Trial Outcomes & Findings for A Study of Purified Human Antibodies Administered Subcutaneously to Patients With Multifocal Motor Neuropathy (MMN) (NCT NCT00701662)

NCT ID: NCT00701662

Last Updated: 2013-08-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: Baseline to week 24
• Results posted on: 2013-08-01

Participant Flow

Participant milestones

Measure	Vivaglobin Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Overall Study STARTED	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Vivaglobin Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Overall Study Lack of Efficacy	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Age Continuous	57.3 years STANDARD_DEVIATION 8.78 • n=5 Participants
Age, Customized > 18 to < 65 years	5 participants n=5 Participants
Age, Customized >= 65 years	3 participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to week 24

Population: The Intention-to-Treat (ITT) data set comprised all patients treated with the study drug who had at least one post-baseline measurement for 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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Change From Baseline to Week 24 in Muscle Strength	0.4 score on a scale 95% Confidence Interval 5.07 • Interval -4.5 to 5.0

PRIMARY outcome

Timeframe: Baseline and week 24

Population: The ITT data set comprised all patients treated with the study drug who had at least one post-baseline measurement for muscle strength.

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Mean Overall MRC Score at Baseline and Week 24 MRC score at baseline (n = 8)	178.3 score on a scale Interval 149.0 to 197.0
Mean Overall MRC Score at Baseline and Week 24 MRC score at week 24 (n = 7)	184.3 score on a scale Interval 171.0 to 198.0

SECONDARY outcome

Timeframe: Baseline to week 24

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Change From Baseline to Week 24 in Disability	0.1 score on a scale 95% Confidence Interval 1.13 • Interval -1.0 to 1.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Mean Disability Score at Baseline and Week 24 Disability score at baseline (n = 8)	2.0 score on a scale Interval 1.0 to 3.0
Mean Disability Score at Baseline and Week 24 Disability score at week 24 (n = 7)	1.9 score on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: Baseline to the completion visit (up to week 25)

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Change From Baseline to the Completion Visit in Motor Function	0.4 score on a scale 95% Confidence Interval 1.94 • Interval -1.5 to 0.75

SECONDARY outcome

Timeframe: Screening and week 25

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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).

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Mean Motor Function Score at Screening and Week 25 Motor function score at screening (n = 8)	5.5 score on a scale Interval 0.0 to 8.0
Mean Motor Function Score at Screening and Week 25 Motor function score at week 25 (n = 7)	4.6 score on a scale Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: At baseline and week 25

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Health-Related Quality of Life at Baseline and Week 25 Current treatment, baseline (n = 8)	2.6 units on a scale Full Range 1.06 • Interval 1.0 to 4.0
Health-Related Quality of Life at Baseline and Week 25 Current treatment, week 25 (n = 7)	1.3 units on a scale Full Range 0.49 • Interval 1.0 to 2.0
Health-Related Quality of Life at Baseline and Week 25 At home, baseline (n = 3)	1.0 units on a scale Full Range 0.00 • Interval 1.0 to 1.0
Health-Related Quality of Life at Baseline and Week 25 At home, week 25 (n = 7)	1.1 units on a scale Full Range 0.38 • Interval 1.0 to 2.0
Health-Related Quality of Life at Baseline and Week 25 In the hospital/doctor's office, baseline (n = 7)	2.9 units on a scale Full Range 1.57 • Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: At baseline and week 25

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Treatment Satisfaction at Baseline and Week 25 Treatment interference, baseline (n = 8)	60.76 units on a scale Full Range 25.827 • Interval 8.3 to 97.2
Treatment Satisfaction at Baseline and Week 25 Treatment interference, week 25 (n = 6)	91.67 units on a scale Full Range 9.780 • Interval 75.0 to 100.0
Treatment Satisfaction at Baseline and Week 25 Therapy-related problems, baseline (n = 8)	70.30 units on a scale Full Range 27.055 • Interval 8.3 to 91.7
Treatment Satisfaction at Baseline and Week 25 Therapy-related problems, week 25 (n = 7)	89.29 units on a scale Full Range 14.402 • Interval 66.7 to 100.0
Treatment Satisfaction at Baseline and Week 25 Therapy setting, baseline (n = 8)	75.01 units on a scale Full Range 33.844 • Interval 5.6 to 100.0
Treatment Satisfaction at Baseline and Week 25 Therapy setting, week 25 (n = 6)	96.28 units on a scale Full Range 6.743 • Interval 83.3 to 100.0
Treatment Satisfaction at Baseline and Week 25 Treatment costs, baseline (n = 8)	70.84 units on a scale Full Range 34.498 • Interval 0.0 to 100.0
Treatment Satisfaction at Baseline and Week 25 Treatment costs, week 25 (n = 6)	86.10 units on a scale Full Range 19.486 • Interval 50.0 to 100.0

SECONDARY outcome

Timeframe: Baseline and week 25

Population: The analysis population comprised the subjects in the ITT data set (ie, all patients treated with the study drug) who had at least one post-baseline value (and if necessary a baseline value).

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Overall Health Status at Baseline and Week 25 Baseline (n = 8)	72.1 units on a scale Full Range 15.38 • Interval 52.0 to 96.0
Overall Health Status at Baseline and Week 25 Week 25 (n = 7)	73.9 units on a scale Full Range 14.67 • Interval 50.0 to 98.0

SECONDARY outcome

Timeframe: For the duration of the study, up to Week 25

Population: The safety data set (SDS) comprised all treated patients.

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.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Number of Patients With Adverse Events (AEs) by Severity and Relatedness All AEs	4 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Mild AEs	3 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Moderate AEs	2 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Severe AEs	0 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Not related AEs	4 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Possibly related AEs	0 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Probably related AEs	0 participants
Number of Patients With Adverse Events (AEs) by Severity and Relatedness Related AEs	1 participants

SECONDARY outcome

Timeframe: For the duration of the study, up to Week 25

Population: The SDS comprised all treated patients.

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.

Outcome measures

Measure	Vivaglobin n=183 Infusions Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Rate of AEs by Severity and Relatedness All AEs	0.104 AEs per infusion
Rate of AEs by Severity and Relatedness Mild AEs	0.093 AEs per infusion
Rate of AEs by Severity and Relatedness Moderate AEs	0.011 AEs per infusion
Rate of AEs by Severity and Relatedness Severe AEs	0.000 AEs per infusion
Rate of AEs by Severity and Relatedness Not related AEs	0.038 AEs per infusion
Rate of AEs by Severity and Relatedness Possibly related AEs	0.000 AEs per infusion
Rate of AEs by Severity and Relatedness Probably related AEs	0.000 AEs per infusion
Rate of AEs by Severity and Relatedness Related AEs	0.066 AEs per infusion

SECONDARY outcome

Timeframe: For the duration of the study, up to Week 25

Population: The SDS comprised all treated patients.

All AEs arising from local/injection site reactions.

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Number of Patients With Local/Injection Site Reactions Total	1 participants
Number of Patients With Local/Injection Site Reactions Injection site oedema	1 participants
Number of Patients With Local/Injection Site Reactions Injection site pruritis	1 participants
Number of Patients With Local/Injection Site Reactions Skin reaction	1 participants

SECONDARY outcome

Timeframe: Baseline to Week 25

Population: The SDS comprised all treated patients.

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

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Number of Patients With Clinically Relevant Changes in Laboratory Parameters	0 participants

SECONDARY outcome

Timeframe: Baseline to Week 25

Population: The SDS comprised all treated patients.

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

Outcome measures

Measure	Vivaglobin n=8 Participants Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Number of Patients With Clinically Relevant Changes in Vital Signs	0 participants

Adverse Events

Vivaglobin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vivaglobin n=8 participants at risk Human normal immunoglobulin, 0.1 to 0.5 g/kg body weight per week.
Blood and lymphatic system disorders Spontaneous haematoma	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
General disorders Asthenia	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
General disorders Injection-site oedema	12.5% 1/8 • Number of events 4 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
General disorders Injection-site pruritus	12.5% 1/8 • Number of events 4 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Infections and infestations Influenza	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Infections and infestations Orchitis	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Nervous system disorders Hemicephalalgia	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Nervous system disorders Multifocal motor neuropathy	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Skin and subcutaneous tissue disorders Erythema	12.5% 1/8 • Number of events 1 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.
Skin and subcutaneous tissue disorders Skin reaction	12.5% 1/8 • Number of events 4 • For the duration of the study, up to Week 25. The SDS comprised all treated patients. "General disorders" were collected under the Medical Dictionary for Regulatory Activities System organ class (MedDRA SOC) General disorders and administration site conditions.

Additional Information

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Results disclosure agreements

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