RAM-MS

Phase 1

Active, not recruiting

• Conditions: Multiple sclerosis; MedDRA version: 21.1Level: PTClassification code: 10063399Term: Relapsing-remitting multiple sclerosis Class: 100000004852; Therapeutic area: Diseases [C] - Immune System Diseases [C20]; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: CTIS2024-510630-40-00
• Lead Sponsor: Helse Bergen HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-30
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Age between =18 to =50, both genders, Women of childbearing potential* (WOCBP) and men in a sexual relation with WOCBP must 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 used consistently and correctly for the duration of the study OR until 4, 6 and 12 months after last dose administered for alemtuzumab, cladribine or ocrelizumab respectively (the longest alternative applies). If treated with cladribine, women must use double barrier method during each treatment course and until 4 weeks after last dose in each treatment course is administered., Diagnosis of RRMS using revised McDonald criteria of clinically definite MS, An EDSS score of 0 to 5.5, Significant inflammatory disease activity in the last year despite treatment with standard disease modifying therapy (interferon beta, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, natalizumab) a.Significant inflammatory disease activity is defined by: i.One or more clinically reported multiple sclerosis (MS) relapse(s), ii.AND 1 or more T1 Gd-enhanced lesion(s), iii.OR three or more new or enlarging T2 lesions on magnetic resonance imaging (MRI) The relapse(s) must have occurred 3 or more months after the onset of an immunomodulatory treatment, as MS immunomodulatory treatment may reach full effect after 3 months or more., The patient is a RRMS-patient referred from neurological departments in Norway, Denmark, Sweden, the Netherlands (or potentially from other countries participating in the study), to an assigned study site., Signed informed consent and expected patient cooperation regarding the treatment schemes and procedures planned in the treatment and follow-up periods must be obtained and documented according to ICH GCP and national/local regulations.

Exclusion Criteria

Known hypersensitivity or other known serious side effects for any of the study medications, including co-medications such as high-dose glucocorticosteroids, Prior or current alcohol or drug dependencies, Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhytmia, unstable or advanced ischemic heart disease (NYHA III or IV), Significant hypertension: BP > 180/110, Active malignancy or prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix., Known untreated or unregulated thyroid disease, Failure to willingly accept or comprehend risk of irreversible sterility as a side effect of therapy, WBC < 1,5 x 109/L if not caused by a reversible effect of documented ongoing medication. If WBC < 1,5 x 109/L is caused by a reversible effect of documented ongoing medication the WBC count must be > 1,5 x 109/L before start of study treatment., Platelet (thrombocyte) count < 100 x 109/L, ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN), Serum creatinine > 200 µmol/L, Any illness or prior treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy or high-dose glucocorticosteroids, Serum bilirubin > ULN, Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams, Diagnosis of primary progressive MS, Diagnosis of secondary progressive MS, Treatment with natalizumab and fingolimod within the last 2 months, and treatment with dimetylfumurat within the last month (washout must be performed as specified in section 5.1) prior to start of study medication., Use of teriflunomide (Aubagio®) within the previous 2 years unless cleared from the body (plasma concentration < 0.02 mcg/ml following elimination from the body with cholestyramine or activated powdered charcoal) as specified in section 5.1 prior to start of study medication., Any hereditary neurological disease such as Charcot-Marie-Tooth disease or Spinocerebellar ataxia, Any disease that can influence the patient safety and compliance, or the evaluation of disability, History of hypersensitivity reaction to rabbit, Women who are pregnant, breast-feeding, or who plan to become pregnant within the timeframe of this study, Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity verified at Visit 1, Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded., Immunocompromised patients, or patients currently reveiving immunosuppressive or myelosuppressive therapy, Moderate or severely impaired kidney function (creatinine-clearance below 60 ml/min), Patients without a history of chickenpox or without vaccination against varicella zoster virus (VZV), unless tested for antibodies to VZV. VZV negative patients can only be included if they receive vaccination against VZV at least 6 weeks prior to inclusion., Current or previous treatments with long-term effects that may influence the treatment effects or potential toxicities/side effects of the treatment arms. This includes, but is not restricted to previous treatment with mitoxant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this prospective, randomized study is to investigate the efficacy and safety of HSCT compared to the comparator group (alemtuzumab, cladribine or ocrelizumab) in patients with aggressive relapsing remitting MS.;Secondary Objective: In Norway, the clinical study is supplemented with a health economic evaluation.;Primary end point(s): The primary efficacy endpoint of this prospective, randomized study is to determine differences between patients in the 2 treatment arms according to the following criteria: Proportion of patients with no evidence of disease activity after a 2 year (96 week) and 5 year (240 week) period. NEDA is the absence of a protocol defined disease activity event.