Clinical trial NCT01171209: REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients
Official title: REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: MS
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2010-07-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine if Interferon-alfa is effective and safe in multiple sclerosis patients who developed neutralizing antibodies for Interferon-beta.

Detailed description: Patient with NAbs developed during IFN-β therapy do not have any longer beneficial effect of any IFN-β preparation and IFN-β has to be replaced with another therapy that may be less effective or carry along serious adverse effects. Hence, many NAb positive patients wish to continue IFN therapy, and these patients might benefit from treatment with IFN-α as both IFN-α and IFN-β are type I interferons that bind to the same interferon receptor (IFNAR). A full in vivo response to human IFN-α (Multiferon) comparable to that seen after IFN-β induction would suggest that the same therapeutic effect could be obtained with human IFN-α (Multiferon).We measure in vivo response of MxA 9-12 hours after administration of human IFN-α (Multiferon) and four other known IFN response markers measured with rt-PCR.

As controls, NAb negative MS patients with a full in vivo MxA response will be studied.

Eligibility criteria: Inclusion Criteria:

* The subject must give written informed consent prior to any study related activities
* Subject age must be between 18 and 55 (both included)
* The subject must have MS according to McDonald criteria
* The subject must have disability equivalent to EDSS of 5.5 or less
* The subject must have been treated with any IFN-β preparation for at least 12 months at any time
* The subject must have been shown to be NAb positive and without no in vivo mRNA MxA response within the last 12 months
* The subject must be prepared and considered able to follow the protocol

Exclusion Criteria:

* The subject must not have conditions that might give rise to similar symptoms as MS
* The subject must not have received any immunomodulatory or immunosuppressive treatment (other than IFN-β or glatiramer acetate) 6 months prior to the screening visit
* The subject must not have received mitoxantrone, cyclophosphamide, treosulphane, natalizumab, daclizumab, rituximab, alemtuzumab, cladribine, or any experimental therapy at any time
* The subject must not have undergone previous total body irradiation, total lymphoid irradiation, stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
* The subject must not have received treatment with glucocorticoids or ATCH later than 2 month prior to the screening visit
* The subject must not have alcohol and drug dependency
* The subject must not have cardiac or renal insufficiency
* The subject must not have any systemic disease that can influence the subject's safety or compliance
* Subjects may be male or female. Women of child-bearing potential must be sexually inactive or practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or IUD with spermicide)
* The subject must not have known or suspected allergy to IFN-α
* The subject must not have participated in any other study within 3 months prior to the screening visit

Primary outcomes:
measure: In vivo mRNA MxA response
timeFrame: 9-12 hours after injection of one dose Interferon-alfa
Secondary outcomes:
measure: Determining response marker: IL10
timeFrame: 9-12 hours after adminstration of Interferon-alfa
measure: Determining response marker:TRAIL
timeFrame: 9-12 hours after administration of IFN-alfa
measure: Determining response marker IFI27
timeFrame: 9-12 timer after administration of IFN-alfa
measure: Determining response marker:CXCL10 at mRNA level
timeFrame: 9-12 hours after IFN-alfa administration
measure: Changes i Neutralizing antibodies Nabs
timeFrame: 9-12 hours after administration of IFN-alfa
Other outcomes:
Locations:
Study officials:
affiliation: Danish Multiple Sclerosis Research Center
name: Melinda Magyari, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magyari M, Bach Sondergaard H, Sellebjerg F, Soelberg Sorensen P. Preserved in vivo response to interferon-alpha in multiple sclerosis patients with neutralising antibodies against interferon-beta (REPAIR study). Mult Scler Relat Disord. 2013 Apr;2(2):141-6. doi: 10.1016/j.msard.2012.10.001. Epub 2012 Dec 11.