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

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 15

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 disease-modifying 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 varizella 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 Lemt

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Absolute and relative change from basline of the following cell-counts in the peripheral blood: <br>a. T cell subsets: <br>- CD4 and CD8 positive T cells: naïve T cells, T effector cells, T memory cells, regulatory T cells; <br>- T-helper subsets: Th1, Th2, Th17 <br>b. B cell subsets:<br>- Recent bone marrow emigrants, mature naïve, memory B cells <br>- Plasma cells <br>c. Natural killer cells: <br>- CD56bright, CD56dim<br>- Natural killer T cells<br>d. Antigen-Presenting cells:<br>- Dendritic cells: CD303+ plasmacytoid, CD11c+ and CD141+ myeloid dendritic cells <br>- Monocytes and macrophages <br>e. Myeloid-derived suppressor cells.<br><br>Times of assessment: <br>12, 24 and 36 months after treatment initiation. If patients provided supplemental consent: additional assessments 6, 18 and 30 months after treatment initiation.

Secondary Outcome Measures