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

NCT00179478 | Completed Phase 4 Results DMC

• 2 other identifiers: 2003P000086C-850 Extension study
• Study Type: interventional
• Target: 155
• Locations: 2 countries
• Sites: 26

Brief Summary

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.

Conditions

Multiple Sclerosis; Optic Neuritis; Transverse Myelitis; Acute Brainstem/Cerebellar Syndrome

Keywords

Multiple sclerosis; Interferon Beta; MRI; Optic neuritis; Transverse Myelitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Annualized Relapse Rate

  10 years

• Number of Participants With an EDSS > 3.5 at Study Completion

  10 years

• The Number of New or Enlarging MRI T2 Lesions at 10 Years

  10 years

Study Arms (2)

Immediate Treatment Group

EXPERIMENTAL

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

Delayed Treatment Group

ACTIVE COMPARATOR

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

Interventions

interferon beta 1a 30 ug IM once weekly DRUG

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.

Delayed Treatment Group; Immediate Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Biogen: collaborator

Study Sites (26)

MS Treatment Center at Griffin Hospital

Derby, Connecticut, 06418, United States

Location

Jaeb Center for Health Research

Tampa, Florida, 33647, United States

Location

MS Center of Atlanta

Atlanta, Georgia, 30327, United States

Location

Beta Research, Inc

Elk Grove, Illinois, 60007, United States

Location

University of Iowa College of Medicine

Iowa City, Iowa, 52242, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

St. Louis University Health Sciences Center

St Louis, Missouri, 63110, United States

Location

Jacobs Neurological Institute

Buffalo, New York, 14203, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Carolinas Medical Center - MS Center

Charlotte, North Carolina, 28207, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

The Neurology Group

Norristown, Pennsylvania, 19401, United States

Location

Univeristy of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny Neurological Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

Univeristy of Texas Houston Health Science Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University/Medical College of Virginia

Richmond, Virginia, 23219, United States

Location

Neurological Associates, Inc.

Richmond, Virginia, 23230, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Vancouver Hospital Health Sciences Centre

Vancouver, British Columbia, V6T 2B5, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Ottawa General Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

University of Toronto - St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Hospital Notre Dame

Montreal, Quebec, H2l 4M1, Canada

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

Related Publications (5)

• 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.

  PMID: 11006365 BACKGROUND

• 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.

  PMID: 16436649 BACKGROUND

• 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.

  PMID: 21987393 BACKGROUND

• 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.

  PMID: 25344370 BACKGROUND

• 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.

  PMID: 25741224 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Optic Neuritis; Myelitis, Transverse; Cerebellar Diseases

Interventions

Interferon beta-1a

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Myelitis; Central Nervous System Infections; Infections; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Central Nervous System Diseases; Spinal Cord Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases; Brain Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

selective attrition of patients with greater levels of disease activity may have occurred in this long term extension study

Results Point of Contact

• Title: Revere P Kinkel MD (PI)
• Organization: University of California San Diego

rkinkel@ucsd.edu

619-543-5295

Study Officials

• Revere P Kinkel, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open label study: The outcome committee determined the primary outcome event (the development of Clinically definite MS) without knowledge of original treatment assignment and the central MRI reading center was not aware of original treatment assignments
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: February 1, 2001
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: September 6, 2017
• Results First Posted: September 6, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); CA (6)