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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00288990
• Other study ID #: 008-05-AVX
• Status: Completed
• Phase: Phase 4
• First received: February 8, 2006
• Last updated: December 20, 2007
• Start date: January 2006
• Est. completion date: August 2007

Study information

• Verified date: December 2007
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama - Birmingham	Birmingham	Alabama
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	The Multiple Sclerosis Center at the Ohio State University	Columbus	Ohio
United States	Physicians Resource Network	Cullman	Alabama
United States	Mercy Ruan Neurology Clinic	Des Moines	Iowa
United States	Neurology Center of Fairfax, Ltd.	Fairfax	Virginia
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Baylor College of Medicine - The Methodist College Multiple Sclerosis Center	Houston	Texas
United States	The University of Texas Houston	Houston	Texas
United States	University of California - Irvine	Irvine	California
United States	The Baptist Hospital of East Tennessee	Knoxville	Tennessee
United States	Kentucky Neuroscience Research / University Neurologists, P.S.C	Louisville	Kentucky
United States	The Advanced Neurosciences Institute	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	OSF Saint Francis Medical Center, Illinois Neurological Institute	Peoria	Illinois
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Brown University / Rhode Island Hospital	Providence	Rhode Island
United States	University of California San Francisco - MS Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	BJC Medical Group	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	Neurology Associates of Tacoma	Tacoma	Washington
United States	Tampa Neurology	Tampa	Florida
United States	Family Health Center	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States,