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

NCT ID: NCT01171209

Last Updated: 2012-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2011-08-31

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.

Conditions

Multiple Sclerosis

Keywords

MS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IFN-alfa

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

Group Type: EXPERIMENTAL

Interferon-beta and human leukocyte Interferon-α

Intervention Type: DRUG

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.

Interferon-beta

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

Group Type: EXPERIMENTAL

Interferon-beta and human leukocyte Interferon-α

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

IFN-beta : Rebif, Betaferon; IFN-alfa: Multiferon®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Melinda Magyari

OTHER

Sponsor Role: lead

Responsible Party

Melinda Magyari

M.D.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Melinda Magyari, M.D.

Role: PRINCIPAL_INVESTIGATOR

Danish Multiple Sclerosis Research Center

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 25877635 (View on PubMed)

Other Identifiers

2009-016824-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2009-016824-29

Identifier Type: -

Identifier Source: org_study_id