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

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00220740
• Other study ID #: 100538
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: August 10, 2015
• Start date: April 2004
• Est. completion date: June 2006

Study information

• Verified date: August 2015
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCzech Republic: State Institute for Drug ControlItaly: Ministry of HealthMexico: Federal Commission for Protection Against Health RisksPoland: Ministry of HealthIsrael: Israeli Health Ministry Pharmaceutical AdministrationGermany: Federal Institute for Drugs and Medical DevicesSerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Polyneuropathies
• Polyradiculoneuropathy
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Argentina	Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infacia (FLENI)	Buenos Aires
Argentina	Hospital Frances	Buenos Aires
Argentina	Hospital Ramos Mejia	Buenos Aires
Argentina	Instituto de Neurociencias Buenos Aires (INEBA)	Capital Federal
Canada	Vancouver Hospital and Health Sciences Center	Vancouver	British Columbia
Czech Republic	Fakultní nemocnice Brno	Brno
Czech Republic	Fakultní nemocnice Ostrava	Ostrava-Poruba
Czech Republic	Neurologická klinika Pardubice	Pardubice
Czech Republic	Fakultní nemocnice Motol	Praha 5
Germany	Jüdisches Krankenhaus	Berlin
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Chaim Sheba Medical Center	Tel Hashomer
Israel	Assaf Harofe Medical Center	Zrifin
Italy	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	Milano
Mexico	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 Potosi
Poland	Centre of Clinical Neurology, Neurology Department	Cracow
Poland	County Specialist Hospital, Neurology Department	Gdansk
Poland	Barlicki Hospital	Lodz
Poland	Medical Acedemy, Clinical Hospital, Neurology Department	Lubin
Poland	Central Clinical Hospital, Medical Academy Warsaw	Warsaw
Poland	County Hospital	Zgierz
Serbia	University Hospital, University of Belgrade	Belgrade
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas-Southwestern Medical Center at Dallas	Dallas	Texas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Saint Louis University Medical Center	St. Louis	Missouri
United States	Wake Forest University-School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czech Republic,  Germany,  Israel,  Italy,  Mexico,  Poland,  Serbia, 

References & Publications (4)

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 — View 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 polyrad — View 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. Review. — View 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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 month	No
Secondary	Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period		6 or 12 month	No
Secondary	Mean Change in Grip Strength During the Efficacy Period		6 or 12 month	No
Secondary	Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period		6 month	Yes

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