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

NCT00666263 | Completed Phase 3 Results DMC

• 2 other identifiers: 1606042009-013841-27
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 17

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.

Conditions

Multifocal Motor Neuropathy

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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

• 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.

  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 Temporally Associated Adverse Events (AEs) Per Infusion

  The total number of all AEs which begin during or within 72 hours of completion of an infusion, irrespective of being related or not related to the study product (IGIV, 10% or Placebo), divided by the total number of infusions, and multiplied by 100.

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

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

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

  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 (19)

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

  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

  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

  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%)

  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

  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

Study Arms (2)

IGIV, 10% Then Placebo

EXPERIMENTAL

STUDY PART 1: Open-label stabilization on IGIV, 10% (Stabilization Phase 1) all participants. STUDY PART 2: IGIV, 10% (double-blind treatment Cross-Over Period 1). STUDY PART 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2). STUDY PART 4: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 2). STUDY PART 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3). Each study part was 12 weeks in length. Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg body weight (BW) per infusion cycle).

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

Placebo Then IGIV, 10%

EXPERIMENTAL

STUDY PART 1: Open-label stabilization on IGIV, 10% (Stabilization Phase 1) all participants. STUDY PART 2: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human) (Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment Cross-Over Period 1). STUDY PART 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2). STUDY PART 4: IGIV, 10% (double-blind treatment cross-over period 2). STUDY PART 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3). Each study part was 12 weeks in length. Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg BW per infusion cycle)

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

Interventions

Immune Globulin Intravenous (human), 10% BIOLOGICAL

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

Also known as: IGIV, 10%, GAMMAGARD LIQUID, KIOVIG

IGIV, 10% Then Placebo; Placebo Then IGIV, 10%

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

Also known as: BUMINATE 25%, Albumin (Human) Solution, Human Albumin 200 g/L Baxter

IGIV, 10% Then Placebo; Placebo Then IGIV, 10%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (17)

Unknown Facility

Los Angeles, California, United States

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Stanford, California, United States

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Centennial, Colorado, United States

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Miami, Florida, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Calgary, Alberta, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Montreal, Quebec, Canada

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Aarhus, Denmark

Location

Related Publications (3)

• 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.

  PMID: 11971045 BACKGROUND

• 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.

  PMID: 10467380 BACKGROUND

• 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.

  RESULT

MeSH Terms

Interventions

gamma-Globulins; Albumins; Solutions; Serum Albumin, Human

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations; Serum Albumin

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2008
• First Posted: April 24, 2008
• Study Start: August 22, 2008
• Primary Completion: August 11, 2011
• Study Completion: August 11, 2011
• Last Updated: May 19, 2021
• Results First Posted: March 13, 2013

Record last verified: 2021-04

Locations

DK (1); US (12); CA (4)