LIME Study (LFB IVIg MMN Efficacy Study)

Motor Neuron Disease Clinical Trial

— LIME  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951924
• Other study ID #: I10E-0901
• Status: Completed
• Phase: Phase 3
• First received: September 20, 2013
• Last updated: July 18, 2016
• Start date: December 2013
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: Laboratoire français de Fractionnement et de Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéFrance: Committee for the Protection of PersonnesItaly: Agenzia Italiana del FarmacoSpain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación ClínicaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeItaly: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Motor Neuron Disease

Intervention

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

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

Locations

Country	Name	City	State
France	CHU de Bordeaux -Hôpital Haut-Lévêque	Bordeaux
France	CHU Créteil - Groupe Hospitalier Henri Mondor	Creteil
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
Italy	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
Spain	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	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Southampton General Hospital	Southampton

Sponsors (2)

Lead Sponsor	Collaborator
Laboratoire français de Fractionnement et de Biotechnologies	TFS Trial Form Support

Countries where clinical trial is conducted

France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change between I10E and Kiovig® in the original MMRC 10 sum score described by Cats 2008		at 6 months and 1 year	No
Secondary	Change between I10E and Kiovig® in: MMRC 10 new sum score (10 slightly different muscles on both sides)		at 6 months and 1 year	No
Secondary	AEs observed and reported TAAEs (temporally associated AE) beginning at infusion or within 72H after infusion		from 49 to 56 weeks	Yes
Secondary	Change between I10E and Kiovig® in : Rasch built MMRC sum score (Cats 2008)		at 6 months and 1 year	No
Secondary	Change between I10E and Kiovig® in : INCAT: upper and lower limbs		at 6 months and 1 year	No
Secondary	Change between I10E and Kiovig®: Grip strength		at 6 months and 1 year	No
Secondary	Change between I10E and Kiovig® in: MMRC 14 sum score		at 6 months and 1 year	No