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

This study has been completed.
Sponsor:
Information provided by:
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00220740
First received: September 13, 2005
Last updated: August 4, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Drug: Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified
Drug: Albumin (Human) 25%, USP
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • ≥ 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. [ Time Frame: 6 month ]

Secondary Outcome Measures:
  • Mean change in the amplitude (millivolts) in the most severely affected motor nerve [ Time Frame: 6 or 12 month ]
  • Change in grip strength [ Time Frame: 6 or 12 month ]
  • Time to relapse [ Time Frame: 6 month ]

Enrollment: 117
Study Start Date: April 2004
Study Completion Date: June 2006
Arms Assigned Interventions
Experimental: Group 1
IGIV-C
Drug: Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified
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
Other Names:
  • 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
Placebo Comparator: Group 2 Drug: Albumin (Human) 25%, USP
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
Other Names:
  • 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

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.

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 efficacy analysis.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, 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, 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 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 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 entry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00220740

  Show 32 Study Locations
Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Norman Latov, MD Columbia University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00220740     History of Changes
Other Study ID Numbers: 100538
Study First Received: September 13, 2005
Last Updated: August 4, 2009
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Czech Republic: State Institute for Drug Control
Italy: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Germany: Federal Institute for Drugs and Medical Devices
Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Grifols Therapeutics Inc.:
Immunoglobulin G

Additional relevant MeSH terms:
Polyneuropathies
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Demyelinating Diseases
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014