Phase 4
N=19
Natalizumab De-escalation With Interferon Beta-1b
Relapsing-remitting Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT01144052 ↗Enrolled (actual)
19
Serious AEs
5.3%
Results posted
Apr 2014
Primary outcome: Primary: Number of Days Until First On-study Relapse — NA; 103 days — p=0.125
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- interferon beta-1b (Drug); Natalizumab (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Claudio Gobbi
- Primary completion
- Nov 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Days Until First On-study Relapse |
NA; 103 | 0.125 |
| SECONDARY Number of Participants With Relapses |
0; 2 | 0.447 |
| SECONDARY Number of Relapses |
0; 3 | 0.447 |
| SECONDARY Proportion of Relapse Free Patients |
10; 7 | 0.206 |
| SECONDARY Severity of Relapses |
0; 0.5 | — |
| SECONDARY MRI Parameters |
0; 0.5; 0; 1.5; 0; 0.5 | 0.234 |
| SECONDARY Number of Patients With Adverse Events |
7; 4; 0; 4 | — |
| SECONDARY Number of Infections |
25; 8 | — |
Summary
Multiple Sclerosis (MS) is the most common neurological disorder causing disability in young adults. The management of MS-patients requires treatment with disease-modifying agents, monoclonal antibodies such as natalizumab or immunosuppressants. Natalizumab showed good efficacy and is approved for treatment of relapsing MS with a number of restrictions due to safety issues. Cognitive data related to natalizumab treatment are still scarce. Interferon-beta-1b is approved for high-frequency, subcutaneous (sc) administration in the treatment of multiple sclerosis. It reduces the relapse rate, severity, hospitalisation and the disease activity as seen on MRI.
This is a pilot study to explore the concept of de-escalating natalizumab treatment to interferon-beta-1b e.o.d compared to continuous treatment with natalizumab in patients with relapsing-remitting multiple sclerosis previously treated with natalizumab for 12 months. The study is designed as prospective, controlled, randomized, rater-blinded, parallel-group, two arm, mono-centric including patients of the Ticino Cohort. One arm will be treated with Interferon-beta 1b 250mcg given subcutaneously every other day, the other with Natalizumab 300 mg given intravenously (i.v.), every four weeks. The treatment duration is 12 months, the follow-up period 12 months. The time to first on-study relapse will be compared between the to treatment arms (primary outcome). Other efficacy parameter include clinical and radiological parameters, patient reported outcome on quality of life and fatigue. Safety is assessed by reports of adverse events.
Eligibility Criteria
Inclusion Criteria
- Female or male patients with relapsing-remitting forms of multiple sclerosis (according to McDonald's criteria)
- Age between 18 and 60 years
- Natalizumab-treatment for at least 12 month following the current Swiss guidelines for treatment initiation
- Eligible patients are clinically stable (free from relapses and 6-month confirmed disability progression for at least 6 months) while on natalizumab-treatment
- Women of potential childbearing with active contraceptive methods
- Patients who are willing to undergo study procedures
- Patients who are willing and able to sign informed consent
Exclusion Criteria
- Patients who have previously entered this study
- Natalizumab-treatment for less than 12 month following the current Swiss guidelines for treatment initiation
- Sign of clinical disease activity within the 6 month
- One or more relapses and/or 6-month confirmed disability progression during the 6 months prior to the study
- Any disease other than multiple sclerosis that would better explain the patient's signs and symptoms
- Secondary progressive MS
- Primary progressive MS
- Pregnancy - Urine pregnancy test at baseline visit - 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
- Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol
Data sourced from ClinicalTrials.gov (NCT01144052). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.