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

NCT00220740 | Completed Phase 3 Results

• 1 other identifier: 100538
• Study Type: interventional
• Target: 117
• Locations: 10 countries
• Sites: 32

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.

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Keywords

Immunoglobulin G

Outcome Measures

Primary Outcomes (1)

• 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 months

Secondary Outcomes (3)

• Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period

  6 months

• Mean Change in Grip Strength During the Efficacy Period

  6 months

• Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period

  6 months

Study Arms (2)

Group 1

EXPERIMENTAL

IGIV-C

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

Group 2

PLACEBO COMPARATOR

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

Interventions

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

Also known as: 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

Group 1

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

Also known as: 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

Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (32)

Yale University School of Medicine

New Haven, Connecticut, 06520-8018, United States

Location

Saint Louis University Medical Center

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10022, United States

Location

Wake Forest University-School of Medicine

Winston-Salem, North Carolina, 27157-1078, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Texas-Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Hospital Ramos Mejia

Buenos Aires, C1221 ADC, Argentina

Location

Hospital Frances

Buenos Aires, C1221ACI, Argentina

Location

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

Buenos Aires, C1428 AQK, Argentina

Location

Instituto de Neurociencias Buenos Aires (INEBA)

Capital Federal, C1192 AAW, Argentina

Location

Vancouver Hospital and Health Sciences Center

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Fakultní nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava-Poruba, 1790, Czechia

Location

Neurologická klinika Pardubice

Pardubice, 53003, Czechia

Location

Fakultní nemocnice Motol

Prague, 15600, Czechia

Location

Jüdisches Krankenhaus

Berlin, 13347, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 84101, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, Israel

Location

Assaf Harofe Medical Center

Zrifin, 70300, Israel

Location

Dipartimento di Neuroscienze, Sezione di Neurologia, AO Chieti

Chieti, Italy

Location

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

Genova, 16132, Italy

Location

Hospital San Raffaele

Milan, 20132, Italy

Location

Antiguo Hospital Civil de Guadalajara

Guadalajara, Jalisco, 44280, Mexico

Location

Hospital Angel Leano, Neurology Department

Guadalajara, Jalisco, Mexico

Location

Hospital Central San Luis Potosi, Neurology Department

San Luis Potosí City, Mexico

Location

County Specialist Hospital, Neurology Department

Gdansk, 80-803, Poland

Location

Centre of Clinical Neurology, Neurology Department

Krakow, 31-530, Poland

Location

Barlicki Hospital

Lodz, 90-153, Poland

Location

Medical Acedemy, Clinical Hospital, Neurology Department

Lubin, 20-950, Poland

Location

Central Clinical Hospital, Medical Academy Warsaw

Warsaw, Poland

Location

County Hospital

Zgierz, Poland

Location

University Hospital, University of Belgrade

Belgrade, 11000, Serbia

Location

Related Publications (7)

• 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.

  PMID: 18178525 RESULT

• 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.

  PMID: 19260050 RESULT

• 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.

  PMID: 19365055 RESULT

• 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.

  PMID: 19496683 RESULT

• 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.

  PMID: 20837852 DERIVED

• 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.

  PMID: 20647554 DERIVED

• 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.

  PMID: 20457948 DERIVED

Related Links

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

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

gamma-Globulins; Caprylates; Immunoglobulins, Intravenous; Albumins

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies

Results Point of Contact

• Title: Henry Li
• Organization: Grifols Therapeutics

henry.li@grifols.com

1-800-520-2807

Study Officials

• Norman Latov, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 22, 2005
• Study Start: April 1, 2004
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: March 23, 2016
• Results First Posted: September 10, 2015

Record last verified: 2016-02

Locations

IL (3); CA (1); DE (1); US (6); ME (3); CZ (4); AR (4); PL (6); IT (3); SE (1)