frame: Pre dose on Baseline, Weeks 12, and 24
Persistence of Anti-Natalizumab Antibodies
Time frame: Re-test after 6 weeks of first positive result (up to Week 24)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Week 24
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2024.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Natalizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Biogen at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Number of Active Lesions (CUALs) Through Week 24 (time frame: Up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2024.