Natalizumab de-escalation to interferon-beta-1b in patients with relapsing-remitting multiple sclerosis: A multicenter study

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-004040-30-AT

Enrollment

Registered

2013-03-12

Start date

2013-05-24

Completion date

Unknown

Last updated

2026-04-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

relapse-remitting multiple sclerosis

Interventions

Trade Name: BETAFERON® (interferon beta-1b) Product Name: Betaferon Pharmaceutical Form: Powder and solution for solution for injection INN or Proposed INN: Betaferon CAS Number: 145155-23-3 Other des

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: · Female or male patients with relapsing-remitting forms of multiple sclerosis (according to McDonald's criteria); · Age between 18 and 70 years; · Natalizumab-treatment for at least 12 months following the current Swiss guidelines for treatment initiation; · Treated with a disease-modifying therapy other than interferon beta-1b for at least 12 months before natalizumab was initiated; · Never treated with interferon beta-1b; · Eligible patients are clinically stable (free from relapses and 6-month confirmed disability progression for at least 6 months) while on natalizumab-treatment and do not show any Gd-enhancement on their last MRI performed while on Tysabri; · In eligible patients MRI were performed in the past as following a) 6-18 months prior to natalizumab-treatment b) at natalizumab start c) 12 months after natalizumab initiation; · Good records with regard to clinical disease activity (relapse rate, EDSS progression) in the year prior to natalizumab and during natalizumab; · Patients who decide to stop natalizumab treatment after a careful benefit/risk assessment. Risk for PML increases with duration of natalizumab exposure, pretreatment with an immunosuppressant agent or serological status of anti-JC-virus positivity; · Patients, who in context with cessation of natalizumab have decided, after a careful benefit/risk assessment, to continue treatment of their MS with Interferon beta-1b; · Women of potential childbearing with active contraceptive methods; · Patients who are willing to undergo study procedures; · Patients who are willing to undergo MRI; · Patients who are willing and able to sign informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36

Exclusion criteria

Exclusion criteria: · Patients who have previously entered this study; · Natalizumab-treatment for less than 12 months following the current Swiss guidelines for treatment initiation; · Prior treatment with interferon beta-1b (ever interferon beta-1b); · Sign of clinical disease activity within the 6 months; · One or more relapses and/or 6-month confirmed disability progression during the 6 months prior to the study; · Secondary progressive MS; · Primary progressive MS; · Pregnancy - Serum pregnancy test at screening visit positive- or breast feeding; · Uncontrolled, clinically significant heart diseases, such as arrhythmias, angina, or uncompensated congestive heart failure; · History of severe depression or attempted suicide or current suicidal ideation; · Medical or psychiatric conditions that compromise the ability to give informed consent, to comply with the protocol, or to complete the study; · Uncontrolled seizure disorder; · Myopathy or clinically significant liver disease; · Inability, in the opinion of the principal investigator or staff, to comply with protocol requirements for the duration of the study; · Known hypersensitivity to interferon-beta or other human proteins including albumin; · Any contraindication for MRI or contrast administration; · A history of drug abuse in the 6 months prior to screening; · Treatment with any of the following in the 30 days before day 1: systemic corticosteroids, ACTH, or other investigational drugs; · Participation in any other study involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study; · Current participation on other clinical trials; · Treatment with drugs which might interfere with the evaluation of study drugs during the study protocol such as immunomodulants, immunosuppressives other than interferon beta-1b; · Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol such as immunomodulants, immunosuppressives other than interferon beta-1b.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the concept of natalizumab de-escalation to interferon-beta-1b e.o.d in relapsing-remitting multiple sclerosis patients, who consider stopping natalizumab due to a benefit-risk assessment. In particular, to evaluate if interferon beta-1b treatment may be able to overcome the recurrence of significant clinical and radiological disease activity after natalizumab cessation and keep disease activity better under control as compared to the time prior to natalizumab.;Secondary Objective: not applicable;Primary end point(s): Primary endpoint: Annualized relapse rate on study after treatment with interferon beta 1b compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment.;Timepoint(s) of evaluation of this end point: Primary endpoint: Annualized relapse rate on study after 12 months of treatment with interferon beta 1b (Assessments: Day 1, month 3, 6, 9, 12) compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment (month -24 to -12).	—

Measure

Time frame

Main Objective: To evaluate the concept of natalizumab de-escalation to interferon-beta-1b e.o.d in relapsing-remitting multiple sclerosis patients, who consider stopping natalizumab due to a benefit-risk assessment. In particular, to evaluate if interferon beta-1b treatment may be able to overcome the recurrence of significant clinical and radiological disease activity after natalizumab cessation and keep disease activity better under control as compared to the time prior to natalizumab.;Secondary Objective: not applicable;Primary end point(s): Primary endpoint: Annualized relapse rate on study after treatment with interferon beta 1b compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment.;Timepoint(s) of evaluation of this end point: Primary endpoint: Annualized relapse rate on study after 12 months of treatment with interferon beta 1b (Assessments: Day 1, month 3, 6, 9, 12) compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment (month -24 to -12).

—

Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints: 1) Change of clinical parameters (severity of relapses by functional system score, proportion of relapse-free patients), 3-month confirmed EDSS progression (of at least 1.0 points if score < 5.5, at least 0.5 points if score = 5.5), MSFC compared to baseline. 2) Change of EDSS, MSFC scores from baseline to 12 months compared to the changes in the year prior to natalizumab treatment. 3) MRI parameters (number of new T2-hyperintense lesions, number of Gd-enhancing lesions on T1-weighted images) with subtraction MRI. 4) Patient reported outcome: Quality of life using EQ-5D, Functional assessment of multiple sclerosis (FAMS).;Timepoint(s) of evaluation of this end point: Secondary endpoints: Change of clinical parameters (severity of relapses by functional system score, proportion of relapse-free patients), 3-month confirmed EDSS progression (of at least 1.0 points if score < 5.5, at least 0.5 points if score = 5.5), MSFC at months 3, 6, 9, 12, 15, 18, 21, 24 compared to baseline (Day 1). Change of EDSS, MSFC scores from baseline to 12 months compared to the changes in the year prior to natalizumab treatment (month -24 to -12). MRI parameters (number of new T2-hyperintense lesions, number of Gd-enhancing lesions on T1-weighted images) with subtraction MRI at months 6,12, 24. Patient reported outcome Quality of life using EQ-5D, Functional assessment	—

Measure

Time frame

Secondary end point(s): Secondary endpoints: 1) Change of clinical parameters (severity of relapses by functional system score, proportion of relapse-free patients), 3-month confirmed EDSS progression (of at least 1.0 points if score < 5.5, at least 0.5 points if score = 5.5), MSFC compared to baseline. 2) Change of EDSS, MSFC scores from baseline to 12 months compared to the changes in the year prior to natalizumab treatment. 3) MRI parameters (number of new T2-hyperintense lesions, number of Gd-enhancing lesions on T1-weighted images) with subtraction MRI. 4) Patient reported outcome: Quality of life using EQ-5D, Functional assessment of multiple sclerosis (FAMS).;Timepoint(s) of evaluation of this end point: Secondary endpoints: Change of clinical parameters (severity of relapses by functional system score, proportion of relapse-free patients), 3-month confirmed EDSS progression (of at least 1.0 points if score < 5.5, at least 0.5 points if score = 5.5), MSFC at months 3, 6, 9, 12, 15, 18, 21, 24 compared to baseline (Day 1). Change of EDSS, MSFC scores from baseline to 12 months compared to the changes in the year prior to natalizumab treatment (month -24 to -12). MRI parameters (number of new T2-hyperintense lesions, number of Gd-enhancing lesions on T1-weighted images) with subtraction MRI at months 6,12, 24. Patient reported outcome Quality of life using EQ-5D, Functional assessment

—

Countries

Austria, Switzerland

Contacts

Public ContactDepartment of Neurology

Ospedale Regionale di Lugano

0043918116474

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Apr 23, 2026