Trial Outcomes & Findings for Immune Globulin Intravenous (IGIV) For Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (NCT NCT00220740)

NCT ID: NCT00220740

Last Updated: 2016-03-23

Results Overview

The primary efficacy objective was the comparison of IGIV-C and Placebo group Responder rates. An Efficacy Period Responder was defined as a subject with ≥ 1 point improvement in the adjusted Inflammatory Neuropathy Case And Treatment (INCAT) score, with the improvement maintained through the end of Week 24 in the Efficacy Period. Measurements are reported in INCAT scale of 0-5 in both lower and upper extremities, for a total score of 0 to 10. INCAT scores for arm disability: 0 = no upper limb problems; 5 = inability to use either arm for any purposeful movement. INCAT scores for leg disability: 0= walking not affected; 5 = restricted to wheelchair, unable to stand and walk a few steps with help

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

117 participants

Primary outcome timeframe

6 months

Results posted on

2016-03-23

Participant Flow

The study was conducted at 31 study centers in USA, Poland, Argentina, Czech Republic, Canada, Mexico, Italy, Israel, Germany, and Serbia.

Participant milestones

Participant milestones
Measure
IGIV-C
2 g/kg loading dose, followed by 1 g/kg maintenance dose
Placebo
.1% albumin; 2g/kg loading dose and 1 g/kg maintenance dose
Efficacy Period
STARTED
59
58
Efficacy Period
COMPLETED
33
12
Efficacy Period
NOT COMPLETED
26
46
Rescue Treatment
STARTED
45
23
Rescue Treatment
COMPLETED
26
5
Rescue Treatment
NOT COMPLETED
19
18
Withdrawal Period
STARTED
43
31
Withdrawal Period
COMPLETED
37
16
Withdrawal Period
NOT COMPLETED
6
15

Reasons for withdrawal

Reasons for withdrawal
Measure
IGIV-C
2 g/kg loading dose, followed by 1 g/kg maintenance dose
Placebo
.1% albumin; 2g/kg loading dose and 1 g/kg maintenance dose
Efficacy Period
Entered rescue treatment with placebo
23
0
Efficacy Period
Adverse Event
1
1
Efficacy Period
Withdrawal by Subject
1
0
Efficacy Period
Protocol Violation
1
0
Efficacy Period
Entered Rescue Treatment with IGIV-C
0
45

Baseline Characteristics

Immune Globulin Intravenous (IGIV) For Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
IGIV-C
n=59 Participants
2 g/kg loading dose, followed by 1 g/kg maintenance dose
Placebo
n=58 Participants
.1% albumin, 2 g/kg loading dose, followed by 1 g/kg maintenance dose
Total
n=117 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
44 Participants
n=5 Participants
40 Participants
n=7 Participants
84 Participants
n=5 Participants
Age, Categorical
>=65 years
15 Participants
n=5 Participants
17 Participants
n=7 Participants
32 Participants
n=5 Participants
Age, Continuous
49.9 years
STANDARD_DEVIATION 17.31 • n=5 Participants
53.3 years
STANDARD_DEVIATION 15.63 • n=7 Participants
51.6 years
STANDARD_DEVIATION 16.51 • n=5 Participants
Sex: Female, Male
Female
28 Participants
n=5 Participants
12 Participants
n=7 Participants
40 Participants
n=5 Participants
Sex: Female, Male
Male
31 Participants
n=5 Participants
46 Participants
n=7 Participants
77 Participants
n=5 Participants
Region of Enrollment
United States
4 participants
n=5 Participants
2 participants
n=7 Participants
6 participants
n=5 Participants
Region of Enrollment
Czech Republic
7 participants
n=5 Participants
6 participants
n=7 Participants
13 participants
n=5 Participants
Region of Enrollment
Mexico
3 participants
n=5 Participants
5 participants
n=7 Participants
8 participants
n=5 Participants
Region of Enrollment
Canada
1 participants
n=5 Participants
1 participants
n=7 Participants
2 participants
n=5 Participants
Region of Enrollment
Argentina
8 participants
n=5 Participants
7 participants
n=7 Participants
15 participants
n=5 Participants
Region of Enrollment
Poland
15 participants
n=5 Participants
15 participants
n=7 Participants
30 participants
n=5 Participants
Region of Enrollment
Israel
8 participants
n=5 Participants
7 participants
n=7 Participants
15 participants
n=5 Participants
Region of Enrollment
Germany
2 participants
n=5 Participants
3 participants
n=7 Participants
5 participants
n=5 Participants
Region of Enrollment
Italy
6 participants
n=5 Participants
6 participants
n=7 Participants
12 participants
n=5 Participants
Region of Enrollment
Macedonia, The Former Yugoslav Republic of
5 participants
n=5 Participants
6 participants
n=7 Participants
11 participants
n=5 Participants
Baseline INCAT Score
Total Overall Disability Score
4.2 units on a scale
STANDARD_DEVIATION 1.4 • n=5 Participants
4.1 units on a scale
STANDARD_DEVIATION 1.5 • n=7 Participants
4.2 units on a scale
STANDARD_DEVIATION 1.4 • n=5 Participants
Baseline INCAT Score
Upper Extremity Disability Score
2.3 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
2.1 units on a scale
STANDARD_DEVIATION 1.0 • n=7 Participants
2.2 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
Baseline INCAT Score
Lower Extremity Disability Score
1.9 units on a scale
STANDARD_DEVIATION 0.8 • n=5 Participants
1.9 units on a scale
STANDARD_DEVIATION 1.1 • n=7 Participants
1.9 units on a scale
STANDARD_DEVIATION 0.9 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The Intent-to-Treat Population was defined as all randomized subjects. This population was the primary efficacy population to be analyzed.

The primary efficacy objective was the comparison of IGIV-C and Placebo group Responder rates. An Efficacy Period Responder was defined as a subject with ≥ 1 point improvement in the adjusted Inflammatory Neuropathy Case And Treatment (INCAT) score, with the improvement maintained through the end of Week 24 in the Efficacy Period. Measurements are reported in INCAT scale of 0-5 in both lower and upper extremities, for a total score of 0 to 10. INCAT scores for arm disability: 0 = no upper limb problems; 5 = inability to use either arm for any purposeful movement. INCAT scores for leg disability: 0= walking not affected; 5 = restricted to wheelchair, unable to stand and walk a few steps with help

Outcome measures

Outcome measures
Measure
IGIV-C
n=59 Participants
Placebo
n=58 Participants
Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
54.2 percentage of responders
20.7 percentage of responders

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-treat

Mean changes in amplitude \[mV\] measured at most proximal site in the most severely affected motor nerve from baseline to endpoint during the Efficacy Period (Intent to treat population)

Outcome measures

Outcome measures
Measure
IGIV-C
n=59 Participants
Placebo
n=58 Participants
Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period
0.69 Millivolts
Standard Deviation 1.856
0.47 Millivolts
Standard Deviation 2.291

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure
IGIV-C
n=59 Participants
Placebo
n=58 Participants
Mean Change in Grip Strength During the Efficacy Period
Dominant hand (IGIV-C n=57, Placebo n=58)
13.175 kilopascal
Standard Deviation 19.2935
1.489 kilopascal
Standard Deviation 15.5742
Mean Change in Grip Strength During the Efficacy Period
Non-dominant hand (IGIV-C n=58, Placebo n=58)
13.316 kilopascal
Standard Deviation 17.3526
4.261 kilopascal
Standard Deviation 14.8959

SECONDARY outcome

Timeframe: 6 months

Population: In the Randomized Withdrawal Period, 43 subjects were randomized to IGIV-C, but only 31 out of the 41 subjects were prior IGIV-C responders or rescue successes. Similarly, 31 subjects were randomized to Placebo, but only 26 out of the 31 subjects were prior IGIV-C responders or rescue successes.

Outcome measures

Outcome measures
Measure
IGIV-C
n=31 Participants
Placebo
n=26 Participants
Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period
21.89 weeks
Standard Deviation 6.181
16.56 weeks
Standard Deviation 8.543

Adverse Events

IGIV-C

Serious events: 6 serious events
Other events: 81 other events
Deaths: 0 deaths

Placebo

Serious events: 8 serious events
Other events: 25 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
IGIV-C
n=113 participants at risk
2 g/kg loading dose, followed by 1 g/kg maintenance dose. A total of 113 subjects were exposed to IGIV-C across all three treatments/periods.
Placebo
n=95 participants at risk
.1% albumin; 2g/kg loading dose and 1 g/kg maintenance dose. A total of 95 subjects were exposed to Placebo across all three treatments/periods.
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.88%
1/113 • Number of events 1
0.00%
0/95
Nervous system disorders
Dizziness
0.88%
1/113 • Number of events 1
0.00%
0/95
Cardiac disorders
Palpitations
0.88%
1/113 • Number of events 1
0.00%
0/95
General disorders
Pyrexia
0.88%
1/113 • Number of events 1
0.00%
0/95
Nervous system disorders
Headache
1.8%
2/113 • Number of events 2
0.00%
0/95
Respiratory, thoracic and mediastinal disorders
Dyspnea
0.88%
1/113 • Number of events 1
0.00%
0/95
Gastrointestinal disorders
Vomiting
0.88%
1/113 • Number of events 1
0.00%
0/95
Infections and infestations
Bronchopneumonia
0.88%
1/113 • Number of events 1
0.00%
0/95
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/113
1.1%
1/95 • Number of events 1
Nervous system disorders
Demyelinating polyneuropathy
0.00%
0/113
1.1%
1/95 • Number of events 1
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/113
1.1%
1/95 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Asthma
0.00%
0/113
1.1%
1/95 • Number of events 1
Investigations
Medical observation (for asthma)
0.00%
0/113
1.1%
1/95 • Number of events 1
Infections and infestations
Gastroenteritis viral
0.00%
0/113
1.1%
1/95 • Number of events 1
Nervous system disorders
Cerebrovascular accident
0.00%
0/113
1.1%
1/95 • Number of events 1
Vascular disorders
Deep vein thrombosis
0.00%
0/113
1.1%
1/95 • Number of events 1
Pregnancy, puerperium and perinatal conditions
Pregnancy
0.00%
0/113
1.1%
1/95 • Number of events 1
Nervous system disorders
CIDP (relapse)
0.00%
0/113
1.1%
1/95 • Number of events 1

Other adverse events

Other adverse events
Measure
IGIV-C
n=113 participants at risk
2 g/kg loading dose, followed by 1 g/kg maintenance dose. A total of 113 subjects were exposed to IGIV-C across all three treatments/periods.
Placebo
n=95 participants at risk
.1% albumin; 2g/kg loading dose and 1 g/kg maintenance dose. A total of 95 subjects were exposed to Placebo across all three treatments/periods.
Gastrointestinal disorders
Nausea
6.2%
7/113 • Number of events 9
3.2%
3/95 • Number of events 3
General disorders
Pyrexia
12.4%
14/113 • Number of events 26
0.00%
0/95
General disorders
Asthenia
8.0%
9/113 • Number of events 10
3.2%
3/95 • Number of events 4
General disorders
Chills
8.0%
9/113 • Number of events 10
0.00%
0/95
Infections and infestations
Influenza
5.3%
6/113 • Number of events 6
2.1%
2/95 • Number of events 2
Musculoskeletal and connective tissue disorders
Back pain
7.1%
8/113 • Number of events 9
3.2%
3/95 • Number of events 3
Musculoskeletal and connective tissue disorders
Arthralgia
7.1%
8/113 • Number of events 11
1.1%
1/95 • Number of events 1
Nervous system disorders
Headache
30.1%
34/113 • Number of events 55
8.4%
8/95 • Number of events 15
Nervous system disorders
Dizziness
5.3%
6/113 • Number of events 6
1.1%
1/95 • Number of events 1
Skin and subcutaneous tissue disorders
Rash
7.1%
8/113 • Number of events 13
1.1%
1/95 • Number of events 1
Vascular disorders
Hypertension
8.8%
10/113 • Number of events 20
4.2%
4/95 • Number of events 6

Additional Information

Henry Li

Grifols Therapeutics

Phone: 1-800-520-2807

Results disclosure agreements

  • Principal investigator is a sponsor employee The investigator must send a draft manuscript of the publication or abstract to the sponsor thirty days in advance of submission in order to obtain approval prior to submission of the final version for publication. This will be reviewed promptly and approval will not be withheld unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the contents of the publication will be discussed in order to find a solution that satisfies both parties.
  • Publication restrictions are in place

Restriction type: OTHER