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

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Interferon-beta and human leukocyte Interferon-α

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring MS

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

IFN-alfa

Interferon-beta

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Determining response marker: IL10

The in vivo response to IFN-α of known IFN response marker: interleukin-10 (IL10),

Determining response marker:TRAIL

Determining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Determining response marker IFI27

Determining IFN-α-inducible protein 27 (IFI27),

Determining response marker:CXCL10 at mRNA level

Determining :Chemokine CXCL10 at mRNA level

Changes i Neutralizing antibodies Nabs

Measuring changes in Neutralising antibodies 9-12 hours after treatment with one dose IFN-alfa

Full Information

NCT ID

NCT01171209

First Posted

July 8, 2010

Last Updated

November 29, 2012

Sponsor

Melinda Magyari

Collaborators

University of Copenhagen

1. Study Identification

Unique Protocol Identification Number

NCT01171209

Brief Title

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

Acronym

REPAIR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2012

Overall Recruitment Status

Completed

Study Start Date

July 2010 (undefined)

Primary Completion Date

June 2011 (Actual)

Study Completion Date

August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Melinda Magyari

Collaborators

University of Copenhagen

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IFN-alfa

Arm Type

Experimental

Arm Description

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

Arm Title

Interferon-beta

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Interferon-beta and human leukocyte Interferon-α

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

In vivo mRNA MxA response

Description

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

Time Frame

9-12 hours after injection of one dose Interferon-alfa

Secondary Outcome Measure Information:

Title

Determining response marker: IL10

Description

The in vivo response to IFN-α of known IFN response marker: interleukin-10 (IL10),

Time Frame

9-12 hours after adminstration of Interferon-alfa

Title

Determining response marker:TRAIL

Description

Determining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Time Frame

9-12 hours after administration of IFN-alfa

Title

Determining response marker IFI27

Description

Determining IFN-α-inducible protein 27 (IFI27),

Time Frame

9-12 timer after administration of IFN-alfa

Title

Determining response marker:CXCL10 at mRNA level

Description

Determining :Chemokine CXCL10 at mRNA level

Time Frame

9-12 hours after IFN-alfa administration

Title

Changes i Neutralizing antibodies Nabs

Description

Measuring changes in Neutralising antibodies 9-12 hours after treatment with one dose IFN-alfa

Time Frame

9-12 hours after administration of IFN-alfa

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melinda Magyari, M.D.

Organizational Affiliation

Danish Multiple Sclerosis Research Center

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

25877635

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.

Results Reference

derived

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

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