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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT00701662
First received: June 18, 2008
Last updated: June 2, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Multifocal Motor Neuropathy (MMN)
Biological: Vivaglobin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicentre Study of Subcutaneous Immunoglobulin (SCIG) in Patients With Multifocal Motor Neuropathy (MMN)

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in Muscle Strength [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]

    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.


  • Mean Overall MRC Score at Baseline and Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline to Week 24 in Disability [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]

    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.


  • Mean Disability Score at Baseline and Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to the Completion Visit in Motor Function [ Time Frame: Baseline to the completion visit (up to week 25) ] [ Designated as safety issue: No ]

    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.


  • Mean Motor Function Score at Screening and Week 25 [ Time Frame: Screening and week 25 ] [ Designated as safety issue: No ]
    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).

  • Health-Related Quality of Life at Baseline and Week 25 [ Time Frame: At baseline and week 25 ] [ Designated as safety issue: No ]

    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.


  • Treatment Satisfaction at Baseline and Week 25 [ Time Frame: At baseline and week 25 ] [ Designated as safety issue: No ]
    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.

  • Overall Health Status at Baseline and Week 25 [ Time Frame: Baseline and week 25 ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Adverse Events (AEs) by Severity and Relatedness [ Time Frame: For the duration of the study, up to Week 25 ] [ Designated as safety issue: Yes ]

    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.


  • Rate of AEs by Severity and Relatedness [ Time Frame: For the duration of the study, up to Week 25 ] [ Designated as safety issue: Yes ]

    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.


  • Number of Patients With Local/Injection Site Reactions [ Time Frame: For the duration of the study, up to Week 25 ] [ Designated as safety issue: Yes ]
    All AEs arising from local/injection site reactions.

  • Number of Patients With Clinically Relevant Changes in Laboratory Parameters [ Time Frame: Baseline to Week 25 ] [ Designated as safety issue: Yes ]
    Laboratory parameters included hematology, serum chemistry, and urinalysis parameters.

  • Number of Patients With Clinically Relevant Changes in Vital Signs [ Time Frame: Baseline to Week 25 ] [ Designated as safety issue: Yes ]
    Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.


Enrollment: 8
Study Start Date: November 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vivaglobin
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
Other Name: Human Normal Immunoglobulin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701662

Locations
Italy
San Raffaele Hospital
Milan, Italy
Switzerland
Inselspital
Bern, Switzerland
United Kingdom
Dept. Clinical Immunology, Oxford Radcliffe Hospitals
Oxford, United Kingdom
Sponsors and Collaborators
CSL Behring
Investigators
Principal Investigator: Matthias Sturzenegger, MD Inselspital, University Hospital of Bern
Principal Investigator: Bernd Kieseier, MD Neurologische Klinik, Heinrich-Heine-University, Düsseldorf
Principal Investigator: Giancarlo Comi, MD San Raffaele Hospital
Principal Investigator: Siraj Misbah, MD Dept. Clinical Immunology, Oxford Radcliffe Hospitals
  More Information

Additional Information:
Publications:
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT00701662     History of Changes
Other Study ID Numbers: 1464, ZLB06_006CR, 2007-000710-37
Study First Received: June 18, 2008
Results First Received: June 2, 2013
Last Updated: June 2, 2013
Health Authority: Switzerland: Swissmedic
Germany: Paul-Ehrlich-Institut
Italy: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Neuritis
Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Antibodies
Immunoglobulins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014