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

This study has been completed.
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00288990
First received: February 8, 2006
Last updated: December 20, 2007
Last verified: December 2007
  Purpose

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)


Condition Phase
Multiple Sclerosis
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Impact of Neutralizing Antibodies on Interferon Responsive Genes Highlights Biomarker Response.

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Biospecimen Retention:   Samples With DNA

whole blood and serum


Estimated Enrollment: 300
Study Start Date: January 2006
Study Completion Date: August 2007
Groups/Cohorts
1
subjects who are NAb positive
2
Subjects who are antibody negative
3
subjects who are BAb positive

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

MS patients on interferon beta

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288990

  Show 28 Study Locations
Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Thorsten Eickenhorst, MD Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec MD, Biogen Idec
ClinicalTrials.gov Identifier: NCT00288990     History of Changes
Other Study ID Numbers: 008-05-AVX
Study First Received: February 8, 2006
Last Updated: December 20, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen Idec:
MS

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 01, 2014