A Serologic Study to Correlate Beta-IFN NAb Titers to Beta-IFN Induced Biomarker Response in Patients With Multiple Sclerosis

December 20, 2007 updated by: Biogen

Impact of Neutralizing Antibodies on Interferon Responsive Genes Highlights Biomarker Response.

Study Title: A Serologic Study to Correlate b-IFN NAb titers to b-IFN Induced Biomarker Response in Patients with Multiple Sclerosis

Objectives: Subjects currently on any of the three b-IFN preparations (Avonex (Interferon b-1a 30 mcg IM Q 7 days), Rebif (Interferon b-1a 22 or 44mcg SC TIW), or Betaseron (Interferon b-1b 250mcg SC QOD)) will be enrolled to one of 3 groups:

Group 1: Approximately 200 subjects will be enrolled who are NAb+ (titer ³ 20NU/ml) Group 2: Approximately 50 subjects will be enrolled who are BAb- (titer <8U) and NAb- (titer <20 NU/ml) Group 3: Approximately 50 subjects will be enrolled who are BAb+ (titer ³8U) and NAb- (titer <20 NU/ml)

The primary objective of this study is to compare baseline b-IFN induced MxA mRNA response in neutralizing antibody positive (NAb+, titers ³ 20NU/ml, Group 1) vs. antibody negative (NAb-, titers < 20NU/ml, BAb-, titers <8U, Group 2) patients.

Secondary objectives are:

  1. To compare b-IFN induced MxA mRNA response in neutralizing antibody positive (NAb+, titers ³ 20NU/ml, Group 1) vs. antibody negative (NAb-, titers < 20NU/ml, BAb-, titers <8U, Group 2) patients at the month 6 visit.
  2. To compare b-IFN induced biomarker response (viperin, IFIT1) in neutralizing antibody positive (NAb+, titers ³ 20NU/ml, Group 1) vs. antibody negative (NAb-, titers < 20NU/ml, BAb-, titers <8U, Group 2) patients (data compared at baseline and month 6 visits)
  3. To compare b-IFN induced biomarker response (MxA, viperin, IFIT1) in neutralizing antibody positive (NAb+, titers ³ 20NU/ml, Group 1) vs. BAb+ (titers ³8U)/NAb- (titers <20 NU/ml, Group 3) patients at baseline and month 6 visits.
  4. To correlate NAb titer levels with b-IFN induced biomarker response (data taken from baseline and month 6 visits from Group 1).
  5. To compare b-IFN induced biomarker response (MxA, viperin, IFIT1) in BAb-/NAb- patients (Group 2) vs. BAb +/NAb- patients (Group 3) in order to determine if BAbs affect b-IFN induced biomarker response (data compared at baseline and month 6 visits).

Tertiary objectives are:

1. To explore patient characteristics that may predict NAb positivity.

Design: This is a multi-center, open-label study of approximately 300 (200 NAb+ and 100 NAb- (50 BAb+ and 50 BAb-)) MS patients that will compare b-IFN induced biomarker response following b-IFN injection in neutralizing antibody positive vs. antibody negative patients.

Study Population: Approximately 300 subjects (200 in Group 1, 50 in Group 2, and 50 in Group 3) will be recruited for the study.

Inclusion Criteria: To be eligible for entry into this study, candidates must meet all of the following eligibility criteria at the time of randomization:

  1. Patients (male or female) diagnosed with relapsing forms of MS.
  2. Currently being treated with the same b-IFN (in accordance with FDA approved dosing and schedules) for 12 to 48 months inclusive.
  3. All levels of disability
  4. Age 18-65 years inclusive
  5. Subjects must be willing to be followed for the 6-month study period.

Exclusion Criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of study initiation.

  1. Patients with prior b-IFN NAb test (whether positive or negative).
  2. Patients who are currently being treated or have been treated within 6 months prior to screening with combination therapy (b-IFN plus any other immunosuppressant/immunomodulatory) other than IV steroids (either pulse or for a relapse).
  3. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
  4. Any other reasons that, in the opinion of the Investigator, the subject is determined to be unsuitable for enrollment into this study.

Treatment Groups: This is a multi-center, open-label study of approximately 300 (200 NAb+ patients and 100 NAb- patients (50 BAb+ and 50 BAb-)) relapsing MS patients that will compare b-IFN induced biomarker response following b-IFN injection in neutralizing antibody positive vs. antibody negative patients.

Subjects currently on any of the three b-IFN preparations (Avonex (Interferon b-1a 30 mcg IM Q 7 days), Rebif (Interferon b-1a 22 or 44mcg SC TIW), or Betaseron (Interferon b-1b 250mcg SC QOD)) will be enrolled to one of 3 groups:

Group 1: Approximately 200 subjects will be enrolled who are NAb+ (titer ³ 20NU/ml)

Group 2: Approximately 50 subjects will be enrolled who are BAb- (titer <8U) and NAb- (titer <20 NU/ml)

Group 3: Approximately 50 subjects will be enrolled who are BAb+ (titer ³8U) and NAb- (titer <20 NU/ml)

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama - Birmingham
      • Cullman, Alabama, United States, 35058
        • Physicians Resource Network
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
    • California
      • Irvine, California, United States, 92697
        • University of California - Irvine
      • San Francisco, California, United States, 94117
        • University of California San Francisco - MS Center
    • Florida
      • Tampa, Florida, United States, 33609
        • Tampa Neurology
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center, Illinois Neurological Institute
    • Indiana
      • Fort Wayne, Indiana, United States, 46805
        • Fort Wayne Neurological Center
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Mercy Ruan Neurology Clinic
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kentucky Neuroscience Research / University Neurologists, P.S.C
    • Louisiana
      • Shreveport, Louisiana, United States, 71130
        • Louisiana State University Health Sciences Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University
      • St. Louis, Missouri, United States, 63110
        • BJC Medical Group
    • New York
      • White Plains, New York, United States, 10601
        • Family Health Center
    • Ohio
      • Columbus, Ohio, United States, 43221
        • The Multiple Sclerosis Center at the Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Brown University / Rhode Island Hospital
    • Tennessee
      • Knoxville, Tennessee, United States, 37922
        • The Baptist Hospital of East Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University
      • Nashville, Tennessee, United States, 37205
        • The Advanced Neurosciences Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine - The Methodist College Multiple Sclerosis Center
      • Houston, Texas, United States, 77030
        • The University of Texas Houston
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Neurology Center of Fairfax, Ltd.
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington
      • Tacoma, Washington, United States, 95405
        • Neurology Associates of Tacoma

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

MS patients on interferon beta

Description

Inclusion Criteria:

  1. Patients (male or female) diagnosed with relapsing forms of MS.
  2. Currently being treated with the same b-IFN (in accordance with FDA approved dosing and schedules) for 12 to 48 months inclusive.
  3. All levels of disability
  4. Age 18-65 years inclusive
  5. Subjects must be willing to be followed for the 6-month study period.

Exclusion Criteria:

  1. Patients with prior b-IFN NAb test (whether positive or negative).
  2. Patients who are currently being treated or have been treated within 6 months prior to screening with combination therapy (b-IFN plus any other immunosuppressant/immunomodulatory) other than IV steroids (either pulse or for a relapse).
  3. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
  4. Any other reasons that, in the opinion of the Investigator, the subject is determined to be unsuitable for enrollment into this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
1
subjects who are NAb positive
2
Subjects who are antibody negative
3
subjects who are BAb positive

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Investigators

  • Study Director: Thorsten Eickenhorst, MD, Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Study Completion (Actual)

August 1, 2007

Study Registration Dates

First Submitted

February 8, 2006

First Submitted That Met QC Criteria

February 8, 2006

First Posted (Estimate)

February 9, 2006

Study Record Updates

Last Update Posted (Estimate)

December 24, 2007

Last Update Submitted That Met QC Criteria

December 20, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 008-05-AVX

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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