LIME Study (LFB IVIG MMN Efficacy Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Laboratoire français de Fractionnement et de Biotechnologies
Sponsor:
Collaborator:
TFS Trial Form Support
Information provided by (Responsible Party):
Laboratoire français de Fractionnement et de Biotechnologies
ClinicalTrials.gov Identifier:
NCT01951924
First received: September 20, 2013
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

The aim of this study is to evaluate the efficacy and safety of I10E (LFB 10% ready-to-use liquid human intravenous immunoglobulin) compared to Kiovig® for the maintenance treatment of MMN in a randomized, double-blind, active comparator-controlled, cross-over trial.


Condition Intervention Phase
Motor Neuron Disease
Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL)
Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A European, Randomised, Double-blind, Active Comparator Controlled, Cross-over, Efficacy and Safety Study of a New 10% Ready To-use Liquid Human Intravenous Immunoglobulin (I10E) Versus Kiovig® in Patients With Multifocal Motor Neuropathy

Resource links provided by NLM:


Further study details as provided by Laboratoire français de Fractionnement et de Biotechnologies:

Primary Outcome Measures:
  • Change between I10E and Kiovig® in the original MMRC 10 sum score described by Cats 2008 [ Time Frame: between 3 and 6 months and between 9 and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change between I10E and Kiovig® in: MMRC 10 new sum score (10 slightly different muscles on both sides) [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]
  • AEs observed and reported TAAEs (temporally associated AE) beginning at infusion or within 72H after infusion [ Time Frame: from 49 to 56 weeks ] [ Designated as safety issue: Yes ]
  • Change between I10E and Kiovig® in : Rash built MMRC sum score (CATs 2008) [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]
  • Change between I10E and Kiovig® in : INCAT: upper and lower limbs [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]
  • Change between I10E and Kiovig®: Grip strengh [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]
  • Change between I10E and Kiovig® in: MMRC 14 sum score [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: I10E then Kiovig
1 g/kg for 1-3 days every 4 weeks ±7 days Up to 2 g/kg for 2-5 days every 4 weeks ±7 days to 8 weeks ±7 days
Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)
Experimental: Group B : Kiovig then I10E
1 g/kg for 1-3 days every 4 weeks ±7 days Up to 2 g/kg for 2-5 days every 4 weeks ±7 days to 8 weeks ±7 days
Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Detailed Description:

Multifocal motor neuropathy (MMN) is a chronic acquired, probably autoimmune, demyelinating, motor neuropathy. It is a rare disease, variable in its clinical features. The disease course is usually steadily progressive.

Intravenous immunoglobulin (IVIG) is the standard and the first line treatment for MMN. The Cochrane review of four randomized placebo-controlled studies showed a significant clinical improvement in muscle strength from IVIG in 78% of patients with MMN versus 4% with placebo but a non-significant improvement in disability (39% versus 11%) (van Schaik IN, 2005). However, IVIG treatment does not prevent a mild gradual decline in muscle strength which is probably due to ongoing axonal degeneration. In addition to its efficacy, IVIG is also a safe treatment with a positive benefit-risk ratio in MMN.

Muscle strength measured with the Modified Medical Research Council (MMRC 10) sum score as described in the study of Cats (Cats EA, 2008) including 20 movements i.e. 10 muscle groups of the upper and lower limbs on each side was selected as the primary endpoint. Other parameters of muscle strength such as measurement of grip strength by dynamometer - and functional disability will also be evaluated to reinforce the robustness of the study and substantiate the efficacy of I10E in MMN patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patient aged 18 to 80 years.
  2. Written informed consent obtained prior to any study-related procedures.
  3. Diagnosis of definite or probable MMN according to the EFNS/PNS Guideline 2010, First revision made by neuromuscular disease specialists with specific electrodiagnostic expertise.
  4. Patients treated with a stable maintenance dose (without any change in doses > or < 15% ) of any brand of IVIG (Kiovig excluded) at 1 g/kg body weight every 4-week intervals up to 2 g/kg body weight every 4-week to 8-week intervals according to the EFNS/PNS Guideline 2010, First revision for at least 3 months prior to enrolment.
  5. Covered by national health care insurance system if required by local regulations.

Exclusion Criteria:

  1. Upper motor neuron, bulbar, cranial nerve or significant sensory deficit.
  2. CSF protein >100 mg/dL (if available and done as part of a previous evaluation).
  3. Any disease that may cause neuropathy or may interfere with outcome assessments, such as diabetes, vasculitis, or systemic lupus erythematosus.
  4. BMI >= 40 kg/m2.
  5. Known hypersensitivity to the active substance or to any of the excipients of I10E (glycine and polysorbate 80) or Kiovig(glycine).
  6. History of Kiovig use.
  7. History of IgA deficiency, except if the absence of anti-IgA antibodies is documented.
  8. Patient infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
  9. Protein-losing enteropathy characterised by serum protein levels <60 g/l and serum albumin levels <30 g/l or nephrotic syndrome characterised by proteinuria >=3.5 g/24 hours, serum protein levels <60 g/l and serum albumin levels <30 g/l.
  10. History of cardiac insufficiency (New York Heart Association (NYHA) III/IV) or uncontrolled severe hypertension.
  11. History of thrombotic episodes (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident).
  12. Glomerular filtration rate <80 ml/min/1.73m2 measured according to the Modified Diet in Renal Disease (MDRD) calculation.
  13. Serum levels of AST, ALT and/or ALP >2 times upper limit of normal range.
  14. Patient treated with immunomodulator/immunosuppressor (e.g. cyclophosphamide, cyclosporine or interferon), except use at the same dose of: methotrexate, mycophenolate mofetil, or azathioprine for at least 6 months before the inclusion visit.
  15. Treatment with an anti-CD20 antibody within the 12 previous months.
  16. Administration of another investigational product within the last month prior to inclusion.
  17. Exposure to blood products or derivatives other than commercial IgG, within 3 months prior to inclusion.
  18. Positive results of pregnancy blood test or breast-feeding woman or woman of childbearing potential without effective contraception for the duration of the study.
  19. Any serious medical condition that would interfere with the clinical assessment of I10E or prevent the patient from complying with the protocol requirements.
  20. Anticipated poor compliance of patient with study procedures during the 12 month duration of the study.
  21. Drug or alcohol abuse.
  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: NCT01951924

Contacts
Contact: Alain SADOUN, MD +33 (0) 1 69 82 56 12 sadoun@lfb.fr
Contact: Mazen ELZAABI, MD elzaabi@lfb.fr

Locations
France
CHU de Bordeaux -Hôpital Haut-Lévêque Not yet recruiting
Bordeaux, France, 33604
Principal Investigator: Gwendal Le Masson, MD, PhD         
CHU Créteil - Groupe Hospitalier Henri Mondor Not yet recruiting
Creteil, France, 94010
Principal Investigator: Alain Creange, MD, PhD         
CHRU Lille - Hôpital Roger Salengro Recruiting
Lille, France, 59037
Principal Investigator: Arnaud LACOUR, MD         
CHU de Lyon - Hôpital Pierre Wertheimer Recruiting
Lyon, France, 69677
Principal Investigator: Christophe VIAL, MD         
CHU de Marseille - Hôpital de La Timone Not yet recruiting
Marseille, France, 13385
Sub-Investigator: Jean Pouget, MD, PhD         
CHU de Nice - Hôpital l'Archet Recruiting
Nice, France, 06202
Principal Investigator: Claude DESNUELLE, MD, PhD         
CHU de Saint Etienne - Hôpital Nord Recruiting
Saint Etienne, France, 42055
Principal Investigator: Jean Christophe Antoine, MD, PhD         
Italy
IRCCS Istituto Clinico Humanitas Not yet recruiting
Milan, Italy, 20089
Principal Investigator: Eduardo NOBILE-ORAZIO, MD, PhD         
Azienda Ospedaliero Universitaria San Giovanni Battista Not yet recruiting
Turin, Italy, 10126
Principal Investigator: Dario COCITO, MD         
Spain
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08041
Principal Investigator: Ricardo ROJAS-GARCIA, MD         
Hospital Universitari i Politècnic La Fe Not yet recruiting
Valencia, Spain, 46026
Principal Investigator: Teresa Sevilla, MD         
United Kingdom
Queen Elizabeth Hospital Not yet recruiting
Birmingham, United Kingdom, B15 2WB
Principal Investigator: Yusuf RAJABALLY, MD         
Royal Preston Hospital Not yet recruiting
Preston, United Kingdom, PR2 9HT
Principal Investigator: John Nixon, MD         
Southampton General Hospital Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Principal Investigator: Haider Katifi, MD         
Sponsors and Collaborators
Laboratoire français de Fractionnement et de Biotechnologies
TFS Trial Form Support
Investigators
Principal Investigator: Jean-Marc LEGER, MD Hôpital de la Pitié Salpêtrière - Paris 75013
  More Information

No publications provided

Responsible Party: Laboratoire français de Fractionnement et de Biotechnologies
ClinicalTrials.gov Identifier: NCT01951924     History of Changes
Other Study ID Numbers: I10E-0901
Study First Received: September 20, 2013
Last Updated: September 24, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Italy: Agenzia Italiana del Farmaco
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Laboratoire français de Fractionnement et de Biotechnologies:
Multifocal Motor Neuropathy

Additional relevant MeSH terms:
Motor Neuron Disease
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Immunoglobulins
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014