Safety and Efficacy of Avonex in Subjects With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Phase 2

Completed

• Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy

• Registration Number: NCT00099489
• Lead Sponsor: Biogen

Brief Summary

The purpose of this study is to determine whether AVONEX (Interferon Beta-1a), when compared to placebo, reduces the total dose of IVIg that is administered after Visit 5 and through Visit 9 (Week 32, End of Study).

Detailed Description

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is an acquired peripheral neuropathy of unknown origin. The etiology is not well understood but is presumed to be immunological. Evidence for this comes from observed similarities to Guillain-Barre syndrome and from the favorable response with immunomodulatory treatments.

CIDP is a peripheral nervous system demyelinating neuropathy that is sometimes a corollary disorder to the central nervous system demyelination of multiple sclerosis (MS. The precise mechanisms underlying the pathogenesis are uncertain, but a number of those mechanisms support a potential role for immunomodulatory treatments such as interferon beta (e.g., Biogen Idec Inc.'s AVONEX).

The rationale for the use of AVONEX in CIDP derives from observations on the pathogenesis of the condition and its similarities to MS, the mechanism of action of AVONEX, clinical trials that have been performed in CIDP that support a role for IFN-beta, and the unmet need that currently exists because of availability and safety issues with existing therapies.

This Phase 2b study is a dose-ranging study designed to provide scientific evidence regarding the safety and efficacy of AVONEX in CIDP. In addition, the study aims to demonstrate the responsiveness and clinical relevance of changes in the MRC sum score and ODSS in CIDP patients.

Study Timeline

• Study Start: 2004-02
• Study First Submitted: 2004-12-15
• Study First Submitted QC: 2004-12-15
• Study First Posted: 2004-12-16
• Primary Completion: 2006-02
• Study Completion: 2006-02
• Status Verified: 2010-03
• Last Update Submitted: 2010-03-04
• Last Update Posted: 2010-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

Inclusion Criteria

• Written informed consent prior to any testing under this protocol
• Must be between 18 and 75 years of age
• Have a diagnosis of CIDP as determined by a board-certified or board-eligible neurologist, or equivalent, for at least 6 months, including fulfilling modified INCAT neurophysiological criteria for CIDP,CIDP motor deficit responsive to IVIg and alternative EP data that justifies subject inclusion, and/or supportive pathologic or laboratory data that supports the diagnosis of CIDP
• Documentation in the medical record prior to screening that the CIDP had been associated with loss of muscle strength, such that the MRC sum score was less than or equal to 58.
• Documentation in the medical record that the patient benefited fom IVIg treatment (patient had a 2-point change or equivalent in 60-point MRC sum score)
• Tested for IgM monoclonal gammopathy and found to have tested negative for IgM monoclonal gammopathy or if positive for IgM monoclonal gammopathy, then are MAG antibody-negative and proven to be IVI g responsive per protocol.
• Must have been clinically stable while on a constant regimen of IVIg (every 2-weeks, 3-weeks, 4-weeks or 5-weeks) in the 3 months prior to screening.

Exclusion Criteria*:

• Associated systemic disorder that might cause neuropathy.

• History of, or abnormal laboratory results indicative of any significant major disease or known drug hypersensitivity that, in the opinion of the investigator, would preclude the administration if IFN-beta or participation in this study.

• Subjects with diabetes mellitus will not be eligible, unless they satisfy both of the following requirements: a) their diabetes is well-controlled, with no retinopathy or nephropathy, having been identified during the ongoing care of their diabetes; and b) they have a normal sensory nerve action potential (SNAP) amplitude recorded in the sural nerve on at least one side of the body identified during electrophysiology (EP) testing documented in their medical record.

• Abnormal screening or baseline blood tests that the investigator deems clinically significant

• History of a seizure disorder prior to baseline (Visit 1, Week 0).

• History of suicidal ideation within 3 months prior to Baseline Visit (Week 0) or an episode of severe depression within 3 months prior to Baseline Visit (Week 0).

• Pure motor syndrome fulfilling criteria for multifocal motor neuropathy with conduction block.

• Pure sensory CIDP, or any other variant of CIDP without motor involvement

• Serious local infection or systemic infection within the 6 months prior to Screening.

• Use of IFN-beta at any time, use of plasma exchange, plasmapheresis, or any other immunosuppressant (with the exception of oral or non-systemic corticosteroids) within 6 months prior to Screening.

• History of intolerance to acetaminophen (paracetamol), ibuprofen, naproxen, and/or aspirin that would preclude use of at least one of these during the study.

• For female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as defined by the Investigator, during the study.

• Female subjects considering becoming pregnant while in the study

• Female subjects who are currently pregnant or breast-feeding.

  • This list is not exhaustive and there may be additional exclusions

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary endpoint for the efficacy analyses is the total IVIg dose (g/Kg) administered after Visit 5 and through Visit 9 (Week 32, End of Study).

Secondary Outcome Measures

Name	Time	Method
The time to disease progression.
Percentage reduction in IVIg dose (g/Kg).
The number of days between Visit 5 and either disease progression or Visit 9
(Week 32, End of Study).
The proportion of subjects with disease progression at Visit 9 (Week 32, End of Study).
The change in MRC sum score from baseline to the time of IVIg withdrawal.
Change from baseline to Visit 5 and to Visit 9 (Week 32, End of Study) in a composite score of maximal conduction velocity.

Trial Locations

Locations (20)

Phoenix Neurological Associates, Ltd.; 🇺🇸 Phoenix, Arizona, United States

Guy's Hospital/Dept. of Neuroimmunology; 🇬🇧 London, United Kingdom

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

University of Florida, Jacksonville; 🇺🇸 Jacksonville, Florida, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

London Health Sciences Center; 🇨🇦 London, Ontario, Canada

Raleigh Neurology Associates; 🇺🇸 Raleigh, North Carolina, United States

Neuromuscular Research Center; 🇺🇸 Scottsdale, Arizona, United States

Weill Medical College of Cornell University; 🇺🇸 New York, New York, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Harvard University/MGH; 🇺🇸 Boston, Massachusetts, United States

Tufts University/ St. Elizabeths; 🇺🇸 Boston, Massachusetts, United States

Montreal Neurological Hospital; 🇨🇦 Montreal, Quebec, Canada

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Institute of Clinical Neurosciences; 🇦🇺 Sydney, New South Wales, Australia

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

Louisiana State University; 🇺🇸 New Orleans, Louisiana, United States

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

St. Vincent's Hospital; 🇦🇺 Fitzroy, Victoria, Australia