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Clinical Trials/2024-510630-40-00
2024-510630-40-00
Active, not recruiting
Phase 3

Randomized Autologous heMatopoietic stem cell transplantation versus alemtuzumab, cladribine or ocrelizumab for patients with relapsing remitting Multiple Sclerosis (RAM-MS)

Helse Bergen HF7 sites in 4 countries100 target enrollmentStarted: June 6, 2024Last updated:
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Overview

Phase
Phase 3
Status
Active, not recruiting
Enrollment
100
Locations
7
Primary Endpoint
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.
OverviewEligibility CriteriaOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Overview

Brief Summary

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.

Eligibility Criteria

Ages
18 years to 64 years (18-64 Years)
Accepts Healthy Volunteers
No

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)

Outcomes

Primary Outcomes

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.

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.

Secondary Outcomes

  • Proportion of patients with no evidence of disease activity, including atrophy (NEDA 4), as per protocol defined disease activity events (as defined in section 2.2) plus atrophy (measured yearly atrophy above threshold of 0, 4 %) during a 2 year (96 week) and a 5 year (240 week) period4, with re-baseline for brain athrophy at 48 weeks.
  • Time to first protocol-defined disease activity event as defined in section 2.2
  • Change in EQ-5D-5L from baseline to Week 96, and from baseline to Week 240
  • Change in Fatigue Severity Scale (FSS) from baseline to Week 96, and from baseline to Week 240
  • Change in Multiple Sclerosis Impact Scale (MSIS)-29 from baseline to Week 96, and from baseline to Week 240
  • Change in EDSS from baseline (Visit 4.1) to Week 96 , and from baseline to Week 240
  • The proportion of patients who, at Week 96 and at Week 240, have protocol-defined Confirmed Disability Improvement (CDI) , confirmed stable EDSS or Confirmed Disability Progression (CDP) compared to baseline
  • Annualized rate of protocol-defined relapses during 96 weeks and 240 weeks from start of study treatment
  • Time to onset of first protocol-defined relapse from start of study treatment
  • Change in MRI T2-weighted hyperintense lesion volume from baseline to Weeks 48 and 96, and from baseline to Week 144, 192 and 240
  • Change in MRI T1-weighted hypointense lesion volume from baseline to Weeks 48 and 96, and from baseline to Week 144, 192 and 240
  • Change in brain volume from re-baseline at week 48, to week 96, from re-baseline at week 48, to Week 144, 192 and 240
  • Time to detection of a new MRI T2 lesion
  • Total number of MRI T1-weighted Gd-enhanced lesions at weeks 24, 48, 96, 144, 192 and 240
  • Proportion of patients free from T1 Gd-enhancing lesions at weeks 24, 48, 96, 144, 192 and 240
  • Change in Nine-hole-peg test (9-HPT) score from baseline to week 48, 96 and 240
  • Change in Timed 25 foot walk (T25FW) score from baseline to week 48, 96 and 240
  • Change in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score from baseline to week 96 and 240
  • Overall survival rate at week 96 and 240
  • Work productivity and activity impairment at week 96, 144, 192 and 240

Investigators

Sponsor Class
Hospital/Clinic/Other health care facility
Responsible Party
Principal Investigator
Principal Investigator

Lars Bø

Scientific

Helse Bergen HF

Study Sites (7)

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