Clinical trial NCT02419378: Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential
Official title: Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2015-04-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Alemtuzumab is the active agent of a drug called Lemtrada®. In the European Union, Lemtrada® is approved for the treatment of a particular form of multiple sclerosis (the so called relapsing remitting form). The excellent efficacy of the drug justifies its administration albeit a high risk of considerable side effects. In this context, so called secondary (occurring after the administration of Lemtrada®) autoimmune diseases are of particular importance. In these diseases the immune system acts against structures of the body itself; the reasons are still unknown. Autoimmune diseases may even occur several years after treatment with Lemtrada®. Therefore, patients who once received the drug need to undergo intensive long term health monitoring.

This study aims to elucidate which mechanisms cause to the positive and negative effects of Lemtrada®.

The study includes patients only, who suffer from multiple sclerosis and are indicated to be treated with Lemtrada®. All patients receive the drug according to the official recommendations.


Eligibility 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 \[diaphragm or cervical cap combined with spermicide\]).

Primary outcomes:
measure: Absolute change from baseline in naïve CD4 positive T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in naïve CD4 positive T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in naïve CD8 positive T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in naïve CD8 positive T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD4 positive T effector cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD4 positive T effector cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD8 positive T effector cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD4 positive T memory cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD4 positive T memory cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD8 positive T memory cell counts peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD8 positive T memory cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD4 positive regulatory T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD4 positive regulatory T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD8 positive regulatory T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD8 positive regulatory T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in Th1 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in Th1 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in Th2 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in Th2 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in Th17 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in Th17 T-helper cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in recent bone marrow emigrant B cell counts peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in recent bone marrow emigrant B cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in mature naïve B cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in mature naïve B cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in memory B cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in memory B cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in plasma cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in plasma cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD56bright natural killer cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD56bright natural killer cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD56dim natural killer cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD56dim natural killer cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in natural killer T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in natural killer T cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD303+ plasmacytoid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD303+ plasmacytoid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD11c+ myeloid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD11c+ myeloid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in CD141+ myeloid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in CD141+ myeloid dendritic cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in monocyte counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in monocyte counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in macrophage counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in macrophage counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute change from baseline in myeloid-derived suppressor cell counts in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative change from baseline in myeloid-derived suppressor cell counts in peripheral blood
timeFrame: 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 outcomes:
measure: Absolute change from baseline in naïve CD4 positive T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in naïve CD4 positive T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in naïve CD8 positive T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in naïve CD8 positive T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD4 positive T effector cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD4 positive T effector cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD8 positive T effector cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD8 positive T effector cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD4 positive T memory cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD4 positive T memory cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD8 positive T memory cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD8 positive T memory cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD4 positive regulatory T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD4 positive regulatory T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD8 positive regulatory T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD8 positive regulatory T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in Th1 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in Th1 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in Th2 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in Th2 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in Th17 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in Th17 T-helper cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in recent bone marrow emigrant B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in recent bone marrow emigrant B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in mature naïve B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in mature naïve B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in memory B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in memory B cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in plasma cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in plasma cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD56bright natural killer cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD56bright natural killer cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD56dim natural killer cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD56dim natural killer cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in natural killer T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in natural killer T cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD303+ plasmacytoid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD303+ plasmacytoid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD11c+ myeloid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD11c+ myeloid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in CD141+ myeloid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in CD141+ myeloid dendritic cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in monocyte counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in monocyte counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in macrophage counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in macrophage counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Absolute change from baseline in myeloid-derived suppressor cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative change from baseline in myeloid-derived suppressor cell counts in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Activation status of cell surface receptors on T cells fom peripheral blood as assessed by flow cytometry
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Activation status of cell surface receptors on T cells from cerebrospinal fluid as assessed by flow cytometry
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Expression of co-inhibitory molecules by T cells from peripheral blood as assessed by flow cytometry
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Expression of co-inhibitory molecules by T cells from cerebrospinal fluid as assessed by flow cytometry
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Effector functions of CD4 and CD8 positive T cells from peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Effector functions of CD4 and CD8 positive T cells from cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Migrational capacity of T cells from peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Migrational capacity of T cells from cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Spectratyping of the T cell repertoire of T cells from peripheral blood concerning the expansion of distinct clones
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Spectratyping of the T cell repertoire of T cells from cerebrospinal fluid concerning the expansion of distinct clones
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Regulatory T-cell function in peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Regulatory T-cell function in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative and absolute change from baseline in the concentration of markers in the cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: 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
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Relative and absolute change from baseline in the concentration of neurotrophic factors in the peripheral blood
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative and absolute change from baseline in the concentration of neurotrophic factors in cerebrospinal fluid
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: 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
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Relative and absolute change from baseline in retinal nerve fiber layer thickness (assessment by optical coherence tomography)
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Data on Adverse Events
timeFrame: Each day when the patient has a consultation with the investigator
Other outcomes:
measure: Number of patients who experienced sustained accumulation of disability (SAD) during the study period
timeFrame: Date of last patient out anticipated about 4 years after study initiation
measure: Time to SAD
timeFrame: At the end of each patient's study participation, i.e. 36 months after treatment initiation
measure: Time to sustained reduction in disability (SRD) based on EDSS scores
timeFrame: At the end of each patient's study participation, i.e. 36 months after treatment initiation
measure: Absolute Number of relapses during the study period
timeFrame: At the end of each patient's study participation, i.e. 36 months after treatment initiation
measure: Number or relapses which occurred during the study period and required corticosteroid therapy
timeFrame: At the end of each patient's study participation, i.e. 36 months after treatment initiation
measure: Proportion of patients who are relapse free at year 3
timeFrame: Date of last patient out anticipated about 4 years after study initiation
measure: Time to first relapse
timeFrame: At the end of each patient's study participation, i.e. 36 months after treatment initiation
measure: Absolute and relative change from baseline in the following functional scores: EDSS, visual functional system score as part of the assessments for EDSS, MSFC and each MSFC component, FSMC and each subscore (mental and physical fatigue)
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 3, 6, 9, 15, 18, 21, 24, 27, 30 and 33 months after treatment initiation.
measure: The proportion of patients who have worsened, remained stable, or improved as indicated by change from Baseline in EDSS scores at the end of the study
timeFrame: Date of last patient out anticipated about 4 years after study initiation
measure: Change from baseline of the following health-related quality of life (HRQoL) measures: FAMS, EQ-5D (total score, Physical Component Summary Measure, Mental Component Summary Measure), SF-36
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 3, 6, 9, 15, 18, 21, 24, 27, 30 and 33 months after treatment initiation.
measure: The proportion of patients who have worsened, remained stable, or improved as indicated by change from Baseline in MSFC scores at the end of the study
timeFrame: Date of last patient out anticipated about 4 years after study initiation
measure: Absolute and relative change from baseline amplitudes [V] and latencies [s] of evoked potentials (visual, somatosensory, magnetic motor evoked)
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Percent change from baseline in magnetic resonance imaging (MRI)-T2 hyperintense lesion volume
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Number of new gadolinium-enhancing lesions on MRI-T1 in comparison to Baseline
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Number of new or enlarging hyperintense lesions measured by T2-weighted MRI in comparison to Baseline
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute and relative change from baseline of IL-21 concentration in blood serum
timeFrame: 12, 24 and 36 months after initiation of investigational treatment. In addition on an optional basis: 6, 18 and 30 months after treatment initiation.
measure: Absolute and relative change from baseline of following parameters assessed in CSF: cell counts, concentration of lactate, protein, and immunoglobulins (IgA, IgG, AgM)
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Qualitative assessment of the change in presence of oligoclonal bands in CSF from baseline
timeFrame: 12, 24 and 36 months after initiation of investigational treatment on an optional basis
measure: Proportion of patients with no multiple sclerosis disease activity (i.e., deterioration in MRI related endpoints, relapse) at the end of the study
timeFrame: Date of last patient out anticipated about 4 years after study initiation
Locations:
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
Study officials:
affiliation: University Hospital Muenster
name: Sven Meuth, Prof. Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruck T, Afzali AM, Lukat KF, Eveslage M, Gross CC, Pfeuffer S, Bittner S, Klotz L, Melzer N, Wiendl H, Meuth SG. ALAIN01--Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential. BMC Neurol. 2016 Mar 10;16:34. doi: 10.1186/s12883-016-0556-9.