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

NCT ID: NCT00220740

Last Updated: 2016-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2006-06-30

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.

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

IGIV-C

Group Type: EXPERIMENTAL

Immune Globulin IV (Human), 10% Caprylate/Chromatography Purified

Intervention Type: DRUG

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

Group 2

Group Type: PLACEBO_COMPARATOR

Albumin (Human) 25%, United States Pharmacopeia (USP)

Intervention Type: DRUG

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

Interventions

Immune Globulin IV (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

Intervention Type: DRUG

Albumin (Human) 25%, United States Pharmacopeia (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

Intervention Type: DRUG

Other Intervention 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; 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Norman Latov, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

Saint Louis University Medical Center

St Louis, Missouri, United States

Columbia University

New York, New York, United States

Wake Forest University-School of Medicine

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Texas-Southwestern Medical Center at Dallas

Dallas, Texas, United States

Hospital Ramos Mejia

Buenos Aires, , Argentina

Hospital Frances

Buenos Aires, , Argentina

Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI)

Buenos Aires, , Argentina

Instituto de Neurociencias Buenos Aires (INEBA)

Capital Federal, , Argentina

Vancouver Hospital and Health Sciences Center

Vancouver, British Columbia, Canada

Fakultní nemocnice Brno

Brno, , Czechia

Fakultní nemocnice Ostrava

Ostrava-Poruba, , Czechia

Neurologická klinika Pardubice

Pardubice, , Czechia

Fakultní nemocnice Motol

Prague, , Czechia

Jüdisches Krankenhaus

Berlin, , Germany

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Assaf Harofe Medical Center

Zrifin, , Israel

Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti

Chieti, , Italy

Univesita delgi Studi di Genova, Dipartimento di Scienze, Neurologiche e della Visione

Genova, , Italy

Hospital San Raffaele

Milan, , Italy

Antiguo Hospital Civil de Guadalajara

Guadalajara, Jalisco, Mexico

Hospital Angel Leano, Neurology Department

Guadalajara, Jalisco, Mexico

Hospital Central San Luis Potosi, Neurology Department

San Luis Potosí City, , Mexico

County Specialist Hospital, Neurology Department

Gdansk, , Poland

Centre of Clinical Neurology, Neurology Department

Krakow, , Poland

Barlicki Hospital

Lodz, , Poland

Medical Acedemy, Clinical Hospital, Neurology Department

Lubin, , Poland

Central Clinical Hospital, Medical Academy Warsaw

Warsaw, , Poland

County Hospital

Zgierz, , Poland

University Hospital, University of Belgrade

Belgrade, , Serbia

Countries

United States; Argentina; Canada; Czechia; Germany; Israel; Italy; Mexico; Poland; Serbia

References

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.

Reference Type: RESULT

PMID: 18178525 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19260050 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19365055 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19496683 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20837852 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20647554 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20457948 (View on PubMed)

Related Links

http://www.talecris-pi.info/inserts/gamunex.pdf

FDA Approved Product Labeling Information - Gamunex®

http://www.talecris-pi.info/inserts/plasbumin25la.pdf

FDA Approved Product Labeling Information - Plasbumin®-25 (Low Aluminum)

Other Identifiers

100538

Identifier Type: -

Identifier Source: org_study_id