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

NCT ID: NCT00179478

Last Updated: 2017-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-02-28
• Study Completion Date: 2009-03-31

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.

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

interferon beta 1a 30 ug IM once weekly

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

interferon beta 1a 30 ug IM once weekly

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

R. Philip Kinkel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Revere P Kinkel, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

MS Treatment Center at Griffin Hospital

Derby, Connecticut, United States

Jaeb Center for Health Research

Tampa, Florida, United States

MS Center of Atlanta

Atlanta, Georgia, United States

Beta Research, Inc

Elk Grove, Illinois, United States

University of Iowa College of Medicine

Iowa City, Iowa, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Michigan State University

East Lansing, Michigan, United States

St. Louis University Health Sciences Center

St Louis, Missouri, United States

Jacobs Neurological Institute

Buffalo, New York, United States

University of Rochester

Rochester, New York, United States

Carolinas Medical Center - MS Center

Charlotte, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

The Neurology Group

Norristown, Pennsylvania, United States

Univeristy of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Allegheny Neurological Associates

Pittsburgh, Pennsylvania, United States

Univeristy of Texas Houston Health Science Center

Houston, Texas, United States

Virginia Commonwealth University/Medical College of Virginia

Richmond, Virginia, United States

Neurological Associates, Inc.

Richmond, Virginia, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Vancouver Hospital Health Sciences Centre

Vancouver, British Columbia, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Ottawa General Hospital

Ottawa, Ontario, Canada

University of Toronto - St. Michael's Hospital

Toronto, Ontario, Canada

Hospital Notre Dame

Montreal, Quebec, Canada

Montreal Neurological Institute

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 11006365 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16436649 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21987393 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25344370 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25741224 (View on PubMed)

Other Identifiers

C-850 Extension study

Identifier Type: OTHER

Identifier Source: secondary_id

2003P000086

Identifier Type: -

Identifier Source: org_study_id