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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00220779
First received: September 13, 2005
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified
Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • Percentage of Relapse Free Subjects (no Relapse) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 128
Study Start Date: December 2002
Study Completion Date: February 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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/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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00220779

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

Publications:
Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT00220779     History of Changes
Other Study ID Numbers: 100434
Study First Received: September 13, 2005
Results First Received: September 24, 2009
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration
Greece: National Organization of Medicines
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Hungary: National Institute of Pharmacy
Czech Republic: State Institute for Drug Control
Austria: Federal Ministry for Health and Women
Canada: Health Canada
Sweden: Medical Products Agency
Israel: Israeli Health Ministry Pharmaceutical Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Slovakia: State Institute for Drug Control

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Albunex
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Contrast Media
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 28, 2014