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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Vivaglobin

About this trial

This is an interventional treatment trial for Multifocal Motor Neuropathy (MMN)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

San Raffaele Hospital
Inselspital
Dept. Clinical Immunology, Oxford Radcliffe Hospitals

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vivaglobin

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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).

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.

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.

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.

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.

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.

Number of Patients With Local/Injection Site Reactions

All AEs arising from local/injection site reactions.

Number of Patients With Clinically Relevant Changes in Laboratory Parameters

Laboratory parameters included hematology, serum chemistry, and urinalysis parameters.

Number of Patients With Clinically Relevant Changes in Vital Signs

Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.

Full Information

NCT ID

NCT00701662

First Posted

June 18, 2008

Last Updated

June 2, 2013

Sponsor

CSL Behring

1. Study Identification

Unique Protocol Identification Number

NCT00701662

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Completed

Study Start Date

November 2007 (undefined)

Primary Completion Date

January 2009 (Actual)

Study Completion Date

January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CSL Behring

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multifocal Motor Neuropathy (MMN)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vivaglobin

Arm Type

Experimental

Arm Description

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).

Intervention Type

Biological

Intervention Name(s)

Vivaglobin

Other Intervention Name(s)

Human Normal Immunoglobulin

Primary Outcome Measure Information:

Title

Change From Baseline to Week 24 in Muscle Strength

Description

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.

Time Frame

Baseline to week 24

Title

Mean Overall MRC Score at Baseline and Week 24

Description

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.

Time Frame

Baseline and week 24

Secondary Outcome Measure Information:

Title

Change From Baseline to Week 24 in Disability

Description

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.

Time Frame

Baseline to week 24

Title

Mean Disability Score at Baseline and Week 24

Description

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.

Time Frame

Baseline and Week 24

Title

Change From Baseline to the Completion Visit in Motor Function

Description

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.

Time Frame

Baseline to the completion visit (up to week 25)

Title

Mean Motor Function Score at Screening and Week 25

Description

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).

Time Frame

Screening and week 25

Title

Health-Related Quality of Life at Baseline and Week 25

Description

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.

Time Frame

At baseline and week 25

Title

Treatment Satisfaction at Baseline and Week 25

Description

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.

Time Frame

At baseline and week 25

Title

Overall Health Status at Baseline and Week 25

Description

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.

Time Frame

Baseline and week 25

Title

Number of Patients With Adverse Events (AEs) by Severity and Relatedness

Description

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.

Time Frame

For the duration of the study, up to Week 25

Title

Rate of AEs by Severity and Relatedness

Description

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.

Time Frame

For the duration of the study, up to Week 25

Title

Number of Patients With Local/Injection Site Reactions

Description

All AEs arising from local/injection site reactions.

Time Frame

For the duration of the study, up to Week 25

Title

Number of Patients With Clinically Relevant Changes in Laboratory Parameters

Description

Laboratory parameters included hematology, serum chemistry, and urinalysis parameters.

Time Frame

Baseline to Week 25

Title

Number of Patients With Clinically Relevant Changes in Vital Signs

Description

Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.

Time Frame

Baseline to Week 25

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthias Sturzenegger, MD

Organizational Affiliation

Inselspital, University Hospital of Bern

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Bernd Kieseier, MD

Organizational Affiliation

Neurologische Klinik, Heinrich-Heine-University, Düsseldorf

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Giancarlo Comi, MD

Organizational Affiliation

San Raffaele Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Siraj Misbah, MD

Organizational Affiliation

Dept. Clinical Immunology, Oxford Radcliffe Hospitals

Official's Role

Principal Investigator

Facility Information:

Facility Name

San Raffaele Hospital

City

Milan

Country

Italy

Facility Name

Inselspital

City

Bern

Country

Switzerland

Facility Name

Dept. Clinical Immunology, Oxford Radcliffe Hospitals

City

Oxford

Country

United Kingdom

12. IPD Sharing Statement

Citations:

Citation

Misbah S, et al. Efficacy and safety of subcutaneous immunoglobulin, Vivaglobin, in patients with multifocal motor neuropathy. Journal of Neurology 257(Suppl 1):S105-S106, 2010.

Results Reference

result

PubMed Identifier

21692906

Citation

Misbah SA, Baumann A, Fazio R, Dacci P, Schmidt DS, Burton J, Sturzenegger M. A smooth transition protocol for patients with multifocal motor neuropathy going from intravenous to subcutaneous immunoglobulin therapy: an open-label proof-of-concept study. J Peripher Nerv Syst. 2011 Jun;16(2):92-7. doi: 10.1111/j.1529-8027.2011.00330.x.

Results Reference

result

Links:

URL

http://www.cslbehring.com/clinical-trials/contact-us.htm?registryRefNum=NCT00701662&registryName=ctgov

Description

Click here to request more information about this study

Multifocal Motor Neuropathy (MMN)

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial