Clinical trial NCT00288990: A Serologic Study to Correlate Beta-IFN NAb Titers to Beta-IFN Induced Biomarker Response in Patients With Multiple Sclerosis
Official title: Impact of Neutralizing Antibodies on Interferon Responsive Genes Highlights Biomarker Response.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: MS
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2006-02-09
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: MS patients on interferon beta

Brief 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)


Eligibility criteria: 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.

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