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

March 28, 2016 updated by: Grifols Therapeutics LLC

Randomized, Double-Blind, Placebo-Controlled Study to Compare the Effects of Different Dose Regimens of IGIV Chromatography (IGIV-C), 10% Treatment on Relapses in Patients With Relapsing Remitting Multiple Sclerosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

128

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8010
        • Department of Neurology, Karl-Franzens University
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Foothills Hospital
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Centre
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital, General Campus - Neurology Division
    • Quebec
      • Montreal, Quebec, Canada, H2L4M1
        • Chum Hospital Notre Dame
  • Czech Republic
      • Brno, Czech Republic, 63900
        • Fakultni nemocnice Brno-Bohunice
      • Brno, Czech Republic, 65691
        • St. Anna's Teaching Hospital
      • Prague, Czech Republic, 15600
        • Department of Neurology, Motol Teaching Hospital
      • Prague 2, Czech Republic, 12808
        • Vseobecna Fakultni Nemocnice
  • Germany
      • Dusseldorf, Germany, 40225
        • Medizinische Einrichtungen der Heinrich Heine Universitat, Neurologische Klinik
      • Erfurt, Germany, 99089
        • HELIOS Klinikum Erfurt GmbH, Klinik und Poliklinik fur Neurologie
      • Giessen, Germany
        • Klinikum der Justus-Liebig-Universitat, Zentrum fur Neurologie und Neurochirurgie
      • Munster, Germany, 48149
        • Universitätsklinikum Münster, Klinik und Poliklinik für Neurologie
      • Osnabrück, Germany, 49076
        • Klinikum Osnabrück GmbH
      • Ulm, Germany, 89075
        • Universitatsklinikum Ulm, Poliklinik fur Neurologie
      • Wurzburg, Germany
        • Klinijum der Universitat Wurzburg, Neurologische Klinik und Poliklinik
  • Greece
      • Athens, Greece, 11526
        • Henry Dunant hospital
  • Hungary
      • Budapest, Hungary, 115
        • Szent Imre Korhaz Neurologia
      • Budapest, Hungary, H-1145
        • Uzsoki Street Hospital
      • Budapest, Hungary, H-1204
        • Jahn Ferenc Delpesti Teaching Hospital
      • Szeged, Hungary, H-5720
        • Szeged University of Science
  • Israel
      • Haifa, Israel, 34362
        • Lady Davis Carmel Medical Center
  • Poland
      • Katowice-Ligota, Poland, 40-752
        • Katedra I Klinika Neurologii; Slaskiej Akademii Medycznej, Samodzielny Publiczny Centralny Szpital Kliniczny
      • Lodz, Poland, 90-153
        • Katedra I Klinika Neurologii, Univerytetu Medycznego w Lodzi
      • Lublin, Poland, 20-954
        • Katedra i Klinika Neurologii
      • Warsaw, Poland, 00-909
        • Klinika Neurologiczna, Wojskowy Instut Medyczny
  • Slovakia
      • Bratislava 2, Slovakia, 83-305
        • Fakultna menocnica Bratislava
      • Bratislava 2, Slovakia, 833 05
        • Dererova nemocnica s Poliklinikou Nerologicka Klinika
  • Sweden
      • Lund, Sweden
        • Lasarette Neurologiavdeling
      • Stockholm, Sweden
        • Karilinska Sjukhuset
  • United Kingdom
      • Nottingham, United Kingdom, NG7 2UH
        • University Hospital, Queens Medical Centre
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
      • Tucson, Arizona, United States, 85741-3537
        • Northwest NeuroSpecialists, PLLC
    • New York
      • New York, New York, United States, 10029
        • The Mt. Sinai Medical Center, Department of Neurology
      • Stony Brook, New York, United States, 11794-8121
        • SUNY Health Science Center at Stony Brook, Department of Neurology
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University - School of Medicine
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Neurology Health Care Service, Fletcher Allen Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
IGIV-C 0.2 g/kg bw/infusion (2 ml/kg bw)
Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified
Other 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
Experimental: Group 2
IGIV-C 0.4 g/kg bw/infusion (4 ml/kg bw)
Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified
Other 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
Placebo Comparator: Group 3
placebo (0.1% albumin) 4 ml/kg bw/infusion
Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Relapse Free Subjects (no Relapse)
Time Frame: 12 months
A relapse was defined for the purposes of this study as the appearance or reappearance of one or more neurological symptoms or worsening of an old symptom attributed to multiple sclerosis (MS) persisting for at least 48 hours and immediately preceded by a relatively stable or improving neurological state of at least 30 days.
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI)
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grifols Therapeutics LLC

Investigators

  • Principal Investigator: Fred D Lublin, MD, Mt Sinai Medical Center, New York, NY

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (Actual)

February 1, 2005

Study Completion (Actual)

February 1, 2005

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

April 27, 2016

Last Update Submitted That Met QC Criteria

March 28, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 100434

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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