Trial Outcomes & Findings for Study of Efficacy and Safety of Privigen in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy (NCT NCT01184846)

NCT ID: NCT01184846

Last Updated: 2024-06-25

Results Overview

Percentage of responders based on the adjusted Inflammatory Neuropathy Cause and Treatment Scale (INCAT) score. Responders were defined as those subjects who: 1) demonstrated a "clinically meaningful improvement" between baseline and Week 25, or 2) who were discontinued from the study for any reason after the start of IgPro10 treatment but with "clinically meaningful improvement" at the last study visit. "Clinically meaningful improvement" was a decrease of at least 1 adjusted INCAT score point excluding an improvement of one point in the total score if this improvement was only due to a decrease in the upper limb score of 1 to 0.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 31 participants
• Primary outcome timeframe: 25 weeks
• Results posted on: 2024-06-25

Participant Flow

This multicenter study enrolled subjects at 13 participating study centers in 5 countries in Europe.

A total of 31 subjects were screened and 28 were eligible. * Intravenous immunoglobulin (IVIG)-untreated subjects: screening took place up to 3 weeks prior to the first IgPro10 infusion * IVIG-pretreated subjects: Screening took place at any time at or after the last dose of pre-study IVIG (up to 10 weeks prior to the first IgPro10 infusion)

Participant milestones

Measure	IgPro10 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Overall Study STARTED	28
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	IgPro10 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Overall Study Adverse Event	2
Overall Study Insufficient response	1

Baseline Characteristics

Study of Efficacy and Safety of Privigen in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy

Baseline characteristics by cohort

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Age, Continuous	58.7 years STANDARD_DEVIATION 14.34 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Previous IVIG treatment IVIG-pretreated subjects	13 participants n=5 Participants
Previous IVIG treatment IVIG-untreated subjects	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 25 weeks

Population: The full analysis set (FAS) includes all subjects who received at least one dose of IgPro10, regardless of whether or not the subject recorded an efficacy variable measurement. The valid cases set (VCS) consists of all FAS subjects without any major protocol deviation (ie, the subjects who participated in the study as intended).

Percentage of responders based on the adjusted Inflammatory Neuropathy Cause and Treatment Scale (INCAT) score.

Responders were defined as those subjects who: 1) demonstrated a "clinically meaningful improvement" between baseline and Week 25, or 2) who were discontinued from the study for any reason after the start of IgPro10 treatment but with "clinically meaningful improvement" at the last study visit.

"Clinically meaningful improvement" was a decrease of at least 1 adjusted INCAT score point excluding an improvement of one point in the total score if this improvement was only due to a decrease in the upper limb score of 1 to 0.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Responder Rate FAS (n = 28)	60.7 percentage of responders Interval 42.409 to 76.434	—
Responder Rate VCS (n = 22)	63.6 percentage of responders Interval 42.952 to 80.267	—

SECONDARY outcome

Timeframe: Up to 34 weeks

Population: The FAS includes all subjects who received at least one dose of IgPro10, regardless of whether or not the subject recorded an efficacy variable measurement. Analysed subgroups include all subjects and IVIG-pretreated and IVIG-untreated subjects from baseline to completion, and IVIG-pretreated subjects from last IVIG treatment to completion.

The change in INCAT score was determined at the completion visit compared to baseline and to the last measurement under the previous IVIG treatment using a non-parametric analysis to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis.

The INCAT disability score ranges from 0 to 10 and is the sum of arm and leg disability each rated between 0 and 5 (where arm = 0 indicates 'no upper limb problems' and arm = 5 indicates 'inability to use either arm for any purposeful movement', and leg = 0 indicates 'walking not affected', and leg = 5 indicates 'restricted to wheelchair, unable to stand and walk a few steps with help'). Thus, a higher INCAT disability score indicates greater disability. Negative values for change in INCAT score indicate improvement, with a more negative value indicating greater improvement compared with the value at baseline.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Change in Adjusted INCAT Score All subjects; n = 28	-1.3 score on a scale Interval -2.0 to -0.5	—
Change in Adjusted INCAT Score IVIG-pretreated; n = 13	-2.0 score on a scale Interval -2.5 to -1.0	—
Change in Adjusted INCAT Score IVIG-untreated; n = 15	-1.0 score on a scale Interval -2.0 to 0.0	—
Change in Adjusted INCAT Score IVIG-pretreated (last IVIG to completion); n = 13	-2.0 score on a scale Interval -2.5 to -1.0	—

SECONDARY outcome

Timeframe: Up to 34 weeks

Population: The FAS includes all subjects who received at least one dose of IgPro10, regardless of whether or not the subject recorded an efficacy variable measurement. Analysed subgroups include all subjects and IVIG-pretreated and IVIG-untreated subjects from baseline to completion, and IVIG-pretreated subjects from last IVIG treatment to completion.

Change in maximum grip strength of the dominant hand. A non-parametric analysis was used to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis. Positive values for change in maximum grip strength indicate improvement.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Change in Maximum Grip Strength All subjects; n = 28	9.0 kPa Interval -1.0 to 22.3	—
Change in Maximum Grip Strength IVIG-pretreated; n = 13	8.0 kPa Interval -5.0 to 25.0	—
Change in Maximum Grip Strength IVIG-untreated; n = 15	9.0 kPa Interval -6.0 to 35.0	—
Change in Maximum Grip Strength IVIG-pretreated (last IVIG to completion); n = 13	-1.5 kPa Interval -12.5 to 14.5	—

SECONDARY outcome

Timeframe: Up to 34 weeks

Population: The FAS includes all subjects who received at least one dose of IgPro10, regardless of whether or not the subject recorded an efficacy variable measurement. Analysed subgroups include all subjects and IVIG-pretreated and IVIG-untreated subjects from baseline to completion, and IVIG-pretreated subjects from last IVIG treatment to completion.

The change in MRC sum score was determined at the completion visit compared to baseline and to the last measurement under the previous IVIG treatment using a non-parametric analysis to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis.

The 80-point MRC sum score is the sum of scores for eight bilateral (left and right side) muscle groups, each rated between 0 (no visible contraction) to 5 (normal movement). 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	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Change in Medical Research Council Sum Scale (MRC) All subjects; n = 28	6.5 score on a scale Interval 4.0 to 9.5	—
Change in Medical Research Council Sum Scale (MRC) IVIG-pretreated; n = 13	6.0 score on a scale Interval 2.5 to 10.0	—
Change in Medical Research Council Sum Scale (MRC) IVIG-untreated; n = 15	7.0 score on a scale Interval 3.0 to 12.5	—
Change in Medical Research Council Sum Scale (MRC) IVIG-pretreated (last IVIG to completion); n = 13	1.0 score on a scale Interval -2.5 to 4.5	—

SECONDARY outcome

Timeframe: At baseline and at Weeks 7, 13 and 19 (levels determined immediately before and after IVIG infusion), and at completion visit (Week 25)

Population: The FAS includes all subjects who received at least one dose of IgPro10, regardless of whether or not the subject recorded an efficacy variable measurement.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion n=27 Participants IgG levels were determined after infusion with IgPro10.
Immunoglobulin G (IgG) Level At Week 7 (n = 26)	1750.0 mg/dL Standard Deviation 313.73	3228.8 mg/dL Standard Deviation 803.22
Immunoglobulin G (IgG) Level At baseline (n = 28 and 27, respectively)	1259.5 mg/dL Standard Deviation 377.47	2859.2 mg/dL Standard Deviation 846.83
Immunoglobulin G (IgG) Level At Week 13 (n = 25)	1733.2 mg/dL Standard Deviation 353.00	3496.7 mg/dL Standard Deviation 575.11
Immunoglobulin G (IgG) Level At Week 19 (n = 25 and 24, respectively)	1684.6 mg/dL Standard Deviation 306.62	3386.1 mg/dL Standard Deviation 567.05
Immunoglobulin G (IgG) Level At Completion (n = 0 and 28 respectively)	NA mg/dL Standard Deviation NA There was no IgPro10 infusion at the completion visit. Thus, the IgG level measured at the completion visit represents the IgG level 3 weeks after the last infusion (at week 19) or at early discontinuation.	1943.6 mg/dL Standard Deviation 465.85

SECONDARY outcome

Timeframe: For the duration of the study, up to 34 weeks

Population: The safety data set (SDS) comprised all subjects treated with the study drug.

Overall rate of AEs per infusion.

Outcome measures

Measure	IgPro10 n=259 Infusions 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Frequency of Adverse Events (AEs)	0.417 AE rate per infusion	—

SECONDARY outcome

Timeframe: For the duration of the study, up to 34 weeks

Population: The SDS comprised all subjects treated with the study drug.

The severity of each AE was to be graded by the investigator as follows:

• Mild: Symptoms were easily tolerated and there was no interference with daily activities.
• Moderate: Discomfort enough to cause some interference with daily activities.
• Severe: Incapacitating with inability to work or do usual activity.

Outcome measures

Measure	IgPro10 n=259 Infusions 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Severity of AEs Per Infusion Mild AE	0.266 AE rate per infusion	—
Severity of AEs Per Infusion Moderate AE	0.143 AE rate per infusion	—
Severity of AEs Per Infusion Severe AE	0.008 AE rate per infusion	—

SECONDARY outcome

Timeframe: 34 weeks

Population: The SDS comprised all subjects treated with the study drug.

The severity of each AE was to be graded by the investigator as follows:

• Mild: Symptoms were easily tolerated and there was no interference with daily activities.
• Moderate: Discomfort enough to cause some interference with daily activities.
• Severe: Incapacitating with inability to work or do usual activity.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Severity of AEs Per Subject Mild AE	67.9 percentage of subjects	—
Severity of AEs Per Subject Moderate AE	46.4 percentage of subjects	—
Severity of AEs Per Subject Severe AE	7.1 percentage of subjects	—

SECONDARY outcome

Timeframe: For the duration of the study, up to 34 weeks

Population: The SDS comprised all subjects treated with the study drug.

The causal relationship of an AE to the study drug was to be assessed and assigned by the investigator.

Outcome measures

Measure	IgPro10 n=259 Infusions 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Relatedness of AEs Per Infusion Not Related	0.201 AE rate per infusion	—
Relatedness of AEs Per Infusion Unlikely Related	0.027 AE rate per infusion	—
Relatedness of AEs Per Infusion Possibly Related	0.081 AE rate per infusion	—
Relatedness of AEs Per Infusion Probably Related	0.042 AE rate per infusion	—
Relatedness of AEs Per Infusion Related	0.066 AE rate per infusion	—

SECONDARY outcome

Timeframe: For the duration of the study, up to 34 weeks

Population: The SDS comprised all subjects treated with the study drug.

The causal relationship of an AE to the study drug was to be assessed and assigned by the investigator.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Relatedness of AEs Per Subject Not Related	60.7 percentage of subjects	—
Relatedness of AEs Per Subject Unlikely Related	14.3 percentage of subjects	—
Relatedness of AEs Per Subject Possibly Related	39.3 percentage of subjects	—
Relatedness of AEs Per Subject Probably Related	25.0 percentage of subjects	—
Relatedness of AEs Per Subject Related	25.0 percentage of subjects	—

SECONDARY outcome

Timeframe: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.

Population: The SDS comprised all subjects treated with the study drug.

Systolic and diastolic blood pressure (BP) were measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and standard deviation (SD) of these individual mean changes is reported.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Mean Change in Systolic and Diastolic Blood Pressure During Infusion Systolic BP mean value of mean change	1.03 mm Hg Standard Deviation 7.62	—
Mean Change in Systolic and Diastolic Blood Pressure During Infusion Diastolic BP mean value of mean change	0.99 mm Hg Standard Deviation 7.46	—

SECONDARY outcome

Timeframe: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.

Population: The SDS comprised all subjects treated with the study drug

Pulse rate was measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and SD of these individual mean changes is reported.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Mean Change in Pulse Rate During Infusion	-1.14 beats per minute Standard Deviation 3.58	—

SECONDARY outcome

Timeframe: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.

Population: The SDS comprised all subjects treated with the study drug.

Body temperature was measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and SD of these individual mean changes is reported.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Mean Change in Body Temperature During Infusion	0.06 °C Standard Deviation 0.17	—

SECONDARY outcome

Timeframe: At Day 1 (baseline) and at Completion Visit (Week 25 or early discontinuation)

Population: The SDS comprised all subjects treated with the study drug.

Number of subjects with changes from normal/ANCS values at baseline to ACS values at Completion Visit in routine laboratory parameters including hematology and serum chemistry analytes. Investigators flagged each laboratory value as normal, ANCS or ACS at each assessment timepoint.

Outcome measures

Measure	IgPro10 n=28 Participants 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.	IgPro10 - After Infusion IgG levels were determined after infusion with IgPro10.
Number of Subjects With Normal/Abnormal Not Clinically Significant (ANCS) Value at Baseline Changing to Abnormal Clinically Significant (ACS) Value at Completion Visit in Routine Laboratory Parameters.	4 participants	—

Adverse Events

IgPro10

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	IgPro10 n=28 participants at risk 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Blood and lymphatic system disorders Haemolysis	7.1% 2/28 • Number of events 2 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Infections and infestations Diverticulitis	3.6% 1/28 • Number of events 1 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Nervous system disorders Chronic inflammatory demyelinating polyradiculoneuropathy	3.6% 1/28 • Number of events 1 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.

Other adverse events

Measure	IgPro10 n=28 participants at risk 10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Blood and lymphatic system disorders Leukopenia	14.3% 4/28 • Number of events 4 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Gastrointestinal disorders Nausea	10.7% 3/28 • Number of events 3 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
General disorders Asthenia	14.3% 4/28 • Number of events 4 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
General disorders Influenza-like illness	7.1% 2/28 • Number of events 2 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Injury, poisoning and procedural complications Contusion	7.1% 2/28 • Number of events 2 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 2/28 • Number of events 3 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	21.4% 6/28 • Number of events 7 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Nervous system disorders Headache	32.1% 9/28 • Number of events 20 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 2/28 • Number of events 2 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Skin and subcutaneous tissue disorders Rash	7.1% 2/28 • Number of events 2 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.
Vascular disorders Hypertension	14.3% 4/28 • Number of events 6 • For the duration of the study, up to 34 weeks. Only AEs starting at or after the first study drug infusion are included. The safety data set (SDS) comprised all subjects treated with the study drug.

Additional Information

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