LIME Study (LFB IVIg MMN Efficacy Study)

NCT ID: NCT01951924

Last Updated: 2016-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2016-07-31

Brief Summary

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.

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.

Conditions

Motor Neuron Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

Interventions

Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

Laboratoire français de Fractionnement et de Biotechnologies

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Marc LEGER, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital de la Pitié Salpêtrière - Paris 75013

Locations

CHU de Bordeaux -Hôpital Haut-Lévêque

Bordeaux, , France

CHU Créteil - Groupe Hospitalier Henri Mondor

Créteil, , France

CHRU Lille - Hôpital Roger Salengro

Lille, , France

CHU de Lyon - Hôpital Pierre Wertheimer

Lyon, , France

CHU de Marseille - Hôpital de La Timone

Marseille, , France

CHU de Nice - Hôpital l'Archet

Nice, , France

CHU Paris - Hôpital Pitié Salpétrière

Paris, , France

CHU de Saint Etienne - Hôpital Nord

Saint-Etienne, , France

Università di Genova - Ospedale San Martino

Genova, , Italy

IRCCS Istituto Clinico Humanitas

Milan, , Italy

Università Cattolica del Sacro Cuore

Roma, , Italy

Azienda Ospedaliero Universitaria San Giovanni Battista

Turin, , Italy

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

France; Italy; Spain; United Kingdom

Other Identifiers

I10E-0901

Identifier Type: -

Identifier Source: org_study_id