Immune Globulin Intravenous (IGIV) To Treat Relapsing, Remitting Multiple Sclerosis - Full Text View

Sponsor:	Talecris Biotherapeutics
Information provided by:	Talecris Biotherapeutics
ClinicalTrials.gov Identifier:	NCT00220779

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%, USP	Phase II

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:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Albumins, human Immunoglobulins Aluminum Globulin, Immune

U.S. FDA Resources

Further study details as provided by Talecris Biotherapeutics:

Primary Outcome Measures:

MS relapse free [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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%, 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 IgA deficiency or known antibodies to IgA
Conditions whose symptoms and effects could alter protein catabolism and/or 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

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

Show 37 Study Locations

Sponsors and Collaborators

Talecris Biotherapeutics

Investigators

Principal Investigator:

Fred D Lublin, MD

Mt Sinai Medical Center, New York, NY

More Information

Additional Information:

Synopsis of Study Results This link exits the ClinicalTrials.gov site

FDA Approved Product Labeling Information - Plasbumin®-25 (Low Aluminum) This link exits the ClinicalTrials.gov site

FDA Product Product Labeling Information - Gamunex® This link exits the ClinicalTrials.gov site

FDA Product Approval - Gamunex® This link exits the ClinicalTrials.gov site

Publications:

Fazekas F, Lublin FD, Li D, Freedman MS, Hartung HP, Rieckmann P, Sørensen 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.

Responsible Party:	Gerald Klein, MD, Chief Medical Officer, Vice President of Medical and Clinical Affairs, Talecris Biotherapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00220779 History of Changes
Other Study ID Numbers:	100434
Study First Received:	September 13, 2005
Last Updated:	August 21, 2009
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
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012