Multiple SclerosisPhase 3RAM-MSNCT03477500
Randomized Autologous heMatopoietic Stem Cell Transplantation Versus Alemtuzumab, Cladribine or Ocrelizumab for RRMS (RAM-MS)
A Phase 3 study testing Cyclophosphamide and ATG, Alemtuzumab and Cladribine Pill in people with Multiple Sclerosis, run by Haukeland University Hospital at 8 sites in 4 countries.
Trial summary
This study is a randomized multicentre, multinational, treatment interventional study of RRMS patients with breakthrough inflammatory disease activity in spite of ongoing standard immunomodulatory medication. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Cyclophosphamide and ATG, Alemtuzumab and Cladribine Pill
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 21 Mar 2018to 21 Mar 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- Diagnosis of RRMS using revised McDonald criteria of clinically definite MS1
- 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)
- 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 been treated with iv or oral high dose corticosteroids prescribed by a neurologist, and 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 more2.
- The patient is a RRMS-patient referred from neurological departments in Norway, Denmark, Sweden or possibly other European countries 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.
Who cannot join
- Known hypersensitivity or other known serious side effects for any of the study medications, including co-medications such as high-dose glucocorticosteroids
- 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
- 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
- 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 rituximab, mitoxantrone, alemtuzumab, cladribin and ocrelizumab
- Immunocompromised patients, or patients currently reveiving immunosuppressive or myelosuppressive therapy
Show all 32Show fewer
- Treatment with glucocorticoids or ACTH within one month prior to start of study treatment
- Having experienced an MS relapse within one month prior to study inclusion
- Prior or current major depression
- Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
- 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 (UNL)
- Serum creatinine > 200 µmol/L
- Serum bilirubin > ULN
- Moderate or severely impaired kidney function (creatinine-clearance below 60 ml/min)
- 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
- 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.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Norway4 sites
Haukeland University Hospital
Bergen
Akershus University Hospital
Oslo
University Hospital of North Norway
Tromsø
St. Olav's University Hospital
Trondheim
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg
Akademiska sjukhuset
Uppsala
About this study
Official title: Randomized Autologous heMatopoietic Stem Cell Transplantation Versus Alemtuzumab, Cladribine or Ocrelizumab for Patients With Relapsing Remitting Multiple Sclerosis (RAM-MS)
This study is a randomized multicentre, multinational, treatment interventional study of RRMS patients with breakthrough inflammatory disease activity in spite of ongoing standard immunomodulatory medication. The study has two treatment arms; arm A: HSCT (hematopoietic stem cell transplantation) and arm B: alemtuzumab, cladribine or ocrelizumab. A pre-planned 3-year follow-up extension period will be performed depending on future funding.
The aim of the study is to assess the effectiveness and side effects of a new treatment intervention in RRMS; HSCT, and, thereby, the value of HSCT in clinical practice. Data from recently published patient series indicate that HSCT may have a significantly higher treatment effect than currently registered RRMS immunomodulatory treatments. This study will determine the relative role of HSCT versus alemtuzumab, cladribine or ocrelizumab.
Read the detailed description
This is a randomized study of autologous HSCT using a low intensity, non-ablative conditioning regimen with cyclophosphamide and ATG versus treatment with the currently presumed best available immunomodulatory medication (alemtuzumab, cladribine or ocrelizumab) in RRMS patients with significant inflammatory disease activity in spite of ongoing immunomodulatory MS treatment.
Significant disease activity is defined as having one or more clinically reported multiple sclerosis (MS) relapse(s), AND 1 or more T1 Gd-enhanced lesion(s), OR three or more new or enlarging T2 lesions on magnetic resonance imaging (MRI) over the last year while being treated on immunomodulatory medication by standard national guidelines. The relapse(s) must have occurred 3 or more months after the onset of an immunomodulatory treatment, as immunomodulatory treatment in MS may reach full effect after 3 months or more.
Both the knowledge of the treatment effect of registered immunomodulatory therapies for RRMS, and the number of treatments approved for RRMS by the European Medicines Agency (EMA) are rapidly increasing. During the study period, there may thus appear new supplementing information on other MS immunomodulatory treatments that favour the use of a new comparator (replacing or supplementing the comparators). This will be evaluated by the PMC if applicable during the study period and the planned extension period.
If the treatment efficacy obtained by HSCT is better than the currently most efficacious standard, immunomodulatory treatment in randomized treatment trials, HSCT will likely be approved as a part of the standard treatment recommendations for a significant proportion of RRMS patients. A randomized study regarding with statistical power to evaluate the clinical outcome of autologous HSCT compared to a standard immunomodulatory treatment in MS has not yet been published. Except for Sweden, HSCT is currently not registered as a part of standard MS treatment in the public health services of Europe. The HSCT regimen for the study will be identical to the regimen used in similar patient populations in Sweden, Norway and Denmark.
Alemtuzumab, cladribine or ocrelizumab have been chosen as the primary comparators, because they are the immunomodulatory medication currently authorised by the EMA for treatment of RRMS with the most favourable therapeutic effects. In a meta-analysis of immunomodulatory treatment effects in RRMS, thse medications had the most eminent reduction of annualized relapse rate and 3 month confirmed disability progression.
In this study, a health economic evaluation will be included. Accordingly, the proposed study should provide a robust basis for future official decisions regarding the role of HSCT in RRMS treatment.
- Conditions
- Multiple Sclerosis
- Being tested
- Cyclophosphamide and ATG, Alemtuzumab, Cladribine Pill, Ocrelizumab
- Keywords
- multiple sclerosis,, HSCT, alemtuzumab, RCT
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide and ATGDrug
Also called Sendoxan
Hematopoetic stem cell transplantation
AlemtuzumabDrug
Also called Lemtrada
Alemtuzumab (Lemtrada)
Cladribine PillDrug
Also called Mavenclad
Cladribine (Mavenclad)
OcrelizumabDrug
Also called Ocrevus
Ocrelizumab (Ocrevus)
| Study group | Role | What they receive |
|---|---|---|
| HSCT (Cyclophosphamide and ATG) | Experimental | Day 1: Cyclophosphamide 2.0 g/m2 body surface area Days 5-10: Granulocyte colony stimulating factor (filgrastim) 5 mcg/kg body weight/day sc.
Day 11 and until apheresis is discontinued: Granulocyte colony stimulating factor (filgrastim) 5 mcg/kg body weight x 2 sc/day.
HSCT days -5 to -2: Cyclophosphamide 50 mg/kg/day. HSCT days -5 to -1: Anti-thymocyte globulin (ATG-rabbit, Thymoglobuline®) 0.5 mg/kg body weight iv on day -5, 1.0 mg ATG-rabbit/kg will be given iv on day -4, and 1.5 mg ATG-rabbit /kg will be given iv on days -3,-2 and -1 over 10 hours.
HSCT day 0: Reinfusion of a minimum of 3,0 x 106 CD 34+ cells/kg body weight. Receives: Drug: Cyclophosphamide and ATG |
| Alemtuzumab, Cladribine or Ocrelizumab | Active comparator | Alemtuzumab, Cladribine or Ocrelizumab administered after the label of the study drug. Receives: Drug: Alemtuzumab; Drug: Cladribine Pill; Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with no evidence of disease activity (NEDA, as defined per protocol).
A protocol-defined disease activity event is the occurrence of at least one of the following:
- A new T1 Gd-enhanced lesion on MRI of the brain and spinal cord
- A new T2 hyperintense lesion on MRI of brain and spinal cord
- A protocol-defined MS relapse (see below)
- 24 week confirmed disability progression based on increases in Expanded Disability Status Scale (EDSS)
Measured: 2 year (96 week) period with a 5 year (240 week) planned extension
Secondary outcomes (16)
NEDA-4
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 %)
Measured: 2 year (96 week) period
Pre-planned study extension:
Proportion of patients who have NEDA 4
Measured: 5 year (240 week) period.
Time to first protocol-defined disease activity event
Time to first sign of new disease activity, as measured as new relapses, EDSS-progression, MRI-activity or brain atrophy
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Expanded Disability Status scale (EDSS) from baseline (Visit 4.1) to Weeks 96 and 240
EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
The proportion of patients who, at Week 96, have protocol-defined Confirmed Disability Improvement (CDI) , confirmed stable EDSS or Confirmed Disability Progression (CDP) compared to baseline
Disability progression, as measured with EDSS. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Annualized rate of protocol-defined relapses during 96 weeks
ARR
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Time to onset of first protocol-defined relapse
Time to first relapse
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in MRI T2-weighted hyperintense lesion volume from baseline to weeks 96 (and 240)
Change in T2-weighted hyperintense lesion volume
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in MRI T1-weighted hypointense lesion volume from baseline to weeks 96 (and 240)
Change in MRI T1-weighted hypointense lesion volume
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in brain volume from baseline to week 96 (and week 240)
Change in brain volume
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Time to detection of a new MRI T2 lesion
Time to New MRI T2-lesion
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Total number of MRI T1-weighted Gd-enhanced lesions
Number of Gd-lesions
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Proportion of patients free from T1 Gd-enhancing lesions
Proportion of patients free from T1 Gd-enhancing lesions
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Nine-hole-peg test (9-HPT) score from baseline to week 96 (and 240)
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Timed 25 Foot Walk (T25FW) score from baseline to week 48, 96 (and 240)
The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. The score for the T25FW is the average of the 2 completed trials. The 95% CI of the percentage is based on normal approximation.
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score from baseline to week 96 (and 240)
BICAMS is a composite cognitive assessment tool comprising of the three components : Symbol Digit Modalities Test (SDMT) , California Verbal Learning Test-II (CVLT-II) and Brief visuospatial memory test- Revised (BVMT-R)
Measured: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2018
- Study start21 Mar 2018
- Primary completion21 Nov 2026 (estimated)
- Study completion21 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lars Bø, MD, Phd, Study director, Haukeland University HospitalAnne Kristine Lehmann, MD, PhD, Study chair, Haukeland University HospitalAstrid Kittang, MD, PhD, Study chair, Haukeland University HospitalEinar Kristoffersen, MD, PhD, Study chair, Haukeland University HospitalØivind Torkildsen, MD, PhD, Study chair, Haukeland University HospitalTrygve Holmøy, MD, PhD, Principal investigator, University Hospital, AkershusMargitta Kampman, MD, PhD, Principal investigator, Tromsø University HospitalKathrine K Liane, MD, Principal investigator, St. Olavs Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03477500
- Sponsor's protocol ID
- 2017-001362-25
- Other IDs
- 2017
- Acronym
- RAM-MS
- Status last verified
- Jun 2025
- First submitted
- 13 Feb 2018
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for all primary and secondary outcome measures will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Autologous heMatopoietic Stem Cell Transplantation Versus Alemtuzumab, Cladribine or Ocrelizumab for Patients With Relapsing Remitting Multiple Sclerosis (RAM-MS)
- ClinicalTrials.gov ID
- NCT03477500
- Acronym / sponsor ID
- RAM-MS / 2017-001362-25
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis,, HSCT, alemtuzumab, RCT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 21 Mar 2018 (actual)
- Primary completion
- 21 Nov 2026 (estimated)
- Study completion
- 21 Mar 2028 (estimated)
- First posted
- 26 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a randomized multicentre, multinational, treatment interventional study of RRMS patients with breakthrough inflammatory disease activity in spite of ongoing standard immunomodulatory medication. The study has two treatment arms; arm A: HSCT (hematopoietic stem cell transplantation) and arm B: alemtuzumab, cladribine or ocrelizumab. A pre-planned 3-year follow-up extension period will be performed depending on future funding.
The aim of the study is to assess the effectiveness and side effects of a new treatment intervention in RRMS; HSCT, and, thereby, the value of HSCT in clinical practice. Data from recently published patient series indicate that HSCT may have a significantly higher treatment effect than currently registered RRMS immunomodulatory treatments. This study will determine the relative role of HSCT versus alemtuzumab, cladribine or ocrelizumab.
Detailed description
This is a randomized study of autologous HSCT using a low intensity, non-ablative conditioning regimen with cyclophosphamide and ATG versus treatment with the currently presumed best available immunomodulatory medication (alemtuzumab, cladribine or ocrelizumab) in RRMS patients with significant inflammatory disease activity in spite of ongoing immunomodulatory MS treatment.
Significant disease activity is defined as having one or more clinically reported multiple sclerosis (MS) relapse(s), AND 1 or more T1 Gd-enhanced lesion(s), OR three or more new or enlarging T2 lesions on magnetic resonance imaging (MRI) over the last year while being treated on immunomodulatory medication by standard national guidelines. The relapse(s) must have occurred 3 or more months after the onset of an immunomodulatory treatment, as immunomodulatory treatment in MS may reach full effect after 3 months or more.
Both the knowledge of the treatment effect of registered immunomodulatory therapies for RRMS, and the number of treatments approved for RRMS by the European Medicines Agency (EMA) are rapidly increasing. During the study period, there may thus appear new supplementing information on other MS immunomodulatory treatments that favour the use of a new comparator (replacing or supplementing the comparators). This will be evaluated by the PMC if applicable during the study period and the planned extension period.
If the treatment efficacy obtained by HSCT is better than the currently most efficacious standard, immunomodulatory treatment in randomized treatment trials, HSCT will likely be approved as a part of the standard treatment recommendations for a significant proportion of RRMS patients. A randomized study regarding with statistical power to evaluate the clinical outcome of autologous HSCT compared to a standard immunomodulatory treatment in MS has not yet been published. Except for Sweden, HSCT is currently not registered as a part of standard MS treatment in the public health services of Europe. The HSCT regimen for the study will be identical to the regimen used in similar patient populations in Sweden, Norway and Denmark.
Alemtuzumab, cladribine or ocrelizumab have been chosen as the primary comparators, because they are the immunomodulatory medication currently authorised by the EMA for treatment of RRMS with the most favourable therapeutic effects. In a meta-analysis of immunomodulatory treatment effects in RRMS, thse medications had the most eminent reduction of annualized relapse rate and 3 month confirmed disability progression.
In this study, a health economic evaluation will be included. Accordingly, the proposed study should provide a robust basis for future official decisions regarding the role of HSCT in RRMS treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HSCT (Cyclophosphamide and ATG) | Experimental | Drug: Cyclophosphamide and ATGDay 1: Cyclophosphamide 2.0 g/m2 body surface area Days 5-10: Granulocyte colony stimulating factor (filgrastim) 5 mcg/kg body weight/day sc. Day 11 and until apheresis is discontinued: Granulocyte colony stimulating factor (filgrastim) 5 mcg/kg body weight x 2 sc/day. HSCT days -5 to -2: Cyclophosphamide 50 mg/kg/day. HSCT days -5 to -1: Anti-thymocyte globulin (ATG-rabbit, Thymoglobuline®) 0.5 mg/kg body weight iv on day -5, 1.0 mg ATG-rabbit/kg will be given iv on day -4, and 1.5 mg ATG-rabbit /kg will be given iv on days -3,-2 and -1 over 10 hours. HSCT day 0: Reinfusion of a minimum of 3,0 x 106 CD 34+ cells/kg body weight. |
| Alemtuzumab, Cladribine or Ocrelizumab | Active comparator | Drug: Alemtuzumab, Drug: Cladribine Pill, Drug: OcrelizumabAlemtuzumab, Cladribine or Ocrelizumab administered after the label of the study drug. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
- Diagnosis of RRMS using revised McDonald criteria of clinically definite MS1
- 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)
Key exclusion criteria (32 listed)
- Known hypersensitivity or other known serious side effects for any of the study medications, including co-medications such as high-dose glucocorticosteroids
- 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
- 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
- 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 rituximab, mitoxantrone, alemtuzumab, cladribin and ocrelizumab
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide and ATGAlso: SendoxanHematopoetic stem cell transplantation | Drug | HSCT (Cyclophosphamide and ATG) |
| AlemtuzumabAlso: LemtradaAlemtuzumab (Lemtrada) | Drug | Alemtuzumab, Cladribine or Ocrelizumab |
| Cladribine PillAlso: MavencladCladribine (Mavenclad) | Drug | Alemtuzumab, Cladribine or Ocrelizumab |
| OcrelizumabAlso: OcrevusOcrelizumab (Ocrevus) | Drug | Alemtuzumab, Cladribine or Ocrelizumab |
Primary outcome
Proportion of patients with no evidence of disease activity (NEDA, as defined per protocol).
Time frame: 2 year (96 week) period with a 5 year (240 week) planned extension
A protocol-defined disease activity event is the occurrence of at least one of the following: * A new T1 Gd-enhanced lesion on MRI of the brain and spinal cord * A new T2 hyperintense lesion on MRI of brain and spinal cord * A protocol-defined MS relapse (see below) * 24 week confirmed disability progression based on increases in Expanded Disability Status Scale (EDSS)
16 secondary outcomes
NEDA-4
Time frame: 2 year (96 week) period
Pre-planned study extension:
Time frame: 5 year (240 week) period.
Time to first protocol-defined disease activity event
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Expanded Disability Status scale (EDSS) from baseline (Visit 4.1) to Weeks 96 and 240
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
The proportion of patients who, at Week 96, have protocol-defined Confirmed Disability Improvement (CDI) , confirmed stable EDSS or Confirmed Disability Progression (CDP) compared to baseline
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Annualized rate of protocol-defined relapses during 96 weeks
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Time to onset of first protocol-defined relapse
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in MRI T2-weighted hyperintense lesion volume from baseline to weeks 96 (and 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in MRI T1-weighted hypointense lesion volume from baseline to weeks 96 (and 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in brain volume from baseline to week 96 (and week 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Time to detection of a new MRI T2 lesion
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Total number of MRI T1-weighted Gd-enhanced lesions
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Proportion of patients free from T1 Gd-enhancing lesions
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Nine-hole-peg test (9-HPT) score from baseline to week 96 (and 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in Timed 25 Foot Walk (T25FW) score from baseline to week 48, 96 (and 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Change in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score from baseline to week 96 (and 240)
Time frame: 2 year (96 week) period, with planned extension for 5 year (240 week) period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Study site (in Norwegian)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for all primary and secondary outcome measures will be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Bø, MD, Phd study director
Haukeland University Hospital
Anne Kristine Lehmann, MD, PhD study chair
Haukeland University Hospital
Astrid Kittang, MD, PhD study chair
Haukeland University Hospital
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide and ATG, Alemtuzumab and Cladribine Pill in people with Multiple Sclerosis, run by Haukeland University Hospital at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Norway, Sweden, Denmark, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with no evidence of disease activity (NEDA, as defined per protocol). (time frame: 2 year (96 week) period with a 5 year (240 week) planned extension). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.