Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis (CHAMPIONS10)

Controlled High-risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS10)

The current study is a continuation of the 5 year extension study of the phase III CHAMPS study (see reference). This study was designed to determine if immediate initiation of therapy with Interferon Beta-1a (AVONEX) after a first attack of multiple sclerosis (MS) continues to delay the development of further attacks (CDMS) and the development of neurological disability over a 10 year period of observation. The initial 5 year extension study, called CHAMPIONS5, reported that immediate initiation of interferon Beta-1a (AVONEX) after a first attack of MS continued to delay the development of CDMS and lowered relapse rates compared to delayed initiation of disease modifying treatment (usually with AVONEX) either at the time of a second attack or at the end of the phase III study (24 months). The study was extended to 10 years to determine if these effects are sustained and result in less long term permanent disability.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Optic Neuritis; Transverse Myelitis; Acute Brainstem/Cerebellar Syndrome
• Intervention / Treatment: Drug: interferon beta 1a 30 ug IM once weekly

Detailed Description

The CHAMPS study determined that immediate initiation of interferon beta 1a therapy (AVONEX) immediately following a first clinical demyelinating event in high risk patients (i.e. those with at least 2 asymptomatic white matter lesions on cranial MR imaging > 3 mm in diameter or ovoid) delayed the development of clinical definite Multiple Sclerosis (CDMS)(as defined by a second, clinically verifiable attack involving another part of the central nervous system) over 2 years of observation and significantly decreased the development of new or enlarging white matter lesions on MRI over 18 months (see reference). The current study is a long term extension of a cohort of CHAMPS study site and participants. The three main aims of the study are as follows:

1. To determine the long term neurological outcome in patients treated with interferon beta 1a (AVONEX) from onset of a first clinical demyelinating event
2. To determine if immediate initiation of AVONEX therapy (the CHAMPS Avonex treatment group) confers long term benefits compared to delayed initiation of therapy (the CHAMPS placebo group) on the rate of development of CDMS, annualized relapse rates, the development of permanent disability and MR measures of disease activity and progression.
3. To determine predictors of long term disease activity and disability in patients following a first clinical demyelinating event

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Vancouver Hospital Health Sciences Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa General Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • University of Toronto - St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute
    • Montreal, Quebec, Canada, H2l 4M1
      • Hospital Notre Dame
• United States
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • MS Treatment Center at Griffin Hospital
  • Florida
    • Tampa, Florida, United States, 33647
      • Jaeb Center for Health Research
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Ms Center Of Atlanta
  • Illinois
    • Elk Grove, Illinois, United States, 60007
      • Beta Research, Inc
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa College of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Health Sciences Center
  • New York
    • Buffalo, New York, United States, 14203
      • Jacobs Neurological Institute
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center - MS Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19401
      • The Neurology Group
    • Philadelphia, Pennsylvania, United States, 19104
      • Univeristy of Pennsylvania Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Neurological Associates
  • Texas
    • Houston, Texas, United States, 77030
      • Univeristy of Texas Houston Health Science Center
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University/Medical College of Virginia
    • Richmond, Virginia, United States, 23230
      • Neurological Associates, Inc.
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previous participation in CHAMPS study
• Participation in a study site willing to participate in the CHAMPIONS10 extension study
• Willingness to enroll in the CHAMPIONS 10 extension
• Willingness to sign informed consent

Exclusion Criteria:

• Discovery of an alternative neurological disorder other than MS as a cause of initial neurological symptoms
• A severe systemic disease with likely mortality within 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Immediate Treatment Group; Initiation of treatment with Interferon Beta 1a IM once weekly immediately after onset of a first demyelinating syndrome in high risk individuals	Drug: interferon beta 1a 30 ug IM once weekly; Immediate treatment group refers to those patients who were randomized to the interferon beta 1a 30 ug IM once weekly treatment arm of the original, controlled phase III CHAMPS study; Delayed treatment group refers to those patients who were randomized to the placebo group during the original controlled, phase III CHAMPS study and did not start treatment, if at all, until they completed the CHAMPS study protocol at a later date.
ACTIVE_COMPARATOR: Delayed Treatment Group; Delayed initiation of of Interferon beta-1a IM once weekly at diagnosis of clinically definite MS, at conclusion of initial CHAMPS study or during long term observation	Drug: interferon beta 1a 30 ug IM once weekly; Immediate treatment group refers to those patients who were randomized to the interferon beta 1a 30 ug IM once weekly treatment arm of the original, controlled phase III CHAMPS study; Delayed treatment group refers to those patients who were randomized to the placebo group during the original controlled, phase III CHAMPS study and did not start treatment, if at all, until they completed the CHAMPS study protocol at a later date.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Development of Clinical Definite Multiple Sclerosis (CDMS) Over 10 Years	Percent cumulative probability of developing CDMS over 10 years . CDMS was defined as the development of new visual or neurological symptoms discrete from the patients initial event with objective findings on examination.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Relapse Rate	annualized # of relapses between years 0 and 10	10 years
Number of Participants With an EDSS > 3.5 at Study Completion	The EDSS is an ordinal scale of neurological impairment in Multiple Sclerosis with a range of 0 to 10 with 0.5 increments. A score of 0 is normal and 10 is death from MS. Scores from 1 to 3.5 are considered mild impairment , 4.0 to 6.5 is moderate and greater than 6.5 is severe impairment.	10 years
The Number of New or Enlarging MRI T2 Lesions at 10 Years	These are counts of new or significantly enlarged lesions over 10 years on brain MRI reflecting interval radiographic disease activity	10 years

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Biogen
• Investigators: Principal Investigator: Revere P Kinkel, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, Simonian NA, Slasor PJ, Sandrock AW. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000 Sep 28;343(13):898-904. doi: 10.1056/NEJM200009283431301.
• Kinkel RP, Kollman C, O'Connor P, Murray TJ, Simon J, Arnold D, Bakshi R, Weinstock-Gutman B, Brod S, Cooper J, Duquette P, Eggenberger E, Felton W, Fox R, Freedman M, Galetta S, Goodman A, Guarnaccia J, Hashimoto S, Horowitz S, Javerbaum J, Kasper L, Kaufman M, Kerson L, Mass M, Rammohan K, Reiss M, Rolak L, Rose J, Scott T, Selhorst J, Shin R, Smith C, Stuart W, Thurston S, Wall M; CHAMPIONS Study Group. IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology. 2006 Mar 14;66(5):678-84. doi: 10.1212/01.wnl.0000200778.65597.ae. Epub 2006 Jan 25.
• Kinkel RP, Dontchev M, Kollman C, Skaramagas TT, O'Connor PW, Simon JH; Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance Investigators. Association between immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome and long-term outcomes: a 10-year follow-up of the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance. Arch Neurol. 2012 Feb;69(2):183-90. doi: 10.1001/archneurol.2011.1426. Epub 2011 Oct 10.
• Simon JH, Kinkel RP, Kollman C, O'Connor P, Fisher E, You X, Hyde R; CHAMPIONS Investigators Group. Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS Multiple Sclerosis Prevention Trial. Mult Scler. 2015 Apr;21(4):415-22. doi: 10.1177/1352458514547407. Epub 2014 Oct 24.
• Kinkel RP, Laforet G, You X. Disease-related determinants of quality of life 10 years after clinically isolated syndrome. Int J MS Care. 2015 Jan-Feb;17(1):26-34. doi: 10.7224/1537-2073.2013-041.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (ESTIMATE): September 16, 2005

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2017
• Last Update Submitted That Met QC Criteria: August 6, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: MRI; Optic neuritis; Multiple sclerosis; Transverse Myelitis; Interferon Beta
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neoplasms by Site; Eye Diseases; Neuromuscular Diseases; Central Nervous System Infections; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Spinal Cord Diseases; Nervous System Neoplasms; Optic Nerve Diseases; Cranial Nerve Diseases; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Multiple Sclerosis; Sclerosis; Neuritis; Optic Neuritis; Myelitis; Myelitis, Transverse; Cerebellar Diseases; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta
• Other Study ID Numbers: 2003P000086; C-850 Extension study (OTHER: Biogen Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO