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

Primary Purpose

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Immune Globulin IV (Human), 10% Caprylate/Chromatography Purified
Albumin (Human) 25%, United States Pharmacopeia (USP)
Sponsored by
Grifols Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polyradiculoneuropathy, Chronic Inflammatory Demyelinating focused on measuring Immunoglobulin G

Eligibility Criteria

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

Inclusion Criteria: Documented diagnosis of CIDP must be made by a neurologist specializing/experienced in neuromuscular diseases based on: a) Progressive or relapsing motor and sensory dysfunction of more than one limb resulting from neuropathy over the 2 months prior to the date informed consent is obtained, and b) Cerebrospinal fluid (CSF) less than 50 white cells/µl since CIDP diagnosis (CSF testing studies are NOT mandatory) Fulfillment of INCAT neurophysiological criteria for focal demyelinating polyradiculoneuropathy Overall INCAT score between 2-9 and significant disability in upper or lower limb function in at least 2 limbs. (An INCAT score of 2 must be exclusively from leg disability to qualify.) Exclusion Criteria: Treatment with IGIV or plasma within 3 months prior to entry Steroids (Prednisolone or equivalent) > 10 mg/day or equivalent (i.e., > 20 mg every 2 days) during the last 3 months prior to entry Treatment with immunomodulatory/immunosuppressive agents (azathioprin, tacrolimus,cyclosporin, Muromonab-CD3 (OKT3), any interferon), previous lymphoid irradiation or prior treatment with cyclophosphamide, methotrexate, mitoxantrone or any other immunosuppressant drug within the past 6 months prior to entry Concomitant use of supplements containing any amount of fish oil within 30 days prior to entry Respiratory impairment requiring mechanical ventilation Myelopathy or evidence of central demyelination or persisting neurological deficits from stroke, central nervous system (CNS) trauma or peripheral neuropathies of other cause which include diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), uremic, toxic and familial neuropathies Pure motor syndrome fulfilling criteria for multifocal motor neuropathy with conduction block. Lower motor neuron disorder with motor weakness in an upper limb, without sensory deficit and with proximal conduction block (50% decrease in amplitude/area with proximal distal stimulation ) in motor nerves and normal sensory nerve conduction studies. Clinical or known evidence of associated systemic diseases that might cause neuropathy, including but not limited to connective tissue disease, HIV infection, hepatitis, Lyme disease, cancer (with the exception of benign skin cancer), Castleman's disease and systemic lupus erythematosus, diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), a malignant plasma cell dysplasia, immunoglobulin M (IgM) paraproteinemia, and amiodarone therapy. History of anaphylaxis or severe systemic response to immunoglobulin or with a blood product. Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic pressure >120 mmHg or systolic >170 mmHg). Females who are pregnant, breast feeding, or if of childbearing potential, unwilling to practice adequate contraception throughout the study. Known hyperviscosity. History of renal insufficiency or serum creatinine levels > 221 µmol/L (2.5 mg/dL). Known selective immunoglobulin A (IgA) deficiency. Other investigational drugs received within the 30 days prior to entry Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome). Known hypercoagulable state. Mentally challenged adult subjects who cannot give independent informed consent. Subjects with uncompensated hypothyroidism (abnormally high thyroid-stimulating hormone (TSH) and abnormally low T4) or vitamin B12 deficiency (abnormally low) within the last 3 months prior to entry.

Sites / Locations

  • Yale University School of Medicine
  • Saint Louis University Medical Center
  • Columbia University
  • Wake Forest University-School of Medicine
  • Cleveland Clinic
  • University of Texas-Southwestern Medical Center at Dallas
  • Hospital Ramos Mejia
  • Hospital Frances
  • Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI)
  • Instituto de Neurociencias Buenos Aires (INEBA)
  • Vancouver Hospital and Health Sciences Center
  • Fakultní nemocnice Brno
  • Fakultní nemocnice Ostrava
  • Neurologická klinika Pardubice
  • Fakultní nemocnice Motol
  • Jüdisches Krankenhaus
  • Tel Aviv Sourasky Medical Center
  • Chaim Sheba Medical Center
  • Assaf Harofe Medical Center
  • Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti
  • Univesita delgi Studi di Genova, Dipartimento di Scienze, Neurologiche e della Visione
  • Hospital San Raffaele
  • Antiguo Hospital Civil de Guadalajara
  • Hospital Angel Leano, Neurology Department
  • Hospital Central San Luis Potosi, Neurology Department
  • Centre of Clinical Neurology, Neurology Department
  • County Specialist Hospital, Neurology Department
  • Barlicki Hospital
  • Medical Acedemy, Clinical Hospital, Neurology Department
  • Central Clinical Hospital, Medical Academy Warsaw
  • County Hospital
  • University Hospital, University of Belgrade

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1

Group 2

Arm Description

IGIV-C

Outcomes

Primary Outcome Measures

Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
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

Secondary Outcome Measures

Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period
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)
Mean Change in Grip Strength During the Efficacy Period
Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period

Full Information

First Posted
September 13, 2005
Last Updated
February 23, 2016
Sponsor
Grifols Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00220740
Brief Title
Immune Globulin Intravenous (IGIV) For Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Acronym
ICE
Official Title
Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of IGIV-Chromatography (IGIV-C), 10% Treatment in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
June 2006 (Actual)
Study Completion Date
June 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The intent of this study is to demonstrate the efficacy and safety of Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in newly or previously diagnosed CIDP subjects. Eight courses of treatment with either placebo or IGIV-C will occur every 3 weeks. Neurological function will be measured by Inflammatory Neuropathy Cause and Treatment (INCAT) scores. Patients who deteriorate or show no improvement between day 16 and month 6 will receive the alternate study drug for an additional 6 months.
Detailed Description
110 subjects, 55 per treatment group, with newly or previously diagnosed CIDP defined by INCAT neurophysiological diagnostic criteria will be enrolled into the trial. Patients will not be replaced if they discontinue prematurely.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Keywords
Immunoglobulin G

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
117 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
IGIV-C
Arm Title
Group 2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Immune Globulin IV (Human), 10% Caprylate/Chromatography Purified
Other Intervention Name(s)
IGIV-C, IGIV-Chromatography (IGIV-C), 10%, Gamunex®, Gaminex®, IGIVnex, Intravenous Immunoglobulin (Human) (IGIV), Intravenous Immunoglobulin (Human), IVIG, IGIV, Intravenous Immune Globulin (Human), TAL-05-00004, Bay 41-1000, NDC13533-645-12, NDC13533-645-15, NDC13533-645-20, NDC13533-645-71, NDC13533-645-24
Intervention Description
2 g/kg body weight ideally over 2-4 days . Thereafter, study drug infusion (IGIV-C) will be administered every 3 weeks at a dose of 1 g/kg bw, given over 1-2 days for a total of 7 additional infusions
Intervention Type
Drug
Intervention Name(s)
Albumin (Human) 25%, United States Pharmacopeia (USP)
Other Intervention Name(s)
Albumin (Human) 25%, USP, Plasbumin®-25, Plasbumin®-25 (Low Aluminum), TAL-05-00009, TAL-05-00025, Bay 34-9255, NDC 13533-684-16, NDC 13533-684-20, NDC 13533-684-71, NDC 13533-692-16, NDC 13533-692-20, NDC 13533-692-71
Intervention Description
Albumin 25%, USP diluted with dextrose 5% to a final concentration of 0.1% as an intravenous infusion. Alternatively, it may be a bottled placebo of 0.1% Albumin (Human) in 0.2 M Glycine, 1.1 mm sodium caprylate, 0.25% sodium chloride. 2 g/kg body weight ideally over 2-4 days . Thereafter, infusion (placebo) will be administered every 3 weeks at a dose of 1 g/kg bw, given over 1-2 days for a total of 7 additional infusions
Primary Outcome Measure Information:
Title
Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period
Description
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)
Time Frame
6 months
Title
Mean Change in Grip Strength During the Efficacy Period
Time Frame
6 months
Title
Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented diagnosis of CIDP must be made by a neurologist specializing/experienced in neuromuscular diseases based on: a) Progressive or relapsing motor and sensory dysfunction of more than one limb resulting from neuropathy over the 2 months prior to the date informed consent is obtained, and b) Cerebrospinal fluid (CSF) less than 50 white cells/µl since CIDP diagnosis (CSF testing studies are NOT mandatory) Fulfillment of INCAT neurophysiological criteria for focal demyelinating polyradiculoneuropathy Overall INCAT score between 2-9 and significant disability in upper or lower limb function in at least 2 limbs. (An INCAT score of 2 must be exclusively from leg disability to qualify.) Exclusion Criteria: Treatment with IGIV or plasma within 3 months prior to entry Steroids (Prednisolone or equivalent) > 10 mg/day or equivalent (i.e., > 20 mg every 2 days) during the last 3 months prior to entry Treatment with immunomodulatory/immunosuppressive agents (azathioprin, tacrolimus,cyclosporin, Muromonab-CD3 (OKT3), any interferon), previous lymphoid irradiation or prior treatment with cyclophosphamide, methotrexate, mitoxantrone or any other immunosuppressant drug within the past 6 months prior to entry Concomitant use of supplements containing any amount of fish oil within 30 days prior to entry Respiratory impairment requiring mechanical ventilation Myelopathy or evidence of central demyelination or persisting neurological deficits from stroke, central nervous system (CNS) trauma or peripheral neuropathies of other cause which include diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), uremic, toxic and familial neuropathies Pure motor syndrome fulfilling criteria for multifocal motor neuropathy with conduction block. Lower motor neuron disorder with motor weakness in an upper limb, without sensory deficit and with proximal conduction block (50% decrease in amplitude/area with proximal distal stimulation ) in motor nerves and normal sensory nerve conduction studies. Clinical or known evidence of associated systemic diseases that might cause neuropathy, including but not limited to connective tissue disease, HIV infection, hepatitis, Lyme disease, cancer (with the exception of benign skin cancer), Castleman's disease and systemic lupus erythematosus, diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), a malignant plasma cell dysplasia, immunoglobulin M (IgM) paraproteinemia, and amiodarone therapy. History of anaphylaxis or severe systemic response to immunoglobulin or with a blood product. Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic pressure >120 mmHg or systolic >170 mmHg). Females who are pregnant, breast feeding, or if of childbearing potential, unwilling to practice adequate contraception throughout the study. Known hyperviscosity. History of renal insufficiency or serum creatinine levels > 221 µmol/L (2.5 mg/dL). Known selective immunoglobulin A (IgA) deficiency. Other investigational drugs received within the 30 days prior to entry Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome). Known hypercoagulable state. Mentally challenged adult subjects who cannot give independent informed consent. Subjects with uncompensated hypothyroidism (abnormally high thyroid-stimulating hormone (TSH) and abnormally low T4) or vitamin B12 deficiency (abnormally low) within the last 3 months prior to entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norman Latov, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8018
Country
United States
Facility Name
Saint Louis University Medical Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Facility Name
Wake Forest University-School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1078
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Texas-Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Hospital Ramos Mejia
City
Buenos Aires
ZIP/Postal Code
C1221 ADC
Country
Argentina
Facility Name
Hospital Frances
City
Buenos Aires
ZIP/Postal Code
C1221ACI
Country
Argentina
Facility Name
Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI)
City
Buenos Aires
ZIP/Postal Code
C1428 AQK
Country
Argentina
Facility Name
Instituto de Neurociencias Buenos Aires (INEBA)
City
Capital Federal
ZIP/Postal Code
C1192 AAW
Country
Argentina
Facility Name
Vancouver Hospital and Health Sciences Center
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
Fakultní nemocnice Brno
City
Brno
ZIP/Postal Code
625 00
Country
Czech Republic
Facility Name
Fakultní nemocnice Ostrava
City
Ostrava-Poruba
ZIP/Postal Code
1790
Country
Czech Republic
Facility Name
Neurologická klinika Pardubice
City
Pardubice
ZIP/Postal Code
53003
Country
Czech Republic
Facility Name
Fakultní nemocnice Motol
City
Praha 5
ZIP/Postal Code
15600
Country
Czech Republic
Facility Name
Jüdisches Krankenhaus
City
Berlin
ZIP/Postal Code
13347
Country
Germany
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
84101
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Tel Hashomer
Country
Israel
Facility Name
Assaf Harofe Medical Center
City
Zrifin
ZIP/Postal Code
70300
Country
Israel
Facility Name
Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti
City
Chieti
Country
Italy
Facility Name
Univesita delgi Studi di Genova, Dipartimento di Scienze, Neurologiche e della Visione
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Hospital San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Antiguo Hospital Civil de Guadalajara
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Hospital Angel Leano, Neurology Department
City
Guadalajara
State/Province
Jalisco
Country
Mexico
Facility Name
Hospital Central San Luis Potosi, Neurology Department
City
San Luis Potosi
Country
Mexico
Facility Name
Centre of Clinical Neurology, Neurology Department
City
Cracow
ZIP/Postal Code
31-530
Country
Poland
Facility Name
County Specialist Hospital, Neurology Department
City
Gdansk
ZIP/Postal Code
80-803
Country
Poland
Facility Name
Barlicki Hospital
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
Facility Name
Medical Acedemy, Clinical Hospital, Neurology Department
City
Lubin
ZIP/Postal Code
20-950
Country
Poland
Facility Name
Central Clinical Hospital, Medical Academy Warsaw
City
Warsaw
Country
Poland
Facility Name
County Hospital
City
Zgierz
Country
Poland
Facility Name
University Hospital, University of Belgrade
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia

12. IPD Sharing Statement

Citations:
PubMed Identifier
18178525
Citation
Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn PA; ICE Study Group. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008 Feb;7(2):136-44. doi: 10.1016/S1474-4422(07)70329-0. Erratum In: Lancet Neurol. 2008 Sep;7(9):771.
Results Reference
result
PubMed Identifier
19260050
Citation
Bril V, Katzberg H, Donofrio P, Banach M, Dalakas MC, Deng C, Hanna K, Hartung HP, Hughes RA, Latov N, Merkies IS, van Doorn PA; ICE Study Group. Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV. Muscle Nerve. 2009 Apr;39(4):448-55. doi: 10.1002/mus.21236.
Results Reference
result
PubMed Identifier
19365055
Citation
Merkies IS, Bril V, Dalakas MC, Deng C, Donofrio P, Hanna K, Hartung HP, Hughes RA, Latov N, van Doorn PA; ICE Study Group. Health-related quality-of-life improvements in CIDP with immune globulin IV 10%: the ICE Study. Neurology. 2009 Apr 14;72(15):1337-44. doi: 10.1212/WNL.0b013e3181a0fd80.
Results Reference
result
PubMed Identifier
19496683
Citation
Hughes RA. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy: the ICE trial. Expert Rev Neurother. 2009 Jun;9(6):789-95. doi: 10.1586/ern.09.30.
Results Reference
result
PubMed Identifier
20837852
Citation
Donofrio PD, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Hughes R, Latov N, Merkies I, van Doorn P; IGIV-C CIDP Efficacy (ICE) Study Group. Safety and tolerability of immune globulin intravenous in chronic inflammatory demyelinating polyradiculoneuropathy. Arch Neurol. 2010 Sep;67(9):1082-8. doi: 10.1001/archneurol.2010.223. Erratum In: Arch Neurol. 2010 Dec; 67(12):1515.
Results Reference
derived
PubMed Identifier
20647554
Citation
Merkies IS, van Nes SI, Hanna K, Hughes RA, Deng C. Confirming the efficacy of intravenous immunoglobulin in CIDP through minimum clinically important differences: shifting from statistical significance to clinical relevance. J Neurol Neurosurg Psychiatry. 2010 Nov;81(11):1194-9. doi: 10.1136/jnnp.2009.194324. Epub 2010 Jul 20.
Results Reference
derived
PubMed Identifier
20457948
Citation
Latov N, Deng C, Dalakas MC, Bril V, Donofrio P, Hanna K, Hartung HP, Hughes RA, Merkies IS, van Doorn PA; IGIV-C CIDP Efficacy (ICE) Study Group. Timing and course of clinical response to intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. Arch Neurol. 2010 Jul;67(7):802-7. doi: 10.1001/archneurol.2010.105. Epub 2010 May 10.
Results Reference
derived
Links:
URL
http://www.talecris-pi.info/inserts/gamunex.pdf
Description
FDA Approved Product Labeling Information - Gamunex®
URL
http://www.talecris-pi.info/inserts/plasbumin25la.pdf
Description
FDA Approved Product Labeling Information - Plasbumin®-25 (Low Aluminum)

Learn more about this trial

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

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