Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor Neuropathy

Condition(s) targeted: Multifocal Motor Neuropathy

Intervention: Immune Globulin Intravenous (human), 10% (Biological); 0.25% human albumin solution (Placebo) (Biological)

Phase: Phase 3

Status: Completed

Sponsored by: Baxalta US Inc.

Official(s) and/or principal investigator(s):
Baxter BioScience Investigator, Study Director, Affiliation: Baxter Healthcare Corporation

The purpose of the study is to evaluate the efficacy (effect on grip strength and disability) and safety/tolerability of IGIV, 10% in subjects with Multifocal Motor Neuropathy.

Official title: A Randomized, Double-Blind, Placebo Controlled, Cross-over Study of the Effectiveness of Immune Globulin Intravenous (Human), 10% (IGIV, 10%) for the Treatment of Multifocal Motor Neuropathy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Grip Strength in the More Affected Hand

Mean Relative Change in Grip Strength in the More Affected Hand

Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs

Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS)

Rate of Temporally Associated Adverse Events (AEs) Per Infusion

The Percentage of Participants for Whom the Infusion Rate of Any Infusion Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason

The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason

The Percentage of Participants Reporting One or More Moderate or Severe AEs That Began During Infusion or Within 72 Hours of Completion of an Infusion

Secondary outcome:

Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer)

Grip Strength in the Less Affected Hand

Mean Relative Change in Grip Strength in the Less Affected Hand

Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)

Patient Global Impression of Change

Overall Disability Sum Score

Overall Disability Sum Score - Standardized

Mean Relative Change in Overall Disability Sum Score

Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand

Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand

Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)

Rate of Related AEs Per Infusion

Rate of Related SAEs Per Infusion

The Proportion of Participants for Whom the Infusion Rate of Any Infusion Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs

The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs

The Proportion of Infusions Associated With One or More AEs Related to the Study Product

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Written informed consent obtained from the participant prior to any study-related

procedures and study product administration

- Diagnosis of definite or probable MMN based on the criteria of the American

Association of Electrodiagnostic Medicine (AAEM) (Olney et al., 2003, see Section 15. 1 for the full length publication). Conduction block can be identified by a drop in amplitude. Diagnosis can be based on chart records a) Hand grip (finger flexor) weakness of Medical Research Council (MRC) grade 4 or less at disease onset or appearing prior to screening; b) No upper motor signs c) No bulbar or cranial signs or symptoms; d) No clinically identifiable sensory abnormalities

- Must be on a stable regimen of IGIV for at least 3 months prior to first study

product administration

- Treatment interval with IGIV of 2 to 5 weeks (+/- 3 days)

- Dose of IGIV to be 0. 4 to 2. 0 g per kg BW and infusion cycle

- Participants are adults, male or female, at least 18 years of age

- If female and capable of bearing children - have a negative urine pregnancy test

result at enrollment and agree to employ adequate birth control measures for the duration of the study

- Ability and willingness to travel to the study site for infusions and assessments if

required by the protocol Exclusion Criteria:

- Any clinical or electrophysiological evidence of coexisting neuropathy which may

interfere with outcome assessments, such as diabetic neuropathy, toxic neuropathy, or neuropathy due to systemic lupus erythematosus

- Treatment with other immunosuppressive agents besides IGIV, which has demonstrated

efficacy in MMN such as cyclophosphamide during the 3 months prior to enrollment (or treatment with Rituximab during the 12 months prior to enrollment). Pre-study treatment with mycophenolate mofetil or azathioprine is permitted if the dose has been stable for 3 months prior to enrollment.

- Cerebrospinal fluid protein > 100 mg/dL (if done as part of a previous evaluation)

- Participants positive at enrollment for one or more of the following: Hepatitis B

surface antigen (HBsAg), polymerase chain reaction (PCR) for Hepatitis C (HCV), PCR for human immunodeficiency virus (HIV) Type 1

- Participants with levels of alanine aminotransferase (ALT) or aspartate

aminotransferase (AST) > 2. 5 times the upper limit of normal for the testing laboratory

- Participants with neutropenia (defined as an absolute neutrophil count

[ANC]≤1000/mm^3)

- Participants with serum creatinine levels greater than 1. 5 times the upper limit of

normal for age and gender

- Participants with malignancy other than adequately treated basal cell or squamous

cell carcinoma of the skin or carcinoma in situ of the cervix

- Participants with a history of thrombotic episodes (deep vein thrombosis, myocardial

infarction, cerebrovascular accident)

- Participants who received any blood or blood product exposure other than an IGIV,

subcutaneous immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to enrollment

- Participants with an ongoing history of hypersensitivity or persistent reactions

(urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV or human albumin

- Participants with immunoglobulin A (IgA) deficiency and known anti IgA antibodies

- Participants using another investigational product or device within 30 days prior to

enrollment

- Participants who are unable or unwilling to meet all the requirements of this study

- If female, is pregnant or lactating at time of enrollment

Aarhus, Denmark

Calgary, Alberta, Canada

Los Angeles, California, United States

Stanford, California, United States

Centennial, Colorado, United States

Miami, Florida, United States

Kansas City, Kansas, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

St. Louis, Missouri, United States

Columbus, Ohio, United States

Kingston, Ontario, Canada

London, Ontario, Canada

Portland, Oregon, United States

Montreal, Quebec, Canada

Houston, Texas, United States

Seattle, Washington, United States

Related publications:

Merkies IS, Schmitz PI, van der Meché FG, Samijn JP, van Doorn PA; Inflammatory Neuropathy Cause and Treatment (INCAT) group. Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies. J Neurol Neurosurg Psychiatry. 2002 May;72(5):596-601.

Sharrack B, Hughes RA. The Guy's Neurological Disability Scale (GNDS): a new disability measure for multiple sclerosis. Mult Scler. 1999 Aug;5(4):223-33.

Starting date: August 2008
Last updated: June 26, 2015