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

Condition(s) targeted: Multiple Sclerosis, Relapsing-Remitting

Intervention: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified (Drug); Albumin (Human) 25%, United States Pharmacopeia (USP) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Grifols Therapeutics Inc.

Official(s) and/or principal investigator(s):
Fred D Lublin, MD, Principal Investigator, Affiliation: Mt Sinai Medical Center, New York, NY

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.

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

Primary outcome: Percentage of Relapse Free Subjects (no Relapse)

Secondary outcome: Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI)

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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

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

Department of Neurology, Karl-Franzens University, Graz 8010, Austria

Fakultni nemocnice Brno-Bohunice, Brno 63900, Czech Republic

St. Anna's Teaching Hospital, Brno 65691, Czech Republic

Všeobecná fakultní nemocnice, Prague 2 12808, Czech Republic

Department of Neurology, Motol Teaching Hospital, Prague 15600, Czech Republic

Medizinische Einrichtungen der Heinrich Heine Universitat, Neurologische Klinik, Dusseldorf 40225, Germany

HELIOS Klinikum Erfurt GmbH, Klinik und Poliklinik fur Neurologie, Erfurt 99089, Germany

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

Universitatsklinikum Munster, Klinik und Poliklinik fur Neurologie, Munster 48149, Germany

Klinikum Osnabrück GmbH, Osnabrück 49076, Germany

Universitatsklinikum Ulm, Poliklinik fur Neurologie, Ulm 89075, Germany

Klinijum der Universitat Wurzburg, Neurologische Klinik und Poliklinik, Wurzburg, Germany

Henry Dunant Hospital, Athens 11526, Greece

Jahn Ferenc Delpesti Teaching Hospital, Budapest H-1204, Hungary

Szent Imre Korhaz Neurologia, Budapest 115, Hungary

Uzsoki Street Hospital, Budapest H-1145, Hungary

Szeged University of Science, Szeged H-5720, Hungary

Lady Davis Carmel Medical Center, Haifa 34362, Israel

Katedra I Klinika Neurologii; Slaskiej Akademii Medycznej, Samodzielny Publiczny Centralny Szpital Kliniczny, Katowice-Ligota 40-752, Poland

Katedra I Klinika Neurologii, Univerytetu Medycznego w Lodzi, Lodz 90-153, Poland

Katedra I Klinika Neurologii, Lublin 20-954, Poland

Klinika Neurologiczna, Wojskowy Instut Medyczny, Warsaw 00-909, Poland

Dererova nemocnica s Poliklinikou Nerologicka Klinika, Bratislava 2 833 05, Slovakia

Fakultna menocnica Bratislava, Bratislava 2 83-305, Slovakia

Lasarette Neurologiavdeling, Lund, Sweden

Karilinska Sjukhuset, Stockholm, Sweden

University Hospital, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom

Foothills Hospital, Calgary, Alberta T2N 2T9, Canada

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, United States

Northwest NeuroSpecialists, PLLC, Tucson, Arizona 85741-3537, United States

The Mt. Sinai Medical Center, Department of Neurology, New York, New York 10029, United States

SUNY Health Science Center at Stony Brook, Department of Neurology, Stony Brook, New York 11794-8121, United States

Wake Forest University - School of Medicine, Winston-Salem, North Carolina 27157, United States

London Health Sciences Centre, London, Ontario N6A 5A5, Canada

The Ottawa Hospital, General Campus - Neurology Division, Ottawa, Ontario K1H 8L6, Canada

CHUM Hospital Notre Dame, Montreal, Quebec H2L4M1, Canada

Neurology Health Care Service, Fletcher Allen Health Care, Burlington, Vermont 05401, United States

Starting date: December 2002
Last updated: March 6, 2014