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

Sponsor

Melinda Magyari (Other)

Overall Status

Completed

CT.gov ID

NCT01171209

Collaborator

University of Copenhagen (Other)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Interferon-beta and human leukocyte Interferon-α	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IFN-alfa One single injection of human leukocyte IFN-α (Multiferon® ) 6 MIU s.c.	Drug: Interferon-beta and human leukocyte Interferon-α 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. Other Names: IFN-beta : Rebif, Betaferon IFN-alfa: Multiferon®
Experimental: Interferon-beta One single injection of IFN-beta followed by blood test for MxA9.12 hours after injection	Drug: Interferon-beta and human leukocyte Interferon-α 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. Other Names: IFN-beta : Rebif, Betaferon IFN-alfa: Multiferon®

Arm

Intervention/Treatment

Experimental: IFN-alfa

One single injection of human leukocyte IFN-α (Multiferon® ) 6 MIU s.c.

Drug: Interferon-beta and human leukocyte Interferon-α

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.

Other Names:

IFN-beta : Rebif, Betaferon

IFN-alfa: Multiferon®

Experimental: Interferon-beta

One single injection of IFN-beta followed by blood test for MxA9.12 hours after injection

Drug: Interferon-beta and human leukocyte Interferon-α

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.

Other Names:

IFN-beta : Rebif, Betaferon

IFN-alfa: Multiferon®

Outcome Measures

Primary Outcome Measures

In vivo mRNA MxA response [9-12 hours after injection of one dose Interferon-alfa]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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