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

Study Overview
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Brief Summary
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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
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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: To determine the long term neurological outcome in patients treated with interferon beta 1a (AVONEX) from onset of a first clinical demyelinating event 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. To determine predictors of long term disease activity and disability in patients following a first clinical demyelinating event

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

Conditions
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Multiple Sclerosis, Optic Neuritis, Transverse Myelitis, Acute Brainstem/Cerebellar Syndrome

Intervention / Treatment
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* Drug: interferon beta 1a 30 ug IM once weekly


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Treatment Group<br>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<br>* 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.<br>|
| Active Comparator: Delayed Treatment Group<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Multiple sclerosis, Interferon Beta, Optic neuritis, Transverse Myelitis