Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential

• Register: ClinicalTrials.gov
• Last refreshed on: 8 November 2021
• Main ID: NCT02419378
• Date of registration: 31/03/2015
• Prospective Registration: Yes
• Primary sponsor: University Hospital Muenster
• Public title: Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential ALAIN01
• Scientific title: Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential
• Date of first enrolment: June 2015
• Target sample size: 15
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02419378
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Germany

Contacts

• Name: Sven Meuth, Prof. Dr. Dr.
• Affiliation: University Hospital Muenster

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed informed consent form (ICF)

2. Age 18 to 55 years old (inclusive) as of the date the ICF is signed

3. Diagnosis of MS according to the McDonald criteria 2010 and cranial MRI scan
demonstrating white matter lesions attributable to MS within 10 years before Screening

4. Onset of MS symptoms (as determined by a neurologist, either at present or
retrospectively) within 10 years of the date the ICF is signed

5. EDSS score 0.0 to 5.0 (inclusive) at Screening

6. Patients with (highly) active RRMS disease course indicated to receive alemtuzumab
according to the following conditions (at least 1 out of 3 conditions has to be
fulfilled): 1. =2 MS relapses within 24 months, 2. clinical (=1 relapse) or MRI (new
gadolinium enhancing lesions) disease activity under therapy with other
diseasemodifying therapies, 3. severe relapse with high disease activity (=9 T2
hyperintense Lesions and =1 gadolinium enhancing lesion) on MRI.

7. Completion of all vaccinations required by the applicable immunization guidelines
published by "ständige Impfkommission" (STIKO)

8. History of chickenpox or positive test for antibodies against varicella zoster virus
(VZV)

Exclusion Criteria:

1. Participation in another clinical trial at present or within 4 weeks of study entry.
There may be exceptions at the discretion of the Investigator.

2. Has any progressive form of MS

3. Hypersensitivity to the active substance, or to any of the excipients of Lemtrada®

4. Medical, psychiatric, cognitive, or other conditions that, in the Investigator's
opinion, compromise the patient's ability to understand the patient information, to
give informed consent, to comply with the trial protocol, or to complete the study

5. Any disability acquired from trauma or another illness that could interfere with
evaluation of disability due to MS

6. Major systemic disease or other illness that would, in the opinion of the
Investigator, compromise patient safety or interfere with the interpretation of study
results, e.g., current peptic ulcer disease or other conditions that may predispose to
hemorrhage

7. Known bleeding disorder (e.g,. dysfibrinogenemia, factor IX deficiency, hemophilia,
Von Willebrand's disease, disseminated intravascular coagulation (DIC), fibrinogen
deficiency, or clotting factor deficiency)

8. Significant autoimmune disease including but not limited to immune cytopenias,
rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders,
vasculitis, inflammatory bowel disease, severe psoriasis

9. History of malignancy, except basal skin cell carcinoma

10. Major psychiatric disorder that is not adequately controlled by treatment

11. Epileptic seizures that are not adequately controlled by Treatment

12. Active infection, e.g., deep-tissue infection, that the Investigator considers
sufficiently serious to preclude study participation

13. In the Investigator's opinion, is at high risk for infection (e.g., indwelling
catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration
pneumonia or recurrent urinary tract infection)

14. Seropositivity for human immunodeficiency virus (HIV)

15. Infection with hepatitis C Virus

16. Past or present hepatitis B infection (positive hepatitis B serology)

17. Active infection with human cytomegaly virus (HCMV), Epstein-Barr virus (EBV),
varicella-zoster virus (VZV)

18. Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or
active tuberculosis.

19. Invasive fungal infections in history and at present

20. Cervical cytology other than PAP I or PAP II (Papanicolaou) or cervical high risk
human papillomavirus (HPV) positivity

21. Any other illness or infection (latent or active) that, in the Investigator's opinion,
could be exacerbated by study medication

22. Differential blood count < lower limit of normal (LLN) at Screening

23. Confirmed platelet count < the LLN of the evaluating laboratory at Screening or
documented at <100,000/µL within the past year on a sample without platelet clumping

24. Presence (i.e., above the ULN) of anti-thyroid stimulating hormone receptor antibodies
(anti-TSHR) and anti-thyroid peroxidase antibody (anti-TPO)

25. Any hepatic or renal function value grade 2 or higher at Screening, with the exception
of hyperbilirubinemia due to Gilbert's syndrome. See Table below, drawn from the
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0
(CTCAE), published 28 May 2009.

Hepatic

Bilirubin >1.5 × ULN

SGOT/AST >3.0 × ULN

SGPT/ALT >3.0 × ULN

Alkaline phosphatase >2.5 × ULN

Renal

Creatinine > 1.5 × ULN

26. Vaccination less than 6 weeks prior to treatment with Lemtrada.

27. Treatment with antineoplastic or immunosuppressive drugs within 8 weeks prior to study
inclusion

28. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis

29. Inability to undergo MRI with gadolinium administration

30. Of childbearing potential with a positive serum pregnancy test, pregnant or lactating

31. Female patients of childbearing potential: Unwilling to agree to use a reliable and
acceptable contraceptive method (Pearl index <1) throughout the study period. These
methods include: hormone releasing intrauterine device (IUD), hormonal-based
contraception, surgical sterilization, abstinence, or double-barrier contraception
(condom and occlusive cap [diaphragm or cervical cap combined with spermicide]).



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Relapsing-Remitting

Intervention(s)

Drug: Alemtuzumab

Primary Outcome(s)

Absolute change from baseline in CD141+ myeloid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in Th1 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in naïve CD8 positive T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD11c+ myeloid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in plasma cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD303+ plasmacytoid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in recent bone marrow emigrant B cell counts peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD56bright natural killer cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD4 positive T effector cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in Th17 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in macrophage counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in mature naïve B cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD8 positive regulatory T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD4 positive T effector cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD303+ plasmacytoid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in Th2 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in monocyte counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD11c+ myeloid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in natural killer T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD4 positive T memory cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD4 positive T memory cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in macrophage counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in myeloid-derived suppressor cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in memory B cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD4 positive regulatory T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in naïve CD4 positive T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in natural killer T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD56bright natural killer cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in monocyte counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD56dim natural killer cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in plasma cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD8 positive T memory cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in Th1 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in memory B cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in naïve CD8 positive T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in mature naïve B cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD8 positive regulatory T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in naïve CD4 positive T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in recent bone marrow emigrant B cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD4 positive regulatory T cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD141+ myeloid dendritic cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD56dim natural killer cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD8 positive T effector cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Absolute change from baseline in CD8 positive T memory cell counts peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in Th2 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in myeloid-derived suppressor cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in Th17 T-helper cell counts in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Secondary Outcome(s)

Absolute change from baseline in CD4 positive regulatory T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD11c+ myeloid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD4 positive T memory cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD8 positive T effector cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD303+ plasmacytoid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in monocyte counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD56bright natural killer cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in mature naïve B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in Th1 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Activation status of cell surface receptors on T cells from cerebrospinal fluid as assessed by flow cytometry [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in naïve CD8 positive T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Effector functions of CD4 and CD8 positive T cells from cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD56dim natural killer cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD8 positive T memory cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD141+ myeloid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in myeloid-derived suppressor cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in memory B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative and absolute change from baseline in the concentration of neurotrophic factors in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD56bright natural killer cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in mature naïve B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in myeloid-derived suppressor cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in plasma cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in macrophage counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in recent bone marrow emigrant B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Migrational capacity of T cells from cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Regulatory T-cell function in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative and absolute change from baseline in the concentration of markers in the cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD11c+ myeloid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD141+ myeloid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in plasma cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD4 positive regulatory T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Expression of co-inhibitory molecules by T cells from peripheral blood as assessed by flow cytometry [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in Th1 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Migrational capacity of T cells from peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Spectratyping of the T cell repertoire of T cells from cerebrospinal fluid concerning the expansion of distinct clones [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Percent change from Baseline in the following MRI findings which are defined as markers for neurodegeneration: MRI-T1-measured cerebral volume, MRI-T1-measured number of black holes [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in memory B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in monocyte counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in naïve CD4 positive T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD4 positive T effector cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in CD8 positive regulatory T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in Th17 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Data on Adverse Events [Time Frame: Each day when the patient has a consultation with the investigator]

Relative and absolute change from baseline in neuronal activity, action potential generation and cellular integrity by obtained human CSF supernatant samples using multi-electrode arrays [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative and absolute change from baseline in retinal nerve fiber layer thickness (assessment by optical coherence tomography) [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD8 positive T effector cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in natural killer T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in naïve CD4 positive T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in Th2 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Activation status of cell surface receptors on T cells fom peripheral blood as assessed by flow cytometry [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Regulatory T-cell function in peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Effector functions of CD4 and CD8 positive T cells from peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD4 positive T effector cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD4 positive T memory cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD8 positive T memory cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD8 positive regulatory T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in natural killer T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in recent bone marrow emigrant B cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Absolute change from baseline in Th2 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in CD56dim natural killer cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in macrophage counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in naïve CD8 positive T cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Spectratyping of the T cell repertoire of T cells from peripheral blood concerning the expansion of distinct clones [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Expression of co-inhibitory molecules by T cells from cerebrospinal fluid as assessed by flow cytometry [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative and absolute change from baseline in the concentration of neurotrophic factors in the peripheral blood [Time Frame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.]

Relative change from baseline in CD303+ plasmacytoid dendritic cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Relative change from baseline in Th17 T-helper cell counts in cerebrospinal fluid [Time Frame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis]

Secondary ID(s)

U1111-1156-6489

UKM12_0026

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genzyme, a Sanofi Company