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

This study has been completed.
Sponsor:
Collaborator:
University of Copenhagen
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01171209
First received: July 8, 2010
Last updated: August 8, 2011
Last verified: May 2010
History of Changes
  Purpose

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 Intervention Phase
Multiple Sclerosis
 Drug: Interferon-beta and human leukocyte Interferon-α
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • In vivo mRNA MxA response [ Time Frame: 9-12 hours after injection of one dose Interferon-alfa ] [ Designated as safety issue: No ]
    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 [ Time Frame: 9-12 hours after adminstration of Interferon-alfa ] [ Designated as safety issue: No ]
    The in vivo response to IFN-α of known IFN response marker: interleukin-10 (IL10),

  • Determining response marker:TRAIL [ Time Frame: 9-12 hours after administration of IFN-alfa ] [ Designated as safety issue: No ]
    Determining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

  • Determining response marker IFI27 [ Time Frame: 9-12 timer after administration of IFN-alfa ] [ Designated as safety issue: No ]
    Determining IFN-α-inducible protein 27 (IFI27),

  • Determining response marker:CXCL10 at mRNA level [ Time Frame: 9-12 hours after IFN-alfa administration ] [ Designated as safety issue: No ]
    Determining :Chemokine CXCL10 at mRNA level

  • Changes i Neutralizing antibodies Nabs [ Time Frame: 9-12 hours after administration of IFN-alfa ] [ Designated as safety issue: No ]
    Measuring changes in Neutralising antibodies 9-12 hours after treatment with one dose IFN-alfa


Enrollment: 10
Study Start Date: July 2010
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IFN-alfa
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.
 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®

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 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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01171209

Sponsors and Collaborators
Rigshospitalet, Denmark
University of Copenhagen
Investigators
Principal Investigator: Melinda Magyari, M.D. Danish Multiple Sclerosis Research Center
  More Information

No publications provided

Responsible Party: Prof. Per Soelberg Sorensen, M.D, Danish MS Research Center
ClinicalTrials.gov Identifier: NCT01171209     History of Changes
Other Study ID Numbers: 2009-016824-29, 2009-016824-29
Study First Received: July 8, 2010
Last Updated: August 8, 2011
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by Rigshospitalet, Denmark:
MS

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-alpha
Interferon Alfa-2a
Interferon-beta
Interferons
 Antibodies
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 17, 2012