Clinical trial NCT00220779: Immune Globulin Intravenous (IGIV) To Treat Relapsing, Remitting Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Relapse Free Subjects (no Relapse)
timeFrame: 12 months
Secondary outcomes:
measure: Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI)
timeFrame: 1 year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: Northwest NeuroSpecialists, PLLC
state: Arizona
city: New York
country: United States
facility: The Mt. Sinai Medical Center, Department of Neurology
state: New York
city: Stony Brook
country: United States
facility: SUNY Health Science Center at Stony Brook, Department of Neurology
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University - School of Medicine
state: North Carolina
city: Burlington
country: United States
facility: Neurology Health Care Service, Fletcher Allen Health Care
state: Vermont
city: Graz
country: Austria
facility: Department of Neurology, Karl-Franzens University
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus - Neurology Division
state: Ontario
city: Montreal
country: Canada
facility: CHUM Hospital Notre Dame
state: Quebec
city: Brno
country: Czech Republic
facility: Fakultni nemocnice Brno-Bohunice
city: Brno
country: Czech Republic
facility: St. Anna's Teaching Hospital
city: Prague 2
country: Czech Republic
facility: Všeobecná fakultní nemocnice
city: Prague
country: Czech Republic
facility: Department of Neurology, Motol Teaching Hospital
city: Dusseldorf
country: Germany
facility: Medizinische Einrichtungen der Heinrich Heine Universitat, Neurologische Klinik
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt GmbH, Klinik und Poliklinik fur Neurologie
city: Giessen
country: Germany
facility: Klinikum der Justus-Liebig-Universitat, Zentrum fur Neurologie und Neurochirurgie
city: Munster
country: Germany
facility: Universitatsklinikum Munster, Klinik und Poliklinik fur Neurologie
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück GmbH
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm, Poliklinik fur Neurologie
city: Wurzburg
country: Germany
facility: Klinijum der Universitat Wurzburg, Neurologische Klinik und Poliklinik
city: Athens
country: Greece
facility: Henry Dunant Hospital
city: Budapest
country: Hungary
facility: Szent Imre Korhaz Neurologia
city: Budapest
country: Hungary
facility: Uzsoki Street Hospital
city: Budapest
country: Hungary
facility: Jahn Ferenc Delpesti Teaching Hospital
city: Szeged
country: Hungary
facility: Szeged University of Science
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Katowice-Ligota
country: Poland
facility: Katedra I Klinika Neurologii; Slaskiej Akademii Medycznej, Samodzielny Publiczny Centralny Szpital Kliniczny
city: Lodz
country: Poland
facility: Katedra I Klinika Neurologii, Univerytetu Medycznego w Lodzi
city: Lublin
country: Poland
facility: Katedra I Klinika Neurologii
city: Warsaw
country: Poland
facility: Klinika Neurologiczna, Wojskowy Instut Medyczny
city: Bratislava 2
country: Slovakia
facility: Fakultna menocnica Bratislava
city: Bratislava 2
country: Slovakia
facility: Dererova nemocnica s Poliklinikou Nerologicka Klinika
city: Lund
country: Sweden
facility: Lasarette Neurologiavdeling
city: Stockholm
country: Sweden
facility: Karilinska Sjukhuset
city: Nottingham
country: United Kingdom
facility: University Hospital, Queens Medical Centre
Study officials:
affiliation: Mt Sinai Medical Center, New York, NY
name: Fred D Lublin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.