LIME Study (LFB IVIg MMN Efficacy Study) (LIME)

This study has been completed.
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: July 18, 2016
Last verified: July 2016
  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: at 6 months and 1 year ] [ 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 : Rasch 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 strength [ 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 ]

Enrollment: 23
Study Start Date: December 2013
Study Completion Date: July 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: I10E then Kiovig®
1 g/kg for 1-3 days up to 2 g/kg for 2-5 days every 4 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 up to 2 g/kg for 2-5 days every 4 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   (Adult, Senior)
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 within 15% of any brand of IVIg (Kiovig® excluded) at 1 g/kg for 1-3 days up to 2 g/Kg for 2-5 days every 4 to 8 weeks (+/- 7 days), 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 other ongoing disease that may cause neuropathy, such as toxin exposure, dietary difficency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus erythematosus or other connective diseases, infection with HIV, hepatitis B virus (HBV), or hepatitis C (HCV), Lyme disease, multiple myeloma, Waldenström's macroglobulinemia, amyloid, and hereditary neuropathy.
  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. Patient who have been treated with Kiovig shall not have received Kiovig during the last 6 months prior to enrolment.
  7. History of IgA deficiency, except if the absence of anti-IgA antibodies is documented.
  8. 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.
  9. History of cardiac insufficiency (New York Heart Association (NYHA) III/IV), uncontrolled cardiac arrythmia, unstable ischemic heart disease, or uncontrolled hypertension.
  10. History of venous thrombo-embolic disease, myocardial infarction, or cerebrovascular accident.
  11. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematological malignancy with monoclonal gammopathy.
  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 >2 times upper limit of normal range.
  14. Treatment within 12 months prior to screeening with immunomodulator or immunosuppressant agent (including but not limited to cyclophosphamide, cyclosporine, interferon-a, interferon-b 1a, anti-CD20, alemtuzumab, azathioprine, etanarcept, mycophenolate mofetil, methotrexate, haematopoietic stem cell transplantation).
  15. Administration of another investigational product within the last month prior to inclusion.
  16. Plasma exchange, blood products or derivatives administered with the last 3 months prior to screening.
  17. Woman with positive results of pregnancy test or breast-feeding woman or woman of childbearing potential without an effective contraception.

    Effective contraception are injectible, patch or combined oestro-progestative or progestative contraceptives, Cooper T or levonorgest releasing intra-uterine devices, depot intramuscular medroxyprogesterone, subcutaneous progestative contraceptive implants, condoms or occlusive caps (diaphragm or cervical/vault caps) with spermicide, true abstinence (when this is in line with the preferred and usual lifestyle of the patient).

  18. Any serious medical condition that would interfere with the clinical assessment of I10E or prevent the patient from complying with the protocol requirements.
  19. Anticipated poor compliance of patient with study procedures during the 12 month duration of the study.
  20. 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

Locations
France
CHU de Bordeaux -Hôpital Haut-Lévêque
Bordeaux, France, 33604
CHU Créteil - Groupe Hospitalier Henri Mondor
Creteil, France, 94010
CHRU Lille - Hôpital Roger Salengro
Lille, France, 59037
CHU de Lyon - Hôpital Pierre Wertheimer
Lyon, France, 69677
CHU de Marseille - Hôpital de La Timone
Marseille, France, 13385
CHU de Nice - Hôpital l'Archet
Nice, France, 06202
CHU Paris - Hôpital Pitié Salpétrière
Paris, France, 75651
CHU de Saint Etienne - Hôpital Nord
Saint Etienne, France, 42055
Italy
Università di Genova - Ospedale San Martino
Genova, Italy, 16132
IRCCS Istituto Clinico Humanitas
Milan, Italy, 20089
Università Cattolica del Sacro Cuore
Roma, Italy, 00168
Azienda Ospedaliero Universitaria San Giovanni Battista
Turin, Italy, 10126
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, Spain, 15706
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Universitari i Politècnic La Fe
Valencia, Spain, 46026
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2WB
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
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

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: July 18, 2016
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
Italy: 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
Immunoglobulins, Intravenous
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016