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

Baxalta now part of Shire50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Multifocal Motor Neuropathy

Interventions

Immune Globulin Intravenous (human), 10%BIOLOGICAL

Dose: Previous dose with 3, 4, or 6 cycles depending on previous schedule (patient specific)

0.25% human albumin solution (Placebo)BIOLOGICAL

Cross-over Period 1 (Randomized) / Cross-over Period 2 (opposite of the treatment received in Cross-over Period 1); Dose: Same volume/frequency as Stabilization Phase 1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (17)

Unnamed facility

Los Angeles, California, United States

Unnamed facility

Stanford, California, United States

Unnamed facility

Centennial, Colorado, United States

Outcomes

Primary Outcomes

Grip Strength in the More Affected Hand

The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. Each grip strength test consisted of 3 maximal repeated contractions (trials). Each participant will perform 2 sessions of grip strength testing. After a 10-minute break, the testing session will be repeated for a total of 6 grip repetitions per 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 More Affected Hand

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

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

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

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

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Data from ClinicalTrials.gov

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Secondary Outcomes

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

Relative grip strength change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

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 Less Affected Hand

Mean Relative Change in Grip Strength in the Less Affected Hand

Relative Change is defined as 100 \* (End of the Cross-Over Period - Baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

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%)

Participants were permitted to switch from blinded treatment with placebo or IGIV, 10% to open label IGIV, 10% if they and investigator agreed that deterioration had occurred to the extent that the participant had unacceptable difficulty carrying out daily activities involving the affected muscles, or decline in grip strength of ≥50% in the more affected hand had occurred.

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

Patient Global Impression of Change

Patient Global Impression of Change was measured on an ordinal scale of 1-7, higher scores representing greater perceived deterioration since the previous efficacy assessment (ranging from (1) very much improved to very much worse (7)). 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse

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

Overall Disability Sum Score

The overall disability sum scale (based on Merkies et al., 2002) is a patient questionnaire that measures disability. Overall disability sum score = arm disability scale (range 0-5) + leg disability scale (range 0-7); Overall Range: 0 (no signs of disability) to 12 (maximum disability).

Overall Disability Sum Score - Standardized

Mean Relative Change in Overall Disability Sum Score

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The overall disability sum scale (based on Merkies et al., 2002) is a patient questionnaire that measures disability (from 0, "no signs of disability" to 12, "most severe disability"). This was standardized to a scale of 0 to 100 (the best score being 100) to allow calculation of relative changes.

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)

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

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

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

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

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)

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

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their non-dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

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

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Participants picked up the pegs one at a time (nine in total), and put them into the holes on the board as quickly as possible, in any order until all the holes were filled. Then, without pausing, participants removed the pegs one at a time and returned them to the container as quickly as possible. Each participant did this two times with their non-dominant hand. The 9-HCT objective is to see how fast participants could put all of the pegs in and take them out again.

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)

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

The VAS measured patients' assessment of physical functioning on a 10 centimeter scale of 0-10, on which 0 represents "no symptoms" and 10 "disabled, unable to use affected limbs".

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

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The VAS measured patients' assessment of physical functioning on a 10 centimeter scale of 0-10, on which 0 represents "no symptoms" and 10 "disabled, unable to use affected limbs".

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)

Rate of Related AEs Per Infusion

The total number of AEs determined by the investigator to be related to the study product that occur at any time during the study divided by the total number of infusions, and multiplied by 100.

Time frame: Throughout 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

The total number of SAEs determined by the investigator to be related to the study product that occur at any time during the study divided by the total number of infusions, and multiplied by 100.

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)

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)

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)