Alemtuzumab in Autoimmune Inflammatory Neurodegeneration: Mechanisms of Action and Neuroprotective Potential (ALAIN01)

University Hospital Muenster

Status and phase: Completed; Phase 4

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Drug: Alemtuzumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02419378

U1111-1156-6489 (Other Identifier)

UKM12_0026

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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]).

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

alemtuzumab

Experimental group

Description:

Administration of 2 courses of alemtuzumab at an interval of 1 year. Course 1: Intravenous infusion of 12 mg alemtuzumab per day on 5 consecutive days. Course 2: Intravenous infusion of 12 mg alemtuzumab per day on 3 consecutive days.

Treatment:

Drug: Alemtuzumab