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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00666263
• Date of registration: 23/04/2008
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor Neuropathy
• Scientific 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
• Date of first enrolment: August 2008
• Target sample size: 50
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00666263
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Canada, Denmark, Netherlands, Poland, United States

Contacts

• Name: Baxter BioScience Investigator
• Affiliation: Baxter Healthcare Corporation

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multifocal Motor Neuropathy

Intervention(s)

Biological: 0.25% human albumin solution (Placebo)

Biological: Immune Globulin Intravenous (human), 10%

Primary Outcome(s)

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

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

Mean Relative Change in Grip Strength in the More Affected Hand [Time Frame: 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)]

Grip Strength in the More Affected Hand [Time Frame: 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]

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 [Time Frame: 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)]

Rate of Temporally Associated Adverse Events (AEs) Per Infusion [Time Frame: 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)]

The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

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 [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

Secondary Outcome(s)

Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) [Time Frame: 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]

Overall Disability Sum Score [Time Frame: 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]

Rate of Related AEs Per Infusion [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

The Proportion of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Tolerability Concerns/AEs [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

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

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

Proportion of Participants That Were Accelerated Forward Into the Next Stabilization Phase (ie Switched to Open-Label IGIV, 10%) [Time Frame: During the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

Rate of Related SAEs Per Infusion [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

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 [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

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

Grip Strength in the Less Affected Hand [Time Frame: 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]

Mean Relative Change in Grip Strength in the Less Affected Hand [Time Frame: 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)]

Mean Relative Change in Participants' Assessment of Physical Functioning on a Visual Analog Scale (VAS) [Time Frame: 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)]

Patient Global Impression of Change [Time Frame: 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]

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

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

The Proportion of Infusions Associated With One or More AEs Related to the Study Product [Time Frame: Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)]

Mean Relative Change in Overall Disability Sum Score [Time Frame: 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)]

Overall Disability Sum Score - Standardized [Time Frame: 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]

Secondary ID(s)

160604

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/03/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00666263