Immune Globulin Intravenous (IGIV) For Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Information source: Grifols Therapeutics Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Intervention: Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (Drug); Albumin (Human) 25%, USP (Drug)
Phase: Phase 3
Sponsored by: Grifols Therapeutics Inc.
Official(s) and/or principal investigator(s):
Norman Latov, MD, Principal Investigator, Affiliation: Columbia University
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 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.
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: ≥ 1 point improvement in the INCAT score relative to baseline at 6 months (without crossing over) or the last INCAT assessment after the first study drug infusion (crossing over). Any subject who crosses over will be considered a non-responder.
Mean change in the amplitude (millivolts) in the most severely affected motor nerve
Change in grip strength
Time to relapse
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.
Eligible subjects will be randomized to receive either IGIV-C at a dose of 2 g/kg body
weight (bw) ideally over 2-4 days or matching placebo. Thereafter, study drug infusion
(IGIV-C or matching 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. Patient's functional disability
will be measured using the INCAT disability score at baseline, day 16, and at each study
visit scheduled every 3 weeks for 6 months. If the INCAT score worsens by ≥1 point at any
time between day 16 and month 6 (not including the month 6 visit) relative to baseline, the
subject will be immediately crossed over to the other study drug. Subjects whose INCAT
upper extremity score changes from 0 to 1 or from 1 to 0 will have an adjusted INCAT score
calculated where this upper extremity change is not incorporated into the adjusted score.
Any subject with an adjusted INCAT score change of 0 will be deemed a stable patient and
will be crossed over at week 6.
Upon entering the crossover period, subjects will receive either IGIV-C at a dose of 2 g/kg
bw ideally over 2-4 days or matching placebo. Thereafter, a study drug infusion (IGIV-C or
matching 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. A subject will be terminated from the study any
time between day 16 and 6 months during the crossover period if the INCAT score fails to
improve by ≥1 point relative to INCAT score at time of crossover. Stable subjects who
crossed over at Week 6 must remain in the Crossover Treatment Period for 3 weeks before
being considered for withdrawal (due to lack of improvement). Any subject who has been
crossed-over to the alternate study drug will be deemed a treatment failure for the primary
Randomization will be within each center. Eight randomization numbers, which constitutes
one or more full random blocks, will be assigned to each center. A random number will be
assigned to subjects in ascending order.
Minimum age: 18 Years.
Maximum age: N/A.
- 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
- 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.)
- 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, 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
- Respiratory impairment requiring mechanical ventilation
- Myelopathy or evidence of central demyelination or persisting neurological deficits
from stroke, 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, IgM paraproteinemia, and amiodarone therapy.
- History of anaphylaxis or severe systemic response to immunoglobulin or with a blood
- 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 IgA deficiency.
- Other investigational drugs received within the 30 days prior to entry
- Conditions whose symptoms and effects could alter protein catabolism and/or 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 TSH and abnormally low
T4) or vitamin B12 deficiency (abnormally low) within the last 3 months prior to
Locations and Contacts
Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI), Buenos Aires C1428 AQK, Argentina
Hospital Frances, Buenos Aires C1221ACI, Argentina
Hospital Ramos Mejia, Buenos Aires C1221 ADC, Argentina
Instituto de Neurociencias Buenos Aires (INEBA), Capital Federal C1192 AAW, Argentina
Fakultní nemocnice Brno, Brno 625 00, Czech Republic
Fakultní nemocnice Ostrava, Ostrava-Poruba 1790, Czech Republic
Neurologická klinika Pardubice, Pardubice 53003, Czech Republic
Fakultní nemocnice Motol, Praha 5 15600, Czech Republic
Jüdisches Krankenhaus, Berlin 13347, Germany
Tel Aviv Sourasky Medical Center, Tel Aviv 84101, Israel
Chaim Sheba Medical Center, Tel Hashomer, Israel
Assaf Harofe Medical Center, Zrifin 70300, Israel
Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti, Chieti, Italy
Univesita delgi Studi di Genova, Dipartimento di Scienze, Neurologiche e della Visione, Genova 16132, Italy
Hospital San Raffaele, Milano 20132, Italy
Hospital Central San Luis Potosi, Neurology Department, San Luis Potosi, Mexico
Centre of Clinical Neurology, Neurology Department, Cracow 31-530, Poland
County Specialist Hospital, Neurology Department, Gdansk 80-803, Poland
Barlicki Hospital, Lodz 90-153, Poland
Medical Acedemy, Clinical Hospital, Neurology Department, Lubin 20-950, Poland
Central Clinical Hospital, Medical Academy Warsaw, Warsaw, Poland
County Hospital, Zgierz, Poland
University Hospital, University of Belgrade, Belgrade 11000, Serbia
Vancouver Hospital and Health Sciences Center, Vancouver, British Columbia V5Z 1M9, Canada
Yale University School of Medicine, New Haven, Connecticut 06520-8018, United States
Antiguo Hospital Civil de Guadalajara, Guadalajara, Jalisco 44280, Mexico
Hospital Angel Leano, Neurology Department, Guadalajara, Jalisco, Mexico
Saint Louis University Medical Center, St. Louis, Missouri 63110, United States
Columbia University, New York, New York 10022, United States
Wake Forest University-School of Medicine, Winston-Salem, North Carolina 27157-1078, United States
Cleveland Clinic, Cleveland, Ohio 44195, United States
University of Texas-Southwestern Medical Center at Dallas, Dallas, Texas 75390, United States
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Starting date: April 2004
Last updated: August 4, 2009