Randomized Autologous heMatopoietic Stem Cell Transplantation Versus Alemtuzumab, Cladribine or Ocrelizumab for RRMS (RAM-MS)

Inclusion Criteria:

1. Age between ≥18 to ≤50, both genders

2. Women of childbearing potential* (WOCBP) and men in a sexual relation with WOCBPmust be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when usedconsistently and correctly.

3. Diagnosis of RRMS using revised McDonald criteria of clinically definite MS1

4. An EDSS score of 0 to 5.5

5. Significant inflammatory disease activity in the last year despite treatment withstandard disease modifying therapy (interferon beta, glatiramer acetate, dimethylfumarate, teriflunomide, fingolimod, natalizumab) a. Significant inflammatory disease activity is defined by: i. One or moreclinically reported multiple sclerosis (MS) relapse(s), ii. AND 1 or more T1Gd-enhanced lesion(s), iii. OR three or more new or enlarging T2 lesions on magneticresonance imaging (MRI) The relapse(s) must have been treated with iv or oral highdose corticosteroids prescribed by a neurologist, and must have occurred 3 or moremonths after the onset of an immunomodulatory treatment, as MS immunomodulatorytreatment may reach full effect after 3 months or more2.

6. The patient is a RRMS-patient referred from neurological departments in Norway,Denmark, Sweden or possibly other European countries to an assigned study site.

7. Signed informed consent and expected patient cooperation regarding the treatmentschemes and procedures planned in the treatment and follow-up periods must beobtained and documented according to ICH GCP and national/local regulations.

Exclusion Criteria:

1. Known hypersensitivity or other known serious side effects for any of the studymedications, including co-medications such as high-dose glucocorticosteroids

2. Any illness or prior treatment that in the opinion of the investigators wouldjeopardize the ability of the patient to tolerate aggressive chemotherapy orhigh-dose glucocorticosteroids

3. Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus,toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigenpositivity and/or hepatitis C PCR positivity verified at Visit 1

4. Patients without a history of chickenpox or without vaccination against varicellazoster virus (VZV), unless tested for antibodies to VZV. VZV negative patients canonly be included if they receive vaccination against VZV at least 6 weeks prior toinclusion.

5. Current or previous treatments with long-term effects that may influence thetreatment effects or potential toxicities/side effects of the treatment arms. Thisincludes, but is not restricted to previous treatment with rituximab, mitoxantrone,alemtuzumab, cladribin and ocrelizumab

6. Immunocompromised patients, or patients currently reveiving immunosuppressive ormyelosuppressive therapy

7. Treatment with glucocorticoids or ACTH within one month prior to start of studytreatment

8. Having experienced an MS relapse within one month prior to study inclusion

9. Prior or current major depression

10. Prior or current psychiatric illness, mental deficiency or cognitive dysfunctioninfluencing the patient ability to make an informed consent or comply with thetreatment and follow-up phases of this protocol.

11. Prior or current alcohol or drug dependencies

12. Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhytmia, unstable oradvanced ischemic heart disease (NYHA III or IV)

13. Significant hypertension: BP > 180/110

14. Active malignancy, or prior history of malignancy except localized basal cell,squamous skin cancer or carcinoma in situ of the cervix.

15. Known untreated or unregulated thyroid disease

16. Failure to willingly accept or comprehend risk of irreversible sterility as a sideeffect of therapy

17. WBC < 1,5 x 109/L if not caused by a reversible effect of documented ongoingmedication. If WBC < 1,5 x 109/L is caused by a reversible effect of documentedongoing medication the WBC count must be > 1,5 x 109/L before start of studytreatment.

18. Platelet (thrombocyte) count < 100 x 109/L

19. ALAT and/or ASAT more than 2 times the upper normal reference limit (UNL)

20. Serum creatinine > 200 µmol/L

21. Serum bilirubin > ULN

22. Moderate or severely impaired kidney function (creatinine-clearance below 60 ml/min)

23. Presence of metallic objects implanted in the body that would preclude the abilityof the patient to safely have MRI exams

24. Diagnosis of primary progressive MS

25. Diagnosis of secondary progressive MS

26. Treatment with natalizumab and fingolimod within the last 2 months, and treatmentwith dimetylfumurat within the last month (washout must be performed as specified insection 5.1) prior to start of study medication.

27. Use of teriflunomide (Aubagio®) within the previous 2 years unless cleared from thebody (plasma concentration < 0.02 mcg/ml following elimination from the body withcholestyramine or activated powdered charcoal) as specified in section 5.1 prior tostart of study medication.

28. Any hereditary neurological disease such as Charcot-Marie-Tooth disease orSpinocerebellar ataxia

29. Any disease that can influence the patient safety and compliance, or the evaluationof disability

30. History of hypersensitivity reaction to rabbit

31. Women who are pregnant, breast-feeding, or who plan to become pregnant within thetimeframe of this study

32. Currently enrolled in another investigational device or drug study, or less than 30days since ending another investigational device or drug study(s), or receivingother investigational treatment(s). Patients participating in a purely observationaltrial will not be excluded.