Motor Neuron DiseasePhase 3LIMENCT01951924
LIME Study (LFB IVIg MMN Efficacy Study)
A Phase 3 study testing Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) and Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL) in people with Motor Neuron Disease, run by Laboratoire français de Fractionnement et de Biotechnologies at 18 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Motor Neuron Disease
- What is being tested?
- Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) and Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 18 sitesin 4 countries
- Study dates
- Dec 2013to Jul 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patient aged 18 to 80 years.
- Written informed consent obtained prior to any study-related procedures.
- Diagnosis of definite or probable MMN according to the EFNS/PNS Guideline 2010, First revision made by neuromuscular disease specialists with specific electrodiagnostic expertise.
- 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.
- Covered by national health care insurance system if required by local regulations.
Who cannot join
- Upper motor neuron, bulbar, cranial nerve or significant sensory deficit.
- CSF protein >100 mg/dL (if available and done as part of a previous evaluation).
- 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.
- BMI >= 40 kg/m2.
- Known hypersensitivity to the active substance or to any of the excipients of I10E (glycine and polysorbate 80) or Kiovig(glycine).
- Patient who have been treated with Kiovig shall not have received Kiovig during the last 6 months prior to enrolment.
Show all 21Show fewer
- History of IgA deficiency, except if the absence of anti-IgA antibodies is documented.
- 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.
- History of cardiac insufficiency (New York Heart Association (NYHA) III/IV), uncontrolled cardiac arrythmia, unstable ischemic heart disease, or uncontrolled hypertension.
- History of venous thrombo-embolic disease, myocardial infarction, or cerebrovascular accident.
- Risk factor for blood hyperviscosity such as cryoglobulinemia or haematological malignancy with monoclonal gammopathy.
- Glomerular filtration rate <80 ml/min/1.73m2 measured according to the Modified Diet in Renal Disease (MDRD) calculation.
- Serum levels of AST, ALT >2 times upper limit of normal range.
- 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).
- Administration of another investigational product within the last month prior to inclusion.
- Plasma exchange, blood products or derivatives administered with the last 3 months prior to screening.
- 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).
- Any serious medical condition that would interfere with the clinical assessment of I10E or prevent the patient from complying with the protocol requirements.
- Anticipated poor compliance of patient with study procedures during the 12 month duration of the study.
- Drug or alcohol abuse.
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
France8 sites
CHU de Bordeaux -Hôpital Haut-Lévêque
Bordeaux, 33604
CHU Créteil - Groupe Hospitalier Henri Mondor
Créteil, 94010
CHRU Lille - Hôpital Roger Salengro
Lille, 59037
CHU de Lyon - Hôpital Pierre Wertheimer
Lyon, 69677
CHU de Marseille - Hôpital de La Timone
Marseille, 13385
CHU de Nice - Hôpital l'Archet
Nice, 06202
CHU Paris - Hôpital Pitié Salpétrière
Paris, 75651
CHU de Saint Etienne - Hôpital Nord
Saint-Etienne, 42055
Italy4 sites
Università di Genova - Ospedale San Martino
Genova, 16132
IRCCS Istituto Clinico Humanitas
Milan, 20089
Università Cattolica del Sacro Cuore
Roma, 00168
Azienda Ospedaliero Universitaria San Giovanni Battista
Turin, 10126
Spain4 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, 15706
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitari i Politècnic La Fe
Valencia, 46026
United Kingdom2 sites
Queen Elizabeth Hospital
Birmingham, B15 2WB
Southampton General Hospital
Southampton, SO16 6YD
About this study
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
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.
Read the 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
- Being tested
- Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL), Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)
- Keywords
- Multifocal Motor Neuropathy
- Medical subject headings
- Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL)Drug
Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)Drug
| Study group | Role | What they receive |
|---|---|---|
| Group A: I10E then Kiovig® | Experimental | 1 g/kg for 1-3 days up to 2 g/kg for 2-5 days every 4 to 8 weeks (±7 days) Receives: Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL); Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL) |
| Group B : Kiovig® then I10E | Experimental | 1 g/kg for 1-3 days up to 2 g/kg for 2-5 days every 4 to 8 weeks (±7 days) Receives: Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL); Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change between I10E and Kiovig® in the original MMRC 10 sum score described by Cats 2008
Measured: at 6 months and 1 year
Secondary outcomes (6)
Change between I10E and Kiovig® in: MMRC 10 new sum score (10 slightly different muscles on both sides)
Measured: at 6 months and 1 year
AEs observed and reported TAAEs (temporally associated AE) beginning at infusion or within 72H after infusion
Measured: from 49 to 56 weeks
Change between I10E and Kiovig® in : Rasch built MMRC sum score (Cats 2008)
Measured: at 6 months and 1 year
Change between I10E and Kiovig® in : INCAT: upper and lower limbs
Measured: at 6 months and 1 year
Change between I10E and Kiovig®: Grip strength
Measured: at 6 months and 1 year
Change between I10E and Kiovig® in: MMRC 14 sum score
Measured: at 6 months and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2013 (estimated)
- Study startDec 2013
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Motor Neuron DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratoire français de Fractionnement et de Biotechnologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- TFS Trial Form Support
- Responsible party
- Sponsor
- Investigators
- Jean-Marc LEGER, MD, Principal investigator, Hôpital de la Pitié Salpêtrière - Paris 75013
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951924
- Sponsor's protocol ID
- I10E-0901
- Acronym
- LIME
- Status last verified
- Jul 2016
- First submitted
- 20 Sep 2013
- Last updated
- 19 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01951924
- Acronym / sponsor ID
- LIME / I10E-0901
- Conditions
- Motor Neuron Disease
- Keywords
- Multifocal Motor Neuropathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Laboratoire français de Fractionnement et de BiotechnologiesIndustry (pharma, biotech, devices)
- Collaborators
- TFS Trial Form Support
- Study start
- Dec 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 27 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: I10E then Kiovig® | Experimental | Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL), Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)1 g/kg for 1-3 days up to 2 g/kg for 2-5 days every 4 to 8 weeks (±7 days) |
| Group B : Kiovig® then I10E | Experimental | Drug: Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL), Drug: Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL)1 g/kg for 1-3 days up to 2 g/kg for 2-5 days every 4 to 8 weeks (±7 days) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patient aged 18 to 80 years.
- Written informed consent obtained prior to any study-related procedures.
- Diagnosis of definite or probable MMN according to the EFNS/PNS Guideline 2010, First revision made by neuromuscular disease specialists with specific electrodiagnostic expertise.
- 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.
- Covered by national health care insurance system if required by local regulations.
Key exclusion criteria (21 listed)
- Upper motor neuron, bulbar, cranial nerve or significant sensory deficit.
- CSF protein >100 mg/dL (if available and done as part of a previous evaluation).
- 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.
- BMI >= 40 kg/m2.
- Known hypersensitivity to the active substance or to any of the excipients of I10E (glycine and polysorbate 80) or Kiovig(glycine).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) | Drug | Group A: I10E then Kiovig®, Group B : Kiovig® then I10E |
| Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL) | Drug | Group A: I10E then Kiovig®, Group B : Kiovig® then I10E |
Primary outcome
Change between I10E and Kiovig® in the original MMRC 10 sum score described by Cats 2008
Time frame: at 6 months and 1 year
6 secondary outcomes
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
AEs observed and reported TAAEs (temporally associated AE) beginning at infusion or within 72H after infusion
Time frame: from 49 to 56 weeks
Change between I10E and Kiovig® in : Rasch built MMRC sum score (Cats 2008)
Time frame: at 6 months and 1 year
Change between I10E and Kiovig® in : INCAT: upper and lower limbs
Time frame: at 6 months and 1 year
Change between I10E and Kiovig®: Grip strength
Time frame: at 6 months and 1 year
Change between I10E and Kiovig® in: MMRC 14 sum score
Time frame: at 6 months and 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Marc LEGER, MD principal investigator
Hôpital de la Pitié Salpêtrière - Paris 75013
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Biological : I10E (Human normal Immunoglobulin for intravenous administration 100mg/mL) and Biological: Kiovig® (Human normal Immunoglobulin for intravenous administration 100mg/mL) in people with Motor Neuron Disease, run by Laboratoire français de Fractionnement et de Biotechnologies at 18 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France, Italy, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change between I10E and Kiovig® in the original MMRC 10 sum score described by Cats 2008 (time frame: at 6 months and 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2016; AzTrials last refreshed its copy on 27 Oct 2026.