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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— PRIVIG  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00220779
• Other study ID #: 100434
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: March 6, 2014
• Start date: December 2002
• Est. completion date: February 2005

Study information

• Verified date: March 2014
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGreece: National Organization of MedicinesGermany: Federal Institute for Drugs and Medical DevicesPoland: Ministry of HealthHungary: National Institute of PharmacyCzech Republic: State Institute for Drug ControlAustria: Federal Ministry for Health and WomenCanada: Health CanadaSweden: Medical Products AgencyIsrael: Israeli Health Ministry Pharmaceutical AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: February 2005
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified

• Albumin (Human) 25%, United States Pharmacopeia (USP)

Locations

Country	Name	City	State
Austria	Department of Neurology, Karl-Franzens University	Graz
Canada	Foothills Hospital	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	CHUM Hospital Notre Dame	Montreal	Quebec
Canada	The Ottawa Hospital, General Campus - Neurology Division	Ottawa	Ontario
Czech Republic	Fakultni nemocnice Brno-Bohunice	Brno
Czech Republic	St. Anna's Teaching Hospital	Brno
Czech Republic	Department of Neurology, Motol Teaching Hospital	Prague
Czech Republic	Všeobecná fakultní nemocnice	Prague 2
Germany	Medizinische Einrichtungen der Heinrich Heine Universitat, Neurologische Klinik	Dusseldorf
Germany	HELIOS Klinikum Erfurt GmbH, Klinik und Poliklinik fur Neurologie	Erfurt
Germany	Klinikum der Justus-Liebig-Universitat, Zentrum fur Neurologie und Neurochirurgie	Giessen
Germany	Universitatsklinikum Munster, Klinik und Poliklinik fur Neurologie	Munster
Germany	Klinikum Osnabrück GmbH	Osnabrück
Germany	Universitatsklinikum Ulm, Poliklinik fur Neurologie	Ulm
Germany	Klinijum der Universitat Wurzburg, Neurologische Klinik und Poliklinik	Wurzburg
Greece	Henry Dunant Hospital	Athens
Hungary	Jahn Ferenc Delpesti Teaching Hospital	Budapest
Hungary	Szent Imre Korhaz Neurologia	Budapest
Hungary	Uzsoki Street Hospital	Budapest
Hungary	Szeged University of Science	Szeged
Israel	Lady Davis Carmel Medical Center	Haifa
Poland	Katedra I Klinika Neurologii; Slaskiej Akademii Medycznej, Samodzielny Publiczny Centralny Szpital Kliniczny	Katowice-Ligota
Poland	Katedra I Klinika Neurologii, Univerytetu Medycznego w Lodzi	Lodz
Poland	Katedra I Klinika Neurologii	Lublin
Poland	Klinika Neurologiczna, Wojskowy Instut Medyczny	Warsaw
Slovakia	Dererova nemocnica s Poliklinikou Nerologicka Klinika	Bratislava 2
Slovakia	Fakultna menocnica Bratislava	Bratislava 2
Sweden	Lasarette Neurologiavdeling	Lund
Sweden	Karilinska Sjukhuset	Stockholm
United Kingdom	University Hospital, Queens Medical Centre	Nottingham
United States	Neurology Health Care Service, Fletcher Allen Health Care	Burlington	Vermont
United States	The Mt. Sinai Medical Center, Department of Neurology	New York	New York
United States	Barrow Neurological Institute at St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	SUNY Health Science Center at Stony Brook, Department of Neurology	Stony Brook	New York
United States	Northwest NeuroSpecialists, PLLC	Tucson	Arizona
United States	Wake Forest University - School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czech Republic,  Germany,  Greece,  Hungary,  Israel,  Poland,  Slovakia,  Sweden,  United Kingdom, 

References & Publications (1)

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 tria — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Relapse Free Subjects (no Relapse)	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	Yes
Secondary	Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI)		1 year	Yes