A Study of Purified Human Antibodies Administered Subcutaneously to Patients With Multifocal Motor Neuropathy (MMN)

Study Overview
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Brief Summary
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The objective of this study is to assess efficacy, safety, and convenience of purified human antibodies administered under the skin in the treatment of MMN patients.

Official Title
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A Multicentre Study of Subcutaneous Immunoglobulin (SCIG) in Patients With Multifocal Motor Neuropathy (MMN)

Conditions
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Multifocal Motor Neuropathy (MMN)

Intervention / Treatment
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* Biological: Vivaglobin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with documented clinical diagnosis and electrophysiological evidence of MMN Patients who have previously responded to intravenous immunoglobulin (IVIG) and have been on stable treatment with IVIG for at least 12 weeks prior to screening Patients treated with the equivalent of ≥0.4g/kg body weight (bw) IVIG per month Provision of informed consent by patient Exclusion Criteria: Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) concentration >2.5 times the upper normal limit (UNL) Creatinine concentration >1.5 times the UNL Known allergic reactions to blood products Any skin disease interfering with the assessment of injection site reactions Any other medical condition, which in the opinion of the investigator, might interfere with successful completion of the protocol Any condition likely to interfere with the evaluation of the study drug or satisfactory conduct of the trial Participation in a study with an investigational drug within three months prior to enrolment Patients treated with the equivalent of >2.0g/kg bw IVIG per month

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vivaglobin<br>Vivaglobin® is a 16% (160 mg/mL) liquid formulation of human normal immunoglobulin for subcutaneous infusion. Subjects will receive weekly infusions of Vivaglobin® at a weekly dosage calculated based on previous intravenous immunoglobulin treatment (between 0.1 to 0.5 g/kg body weight per week). | Biological: Vivaglobin<br> <br> * Other names: Human Normal Immunoglobulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Muscle Strength | The change in Medical Research Council (MRC) score was determined at week 24 compared to baseline using descriptive statistics and nonparametric, two-sided 95% confidence intervals based on the Hodges-Lehmann method. Data for one of the eight subjects was from week 13 as week 24 data were not available. The 200-point MRC sum score is the sum of scores for 20 bilateral (left and right side) muscle groups, each rated between 0 (no movement) to 5 (normal movement/power). A higher MRC sum score indicates greater muscle contraction/limb movement. Positive values for change in MRC sum score indicate improvement, with a more positive value indicating greater muscle contraction/ limb movement compared with the value at baseline. | Baseline to week 24 | 
| Mean Overall MRC Score at Baseline and Week 24 | The 200-point MRC sum score is the sum of scores for 20 bilateral (left and right side) muscle groups, each rated between 0 (no movement) to 5 (normal movement/power). A higher MRC sum score indicates greater muscle contraction/limb movement. | Baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Disability | The change in disability score was determined at week 24 compared to baseline using descriptive statistics and nonparametric two-sided 95% confidence intervals based on the Hodges-Lehmann method. Data for one of the eight subjects was from week 13 as week 24 data were not available. Disability was measured using a modified Guy's Neurological Disability Scale, which comprises subscales for upper and lower limb disability. Both subscales comprise 6 grades, numbered from 0 (no upper limb problem/walking is not affected) to 5 (unable to use either arm for any purposeful movements/usually uses a wheelchair indoors). The disability score is calculated as the sum of both subscales, resulting in a score ranging from 0 to 10. A higher disability score indicates greater disability. Negative values for change in disability score indicate improvement, with a more negative value indicating greater improvement compared with the value at baseline. | Baseline to week 24 | 
| Mean Disability Score at Baseline and Week 24 | Disability was measured using a modified Guy's Neurological Disability Scale, which comprises subscales for upper and lower limb disability. Both subscales comprise 6 grades, numbered from 0 (no upper limb problem/walking is not affected) to 5 (unable to use either arm for any purposeful movements/usually uses a wheelchair indoors). The disability score is calculated as the sum of both subscales, resulting in a score ranging from 0 to 10. A higher disability score indicates greater disability. | Baseline and Week 24 | 
| Change From Baseline to the Completion Visit in Motor Function | The change in motor function was determined at the completion visit compared to baseline using descriptive statistics and nonparametric two-sided 95% confidence intervals based on the Hodges-Lehmann method. For each patient, four specific tasks were defined according to his/her weakened muscle group. The patient had to grade each of the tasks on a 5-point scale ranging from 0 (normal function) to 4 (not possible). The overall motor function score was calculated as the sum of the 4 grades, resulting in a score ranging from 0 (optimal) to 16 (worst). The baseline motor function score was calculated as the mean of the patient's assessments at Screening and Week 1. Negative values for change in motor function score indicate improvement, with a more negative value indicating greater improvement compared with the value at baseline. | Baseline to the completion visit (up to week 25) | 
| Mean Motor Function Score at Screening and Week 25 | For each patient, four specific tasks were defined according to his/her weakened muscle group. The patient had to grade each of the tasks on a 5-point scale ranging from 0 (normal function) to 4 (not possible). The overall motor function score was calculated as the sum of the 4 grades, resulting in a score ranging from 0 (optimal) to 16 (worst). | Screening and week 25 | 
| Health-Related Quality of Life at Baseline and Week 25 | Assessed using a questionnaire on patients' satisfaction with current immunoglobulin G (IgG) treatment, treatment at home, and treatment at the hospital/doctor's office. The questions were answered by choosing a number between 1 (extremely good) and 7 (extremely bad). Note: No patients received IgG treatment at the hospital/doctor's office at Week 25. | At baseline and week 25 | 
| Treatment Satisfaction at Baseline and Week 25 | Treatment satisfaction was assessed using the Life Quality Index, which comprises 15 items rated on a 7-point scale (1 = worst rating, 7 = best rating) with a possible maximum score of 105. The highest score indicates the highest satisfaction with the impact of treatment on social factors. The 15 items were summarized to 4 scales: treatment interference, therapy-related problems, therapy setting, and treatment costs. The raw scores for these scales were transformed to a score ranging from 0 to 100, with 100 being the best score achievable. | At baseline and week 25 | 
| Overall Health Status at Baseline and Week 25 | Overall Health Status was assessed using a Visual Analogue Scale (VAS). Patients were asked to rate their overall health status by placing a mark on a 100 mm VAS, with 0 being the worst imaginable state and 100 being the best imaginable state. | Baseline and week 25 | 
| Number of Patients With Adverse Events (AEs) by Severity and Relatedness | Included all AEs that occurred during the entire study period. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. | For the duration of the study, up to Week 25 | 
| Rate of AEs by Severity and Relatedness | The rate was the number of AEs over the number of infusions administered. Included all AEs that occurred during the entire study period. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. | For the duration of the study, up to Week 25 | 
| Number of Patients With Local/Injection Site Reactions | All AEs arising from local/injection site reactions. | For the duration of the study, up to Week 25 | 
| Number of Patients With Clinically Relevant Changes in Laboratory Parameters | Laboratory parameters included hematology, serum chemistry, and urinalysis parameters. | Baseline to Week 25 | 
| Number of Patients With Clinically Relevant Changes in Vital Signs | Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature. | Baseline to Week 25 |