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

Baxalta

Status and phase: Completed; Phase 3

Conditions: Multifocal Motor Neuropathy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00666263

160604

2009-013841-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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50 participants in 2 patient groups

IGIV, 10% Then Placebo

Experimental group

Description:

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).

Treatment:

Biological: 0.25% human albumin solution (Placebo)

Biological: Immune Globulin Intravenous (human), 10%

Placebo Then IGIV, 10%

Experimental group

Description:

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)

Treatment:

Biological: 0.25% human albumin solution (Placebo)

Biological: Immune Globulin Intravenous (human), 10%