REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Interferon-beta and human leukocyte Interferon-α


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFN-alfa<br>One single injection of human leukocyte IFN-α (Multiferon® ) 6 MIU s.c. | Drug: Interferon-beta and human leukocyte Interferon-α<br>* One single injection of interferon(IFN)- β and one single injection of human leukocyte IFN-α (Multiferon® ) 6 MIU s.c. with 1-7 days follow-up.<br>* Other names: IFN-alfa: Multiferon®;|
| Experimental: Interferon-beta<br>One single injection of IFN-beta followed by blood test for MxA9.12 hours after injection | Drug: Interferon-beta and human leukocyte Interferon-α<br>* One single injection of interferon(IFN)- β and one single injection of human leukocyte IFN-α (Multiferon® ) 6 MIU s.c. with 1-7 days follow-up.<br>* Other names: IFN-alfa: Multiferon®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In vivo mRNA MxA response | The primary objective of this study is to compare the in vivo mRNA MxA response to IFN-α with the in vivo mRNA MxA response to IFN-β | 9-12 hours after injection of one dose Interferon-alfa | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determining response marker: IL10 | The in vivo response to IFN-α of known IFN response marker: interleukin-10 (IL10), | 9-12 hours after adminstration of Interferon-alfa | 
| Determining response marker:TRAIL | Determining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) | 9-12 hours after administration of IFN-alfa | 
| Determining response marker IFI27 | Determining IFN-α-inducible protein 27 (IFI27), | 9-12 timer after administration of IFN-alfa | 
| Determining response marker:CXCL10 at mRNA level | Determining :Chemokine CXCL10 at mRNA level | 9-12 hours after IFN-alfa administration | 
| Changes i Neutralizing antibodies Nabs | Measuring changes in Neutralising antibodies 9-12 hours after treatment with one dose IFN-alfa | 9-12 hours after administration of IFN-alfa | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS