Natalizumab De-escalation With Interferon Beta-1b

Condition(s) targeted: Relapsing-Remitting Multiple Sclerosis; Clinically Stable

Intervention: interferon beta-1b (Drug); Natalizumab (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Ospedale Civico, Lugano

Official(s) and/or principal investigator(s):
Claudio Gobbi, Dr med., Principal Investigator, Affiliation: Neurocenter of Southern Switzerland, Ospedale Civico Lugano

Overall contact:
Claudio Gobbi, Dr med., Phone: +41 91 811 6469, Email: claudio.gobbi@eoc.ch

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.

Official title: De-escalation After Natalizumab Treatment With Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis

Study design: Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Time to first on-study relapse

Secondary outcome:

Clinical parameters

Multiple sclerosis functional composite score

Cognitive functioning

MRI parameters

Quality of life

Fatigue

Vital signs

Vital signs

Functional assessment multiple sclerosis (FAMS)

Adverse events

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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

Claudio Gobbi, Dr med., Phone: +41 91 811 6469, Email: claudio.gobbi@eoc.ch

Neurocenter of Southern Switzerland, Ospedale Civico Lugano, Lugano, Ticino 6900, Switzerland; Recruiting
Claudio Gobbi, Dr med., Phone: +41 811 91 6479, Email: claudio.gobbi@eoc.ch
Chiara Zecca, Dr med., Phone: +41 811 91 6604, Email: chiara.zecca@eoc.ch
Ursula Candrian, Dr med., Sub-Investigator

Homepage of the hospital organisation in Ticino

Homepage of the Swiss Society of Multiple Sclerosis

Related publications:

Multiple Sclerosis Therapy Consensus Group (MSTCG); Wiendl H, Toyka KV, Rieckmann P, Gold R, Hartung HP, Hohlfeld R. Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol. 2008 Oct;255(10):1449-63. Epub 2008 Oct 29.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA, Sandrock AW; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):911-23.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910.

IFNB Multiple Sclerosis Study Group. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. 1993 [classical article] Neurology. 2001 Dec;57(12 Suppl 5):S3-9. No abstract available.

Paty DW, Li DK; UBC MS/MRI Study Group and IFNB Multiple Sclerosis Study Group. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. 1993 [classical article] Neurology. 2001 Dec;57(12 Suppl 5):S10-5. No abstract available.

Putzki N, Yaldizli O, Tettenborn B, Diener HC. Multiple sclerosis associated fatigue during natalizumab treatment. J Neurol Sci. 2009 Oct 15;285(1-2):109-13. Epub 2009 Jun 26.

Ransohoff RM. Natalizumab and PML. Nat Neurosci. 2005 Oct;8(10):1275. No abstract available.

Sadovnick AD, Ebers GC. Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci. 1993 Feb;20(1):17-29. Review.

Starting date: June 2010
Last updated: June 14, 2010