Clinical trial NCT00666263: Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multifocal Motor Neuropathy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Grip Strength in the More Affected Hand
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Grip Strength in the More Affected Hand
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS)
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Rate of Temporally Associated Adverse Events (AEs) Per Infusion
timeFrame: Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: 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
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: 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
timeFrame: Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
Secondary outcomes:
measure: Percentage of Participants With at Least a 30% Decline in Relative Grip Strength in the More Affected Hand (Measured Using a DynEx Digital Dynamometer)
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Grip Strength in the Less Affected Hand
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Grip Strength in the Less Affected Hand
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%)
timeFrame: During the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: Patient Global Impression of Change
timeFrame: Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Overall Disability Sum Score
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Overall Disability Sum Score - Standardized
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Overall Disability Sum Score
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Dominant Hand
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Time Required by Participants to Complete the 9 Hole Peg Board Test (9-HPT) With the Non-Dominant Hand
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)
timeFrame: Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit
measure: Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS)
timeFrame: Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)
measure: Rate of Related AEs Per Infusion
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: Rate of Related SAEs Per Infusion
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: 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
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
measure: The Proportion of Infusions Associated With One or More AEs Related to the Study Product
timeFrame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Stanford
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Kansas City
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Calgary
country: Canada
state: Alberta
city: Kingston
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Aarhus
country: Denmark
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Merkies IS, Schmitz PI, van der Meche 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. doi: 10.1136/jnnp.72.5.596.
citation: 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. doi: 10.1177/135245859900500406.
citation: Koski CL, Schiff RI, Oh M, Lee D. Characteristics of patients with multifocal motor neuropathy enrolled in a randomized controlled trial of intravenous gammaglobulin. Poster. 63rd Annual Meeting of American Academy of Neurology (AAN), April 9-16, 2011, Honolulu, HI, USA.