Natalizumab De-escalation With Interferon Beta-1b

NCT01144052 | Completed Phase 4 Results DMC

• 1 other identifier: EOC.NC.09.01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsing-remitting Multiple Sclerosis

Keywords

Natalizumab; Interferon-beta 1b; De-escalation; Ticino

Outcome Measures

Primary Outcomes (1)

• Number of Days Until First On-study Relapse

  Patients were followed-up during 12 months and time to first on-study relapse from randomization was recorded.

  12 months

Secondary Outcomes (7)

• Number of Participants With Relapses

  12 months

• Number of Relapses

  12 months

• Proportion of Relapse Free Patients

  12 months

• Severity of Relapses

  12 months vs baseline

• MRI Parameters

  12 months

Study Arms (2)

Natalizumab

ACTIVE COMPARATOR

Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.

Drug: Natalizumab

Interferon-beta-1b

EXPERIMENTAL

250 mcg (8 MIU) subcutaneous injections every other day

Drug: interferon beta-1b

Interventions

interferon beta-1b DRUG

Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 month at study entry. After a wash-out period of one month, interferon-beta-1b will be administered subcutaneously every other day as indicated by the manufacturers' instructions including the stepwise up-titration scheme as recommended for treatment start. The final dose of interferon beta-1b is 250 mcg (8 million International Units \[MIU\])

Also known as: Betaferon®

Interferon-beta-1b

Natalizumab DRUG

Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.

Also known as: Tysabri

Natalizumab

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Claudio Gobbi: lead
• Ospedale Civico, Lugano: collaborator

Study Sites (1)

Neurocenter of Southern Switzerland, Ospedale Civico Lugano

Lugano, Canton Ticino, 6900, Switzerland

Location

Related Publications (10)

• 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. doi: 10.1007/s00415-008-0061-1. Epub 2008 Oct 29.

  PMID: 19005625 BACKGROUND

• 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. doi: 10.1056/NEJMoa044396.

  PMID: 16510745 BACKGROUND

• 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. doi: 10.1056/NEJMoa044397.

  PMID: 16510744 BACKGROUND

• 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.

  PMID: 11902592 BACKGROUND

• 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.

  PMID: 11902589 BACKGROUND

• 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. doi: 10.1016/j.jns.2009.06.004. Epub 2009 Jun 26.

  PMID: 19560168 BACKGROUND

• Ransohoff RM. Natalizumab and PML. Nat Neurosci. 2005 Oct;8(10):1275. doi: 10.1038/nn1005-1275. No abstract available.

  PMID: 16189528 BACKGROUND

• Sadovnick AD, Ebers GC. Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci. 1993 Feb;20(1):17-29. doi: 10.1017/s0317167100047351.

  PMID: 8467424 BACKGROUND

• Gobbi C, Meier DS, Cotton F, Sintzel M, Leppert D, Guttmann CR, Zecca C. Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial. BMC Neurol. 2013 Aug 2;13:101. doi: 10.1186/1471-2377-13-101.

  PMID: 23915113 RESULT

• Zecca C, Riccitelli GC, Calabrese P, Pravata E, Candrian U, Guttmann CR, Gobbi C. Treatment satisfaction, adherence and behavioral assessment in patients de-escalating from natalizumab to interferon beta. BMC Neurol. 2014 Feb 28;14:38. doi: 10.1186/1471-2377-14-38.

  PMID: 24576156 RESULT

Related Links

• Homepage of the hospital organisation in Ticino
• Homepage of the Swiss Society of Multiple Sclerosis

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Interferon beta-1b; Natalizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Claudio Globbi, Dr. med.
• Organization: Ospedale Civico

claudio.gobbi@eoc.ch

+41 91 811 6921

Study Officials

• Claudio Gobbi, Dr med.

  Neurocenter of Southern Switzerland, Ospedale Civico Lugano

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 15, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: April 17, 2014
• Results First Posted: April 17, 2014

Record last verified: 2014-03

Locations

CH (1)