Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis: A Swiss Multicenter Study Prospective, Controlled, Single-arm, Open-label, Multi-centre, Phase IV Study
Overview
- Phase
- Phase 4
- Intervention
- Interferon beta-1b
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Sponsor
- Claudio Gobbi
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Annualized relapse rate on study compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment (month -24 to -12)
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
Multiple Sclerosis (MS) is the most common neurological disorder causing disability in young adults affecting approximately 1 in 1.000 people in western countries. The clinical manifestations usually begin at the age of 20 to 40 years with a median age of 28 years at onset with acute episodes of neurological dysfunction, followed by periods of partial or complete remission and clinical stability in between relapses. This relapsing-remitting phase (RR-MS) of the disease is usually followed by progressive clinical disability (secondary progressive phase, SP-MS).
At present, there is no cure for MS. Based on the pathological concept that neuroinflammation is the common element leading or contributing to neurodegenerative changes, immune interventions have been introduced into clinical practice such as Natalizumab (Tysabri), a humanized monoclonal antibody. Natalizumab (Tysabri) is indicated as a disease-modifying monotherapy of highly active relapsing MS. The associated risks, especially progressive multifocal leukoencephalopathy, necessitate active monitoring of patients and a continuous discussion of optimum use of this drug. In clinical practice, the question how to manage patients on natalizumab at a higher risk for progressive multifocal leukoencephalopathy remains unresolved.
This prospective, controlled (comparison to the period prior to natalizumab treatment), single-arm, open-label, multi-centre, phase IV study aims to evaluating 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 evaluating if interferon beta-1b treatment may be able to overcome the recurrence of significant clinical and radiological disease activity after natalizumab cessation and may keep disease activity better under control as compared to the time prior to natalizumab.
The study population includes patients with relapsing-remitting multiple sclerosis (RR-MS) being treated at least for 12 months with natalizumab and having decided to stop natalizumab treatment and to de-escalate their therapy to a first line treatment with interferon beta-1b. They will be treated during 12 months with interferon-beta 1b 250 mcg given subcutaneously every other day. A 12-month follow-up period with the same treatment is planned.
Investigators
Claudio Gobbi
Dr. med.
Ospedale Civico, Lugano
Eligibility 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
- •6-18 months prior to natalizumab-treatment
- •at natalizumab start
- •12 months after natalizumab initiation;
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;
Arms & Interventions
Interferon beta-1b
Interferon beta-1b 250 mcg s.c. every other day
Intervention: Interferon beta-1b
Outcomes
Primary Outcomes
Annualized relapse rate on study compared to annualized relapse rate in the year prior to natalizumab initiation on first line disease modifying treatment (month -24 to -12)
Time Frame: 24 months
Secondary Outcomes
- Severity of relapses(24 months)
- Proportion of relapse free patients(24 months)
- 3-month confirmed EDSS progression(24 months)
- MSFC(15 months)
- Change of EDSS score compared to change in the year prior to natalizumab treatment (month -24 to-12(12 months)
- Change of MSFC score compared to change in the year prior to natalizumab treatment (month -24 to-12(12 months)
- Number of new/enlarging T2-hyperintense lesions(24 months)
- Number of Gd-enhancing lesions(24 months)
- EQ-5D(18 months)
- FAMS(18 months)