Immune Globulin Intravenous (IGIV) To Treat Relapsing, Remitting Multiple Sclerosis

NCT ID: NCT00220779

Last Updated: 2016-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31
• Study Completion Date: 2005-02-28

Brief Summary

The trial will study 2 doses of Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (IGIV-C) for the number of relapses that occur in a 1 year treatment period.

Detailed Description

This trial is designed as a multi-national, randomized, double-blind, placebo-controlled prospective trial with three parallel groups.

One hundred twenty (120) patients, 40 per treatment arm, with relapsing-remitting (RR) multiple sclerosis will be enrolled in this trial. Eligible patients must have a diagnosis of MS as per the McDonald Criteria. In addition, patients must have a diagnosis of relapsing-remitting course of MS defined as periods of worsening of neurological function with full recovery or with sequelae and residual deficit upon recovery; periods between disease relapses characterized by lack of disease progression. Patients must also have active disease with at least 1 defined documented relapse in the last year.

During a 2 month run-in period, 2 MRIs will be performed 6 weeks apart and patients will be stratified based on the presence or absence of 1 or more Gadolinium enhancing lesions on the first MRI (Gd-enhancing lesion yes-no) and will be randomized to one of two dose regimens of IGIV-C or matching placebo. Patients will receive study drug infusions every 4 weeks for 48 weeks for a total of 12 infusions. Patients will be evaluated by MRI every 6 weeks and by clinical assessments every 3 months. A follow-up visit will occur 4 weeks after the last infusion.

The treatment groups are as follows:

• IGIV-C - 0.2 g/kg body weight (bw)/infusion (2 ml/kg bw)
• IGIV-C - 0.4 g/kg bw/infusion (4 ml/kg bw)
• placebo (0.1% albumin) - 4 ml/kg bw/infusion

For blinding purposes, at each infusion, all patients will receive a total volume of 4 ml/kg bw. For patients receiving 0.2 g/kg bw of IGIV-C, the final volume of 4 ml/kg bw will be adjusted by the addition of dextrose 5%. Placebo will be supplied as Albumin 5% or Albumin 25% and diluted with either dextrose 5% or saline to a final concentration of 0.1% albumin.

Dose adaptation will be performed for subsequent infusions in case the patient's body weight has changed > 10%. The maximum amount available per infusion will be 400 ml (8 vials) calculated for a patient with a body weight of 100 kg. The suggested initial infusion rate will be 0.02 ml/kg/min for the first 15 minutes. If there is no evidence of a hypersensitivity reaction, the infusion may be given at a slowly increasing rate over the next 30 minutes up to a maximum allowable rate of 0.08 ml/kg/min. As such, the infusion for a 70 kg patient will take approximately 1hour 15 min. The overall infusion time may have a range from 1 to 2 hours.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

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

Study Groups

Group 1

IGIV-C 0.2 g/kg bw/infusion (2 ml/kg bw)

Group Type: EXPERIMENTAL

Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified

Intervention Type: DRUG

Group 2

IGIV-C 0.4 g/kg bw/infusion (4 ml/kg bw)

Group Type: EXPERIMENTAL

Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified

Intervention Type: DRUG

Group 3

placebo (0.1% albumin) 4 ml/kg bw/infusion

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: DRUG

Interventions

Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Gamunex®; IGIVnex®; Gaminex; IGIV-C; Immune Globulin Intravenous (Human) , 10%; IGIV; BAY 41-1000; TAL-05-00004; IGIV-C, 10%; IVIG; Immune Globulin (Human), 10% (IGIV); Immune Globulin Intravenous, 10% by Chromatography Process; NDC 13533-645-12; NDC 13533-645-15; NDC 13533-645-20; NDC 13533-645-24; NDC 13533-645-71; Plasbumin®-5; Plasbumin®-25; Plasbumin®-5 (Low Aluminum); Plasbumin®-25 (Low Aluminum); Albumin (Human) 5%, USP; Albumin (Human) 25%, USP; TAL-05-00009; TAL-05-00023; TAL-05-00025; TAL-05-00026; BAY 34-9255; NDC 13533-684-16; NDC 13533-684-25; NDC 13533-684-71; NDC 13533-685-20; NDC 13533-685-25; NDC 13533-685-27; NDC 13533-690-20; NDC 13533-690-25; NDC 13533-690-27; NDC 13533-692-16; NDC 13533-692-20; NDC 13533-692-71

Eligibility Criteria

Inclusion Criteria

• Symptoms consistent with Multiple Sclerosis up to 5 years
• Diagnosis of multiple sclerosis according to McDonald criteria.
• Diagnosis of relapsing-remitting (RR) multiple sclerosis (MS) (Defined as periods of worsening of neurological function with full recovery or with sequelae and residual deficit upon recovery; periods between disease relapses characterized by lack of disease progression
• Kurtzke Extended Disability Status Scale (EDSS) < 5.0
• At least 1 defined and documented relapse during the last year. Prior relapses where symptoms were due solely to a change in Bowel/Bladder Function or Cognitive Function will not be considered relapses as defined by this protocol and therefore not counted for inclusion into the study.
• Females or males; females of childbearing potential must use adequate contraception
• Clinically stable for at least 30 days prior to entry
• At least 9 hyperintense T2 lesions on MRI or 1 Gd-enhancing lesion according to McDonald/Barkhof dissemination-in-space criteria at entry
• Patients who have been informed about available treatments and decided, not to go on these treatments
• Written informed consent obtained prior to the initiation of any study related procedures

Exclusion Criteria

• Females who are pregnant, breast feeding, or if, of childbearing potential, unwilling to practice adequate contraception throughout the study
• Prior therapy with azathioprine or any immunosuppressant agents within 6 months prior to study entry
• Prior steroid, methylprednisolone or adrenocorticotropic hormone (ACTH) therapy within 30 days prior to study entry
• Therapy with interferons (Betaseron®, Avonex®, Rebif®), glatiramer acetate (Copaxone®) or IGIV within 3 months prior to study entry or during the study
• Use of an investigational compound within 6 months prior to study entry
• Previous lymphoid irradiation or prior to treatment with cyclophosphamide, methotrexate or mitoxantrone
• Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease (CCS III or IV), or malignant hypertension
• History of renal insufficiency or serum creatinine levels greater than 2.5 mg/dL (221 µmol/L)
• Known selective immunoglobulin A (IgA) deficiency or known antibodies to IgA
• Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g., protein-losing enteropathies, nephrotic syndrome)
• Any medical, psychiatric or other circumstances which impede or restrict the patient's participation in the study or any contraindication to contrast enhanced MRI (e.g.,pacemaker, aortic clip or any metal implant)
• Patients with clinically significant medical conditions including, but not limited to cardiac, pulmonary, hepatic, hematological (e.g. known coagulation disorder, history of deep venous thrombosis and/or pulmonary embolism), endocrine,or renal dysfunction, autoimmune disorders, severe environmental allergies or chronic infections

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fred D Lublin, MD

Role: PRINCIPAL_INVESTIGATOR

Mt Sinai Medical Center, New York, NY

Locations

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Northwest NeuroSpecialists, PLLC

Tucson, Arizona, United States

The Mt. Sinai Medical Center, Department of Neurology

New York, New York, United States

SUNY Health Science Center at Stony Brook, Department of Neurology

Stony Brook, New York, United States

Wake Forest University - School of Medicine

Winston-Salem, North Carolina, United States

Neurology Health Care Service, Fletcher Allen Health Care

Burlington, Vermont, United States

Department of Neurology, Karl-Franzens University

Graz, , Austria

Foothills Hospital

Calgary, Alberta, Canada

London Health Sciences Centre

London, Ontario, Canada

The Ottawa Hospital, General Campus - Neurology Division

Ottawa, Ontario, Canada

CHUM Hospital Notre Dame

Montreal, Quebec, Canada

Fakultni nemocnice Brno-Bohunice

Brno, , Czechia

St. Anna's Teaching Hospital

Brno, , Czechia

Všeobecná fakultní nemocnice

Prague, , Czechia

Department of Neurology, Motol Teaching Hospital

Prague, , Czechia

Medizinische Einrichtungen der Heinrich Heine Universitat, Neurologische Klinik

Düsseldorf, , Germany

HELIOS Klinikum Erfurt GmbH, Klinik und Poliklinik fur Neurologie

Erfurt, , Germany

Klinikum der Justus-Liebig-Universitat, Zentrum fur Neurologie und Neurochirurgie

Giessen, , Germany

Universitatsklinikum Munster, Klinik und Poliklinik fur Neurologie

Münster, , Germany

Klinikum Osnabrück GmbH

Osnabrück, , Germany

Universitatsklinikum Ulm, Poliklinik fur Neurologie

Ulm, , Germany

Klinijum der Universitat Wurzburg, Neurologische Klinik und Poliklinik

Würzburg, , Germany

Henry Dunant Hospital

Athens, , Greece

Szent Imre Korhaz Neurologia

Budapest, , Hungary

Uzsoki Street Hospital

Budapest, , Hungary

Jahn Ferenc Delpesti Teaching Hospital

Budapest, , Hungary

Szeged University of Science

Szeged, , Hungary

Lady Davis Carmel Medical Center

Haifa, , Israel

Katedra I Klinika Neurologii; Slaskiej Akademii Medycznej, Samodzielny Publiczny Centralny Szpital Kliniczny

Katowice-Ligota, , Poland

Katedra I Klinika Neurologii, Univerytetu Medycznego w Lodzi

Lodz, , Poland

Katedra I Klinika Neurologii

Lublin, , Poland

Klinika Neurologiczna, Wojskowy Instut Medyczny

Warsaw, , Poland

Fakultna menocnica Bratislava

Bratislava, , Slovakia

Dererova nemocnica s Poliklinikou Nerologicka Klinika

Bratislava, , Slovakia

Lasarette Neurologiavdeling

Lund, , Sweden

Karilinska Sjukhuset

Stockholm, , Sweden

University Hospital, Queens Medical Centre

Nottingham, , United Kingdom

Countries

United States; Austria; Canada; Czechia; Germany; Greece; Hungary; Israel; Poland; Slovakia; Sweden; United Kingdom

References

Fazekas F, Lublin FD, Li D, Freedman MS, Hartung HP, Rieckmann P, Sorensen PS, Maas-Enriquez M, Sommerauer B, Hanna K; PRIVIG Study Group; UBC MS/MRI Research Group. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial. Neurology. 2008 Jul 22;71(4):265-71. doi: 10.1212/01.wnl.0000318281.98220.6f.

Reference Type: RESULT

PMID: 18645164 (View on PubMed)

Other Identifiers

100434

Identifier Type: -

Identifier Source: org_study_id