Clinical trial NCT00220740: Immune Globulin Intravenous (IGIV) For Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Keywords: Immunoglobulin G
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
timeFrame: 6 months
Secondary outcomes:
measure: Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period
timeFrame: 6 months
measure: Mean Change in Grip Strength During the Efficacy Period
timeFrame: 6 months
measure: Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period
timeFrame: 6 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: St. Louis
country: United States
facility: Saint Louis University Medical Center
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University-School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: University of Texas-Southwestern Medical Center at Dallas
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Ramos Mejia
city: Buenos Aires
country: Argentina
facility: Hospital Frances
city: Buenos Aires
country: Argentina
facility: Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI)
city: Capital Federal
country: Argentina
facility: Instituto de Neurociencias Buenos Aires (INEBA)
city: Vancouver
country: Canada
facility: Vancouver Hospital and Health Sciences Center
state: British Columbia
city: Brno
country: Czech Republic
facility: Fakultní nemocnice Brno
city: Ostrava-Poruba
country: Czech Republic
facility: Fakultní nemocnice Ostrava
city: Pardubice
country: Czech Republic
facility: Neurologická klinika Pardubice
city: Praha 5
country: Czech Republic
facility: Fakultní nemocnice Motol
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Zrifin
country: Israel
facility: Assaf Harofe Medical Center
city: Chieti
country: Italy
facility: Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti
city: Genova
country: Italy
facility: Univesita delgi Studi di Genova, Dipartimento di Scienze, Neurologiche e della Visione
city: Milano
country: Italy
facility: Hospital San Raffaele
city: Guadalajara
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara
state: Jalisco
city: Guadalajara
country: Mexico
facility: Hospital Angel Leano, Neurology Department
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: Hospital Central San Luis Potosi, Neurology Department
city: Cracow
country: Poland
facility: Centre of Clinical Neurology, Neurology Department
city: Gdansk
country: Poland
facility: County Specialist Hospital, Neurology Department
city: Lodz
country: Poland
facility: Barlicki Hospital
city: Lubin
country: Poland
facility: Medical Acedemy, Clinical Hospital, Neurology Department
city: Warsaw
country: Poland
facility: Central Clinical Hospital, Medical Academy Warsaw
city: Zgierz
country: Poland
facility: County Hospital
city: Belgrade
country: Serbia
facility: University Hospital, University of Belgrade
Study officials:
affiliation: Columbia University
name: Norman Latov, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.