Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
90
Countries
1
Sites
8
Relapsing Remitting Multiple Sclerosis
The primary outcome is the occurrence of any evidence of multiple sclerosis disease activity (NEDA-3) over 36 months, analyzed as time-to-event
Key facts
- Sponsor
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 31 Oct 2024 → ongoing
- Decision date (initial)
- 2024-12-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-515470-26-00
- EudraCT number
- 2022-002654-95
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Therapy
The primary outcome is the occurrence of any evidence of multiple sclerosis disease activity (NEDA-3) over 36 months, analyzed as time-to-event
Secondary objectives 1
- Secondary outcomes at 36 months: ¿Incidence of serious adverse events and all-cause mortality ¿Annual relapse rate ¿Number of newT2/gadolinium enhancing T1lesions ¿Incidence of confirmed disability improvement and confirmed disability progression ¿Changes in brain volume ¿Changes in serum neurofilament light chain concentration ¿Changes in BICAMS scores ¿Changes in MSFC scores ¿Changes in the IgG/IgM index in the cerebrospinal fluid ¿Changes in the peripheral retinal nerve fiber layer and inner nuclear layer thickness ¿Changes in patient’s reported outcomes ¿Percentage of patients of child-bearing potential who maintains or resumes menstruation ¿Variation in anti-Mullerian hormone levels and antral follicular count ¿Variation in sperm count motility and morphology ¿Changes in advanced MRI metrics of tissue integrity inflammation and functional plasticity ¿Immunological changes associated with immune tolerance ¿Changes in the gut microbiota
Conditions and MedDRA coding
Relapsing Remitting Multiple Sclerosis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10063399 | Relapsing-remitting multiple sclerosis | 100000004852 |
Study design 9 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | screening Participants will undergo screening visit (Visit 1) with extensive clinical evaluation in order to assess the inclusion and exclusion criteria to study entry. All screening assessments should be completed within 3 weeks from randomization.
|
Randomised Controlled | Single | [{"id":151056,"code":4,"name":"Analyst"},{"id":151057,"code":2,"name":"Investigator"}] | comparator arm: best available therapy (BAT) Test Arm: AHSCT |
| 2 | Randomization At Visit 2, once eligibility criteria are confirmed, Participants will be randomized at a 1:1 ratio, after stratification according to the V2 EDSS score (one group with 2 ≤ EDSS ≤ 4 and another one with 4.5 ≤ EDSS ≤ 6).
|
Randomised Controlled | Single | [{"id":151059,"code":2,"name":"Investigator"},{"id":151060,"code":4,"name":"Analyst"}] | Test Arm: AHSCT comparator arm: Best Available Therapy (BAT) |
| 3 | Pre treatment assessments and baseline evaluations Within 4-6 weeks after Visit 2 pre-treatment assessments will be performed according to allocated treatment group. Procedures aimed at fertility preservation will be offered to AHSCT allocated patients. At V3 baseline assessments such as MRI and neurological evaluations will be performed
|
Randomised Controlled | Single | [{"id":151062,"code":2,"name":"Investigator"},{"id":151063,"code":4,"name":"Analyst"}] | comparator arm: Best Available Therapy Test Arm: AHSCT |
| 4 | BAT Treatment start During V4 (up to 4 weeks after randomization) the study subjects allocated to BAT will receive the first dose of the BAT treatment chosen by the treating neurologists according to their clinical judgement. BAT will be administered and monitored as per license.
|
Randomised Controlled | Single | [{"id":151066,"code":2,"name":"Investigator"},{"id":151065,"code":4,"name":"Analyst"}] | comparator arm: Best available therapy |
| 5 | BAT treatment and clinical follow-up After the first BAT dose, BAT administration will continue and will be monitored as per license. Follow-up visits will be scheduled every 3 months from Month 3 to Month 36 post randomization, then every 6 months up to Month 60. Safety lab tests will be performed every 3 months throughout the whole study.
|
Randomised Controlled | Single | [{"id":151068,"code":4,"name":"Analyst"},{"id":151069,"code":2,"name":"Investigator"}] | comparator arm: BAT |
| 6 | AHSCT mobilization and harversting (visit 4.1) Patients allocated to the AHSCT arm will be hospitalized in the Transplant Units for mobilization and harvesting of the periferal blood stem cells (PBSC).
PBCS are mobilized by the use of cyclophosphamide 4g/sqm in a single dose. After 5 days, granulocyte colony stimulating factor (filgrastim) 10 mcg/Kg/day will be administered until the completion of stem cells collection. In case of inadequate mobilization of CD34+ plerixafor could be used in addition to filgrastim. Apheresis begins according to local routines and continues until a minimum of 3 x 106 CD 34+ cells/kg body weight is obtained. The stem cell graft is processed and stored in accordance with local routines and national regulations.
|
Randomised Controlled | Single | [{"id":151071,"code":4,"name":"Analyst"},{"id":151072,"code":2,"name":"Investigator"}] | Test Arm: AHSCT |
| 7 | AHSCT Conditioning and stem cell infusion (visit 4.2) Conditioning regimen includes BCNU (carmustine, 300 mg/sqm at day -6), cytosine-arabinoside (200 mg/sqm), etoposide (200 mg/sqm from day -5 to day -2) and melphalan (140 mg/sqm at day -1). Treatment day (day 0) of the AHSCT procedure corresponds to stem cell graft infusion. The frozen graft containing 3-8 x 106 CD 34+ cells/kg body weight is thawed and infused iv (day 0). Rabbit Anti-T globulin (ATG) is administered at day +1 and +2 at a total dosage of 5 mg/Kg. ATG infusions are preceded by methylprednisolone 250 mg iv, paracetamol po or iv and Chlorpheniramine po or iv. Additional prednisolone is given on days 0, +1 and +2 (25mg).
|
Randomised Controlled | Single | [{"id":151075,"code":2,"name":"Investigator"},{"id":151074,"code":4,"name":"Analyst"}] | Test Arm: AHSCT |
| 8 | AHSCT weekly follow up After discharge from hospital, weekly follow-up at the Transplant Unit is required until Day +60 after AHSCT for safety monitoring (blood test and consultation) and clinical care.
|
Randomised Controlled | Single | [{"id":151077,"code":4,"name":"Analyst"},{"id":151078,"code":2,"name":"Investigator"}] | Test Arm: AHSCT |
| 9 | AHSCT clinical follow-up For patients treated with AHSCT, clinical follow-up visits at the neurology Units will be scheduled every 3 months post randomization until Month 36; thereafter, visits will be performed every 6 months until Month 60. Safety lab tests will be performed every 3 months throughout the whole study.
|
Randomised Controlled | Single | [{"id":151081,"code":2,"name":"Investigator"},{"id":151080,"code":4,"name":"Analyst"}] | Test Arm: AHSCT |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Diagnosis of relapsing remitting MS according to the 2017 Mc Donald’s criteria.
- Treatment-resistant MS, defined as the occurrence of disease activity following ≥ 6 months of treatment with an oral agent or a monoclonal antibody in the 12 months prior to the screening visit (≥ 1 relapse AND the occurrence of MRI evidence of disease activity, defined as ≥ 1 gadolinium-enhancing lesion or ≥ 1 new non-enhancing T2 lesion compared to a reference scan obtained not more than 18 months prior to the screening visit). OR aggressive-highly active MS, characterized by the presence of at least one disabling relapse in the 6 months prior to the screening visit AND the evidence at MRI of ≥ 1 gadolinium enhancing lesion or ≥ 1 new non-enhancing T2 lesion compared to a reference scan obtained not more than 6 months prior to the screening visit. For aggressive-highly active MS, the following additional inclusion criteria must be present: high brain lesion load or the presence of spinal cord lesions.
- Age ≥ 18 and ≤ 55.
- Expanded Disability Status Scale (EDSS) ≥ 2.0 and ≤ 6.0.
- Candidacy for treatment with at least one of the following diseases modifying treatments (DMT): natalizumab, alemtuzumab, ocrelizumab and/or ublituximab. Candidacy must include no prior treatment failure with the candidate DMT and no contraindication to the candidate DMT.
Exclusion criteria 31
- Diagnosis of primary and secondary progressive MS according to the 2017 McDonald criteria
- Treatment with natalizumab, fingolimod and dimethyl-fumarate within the last 4 weeks to allow for proper wash-out. For previously natalizumab-treated patients with a positive John Cunningham virus antibody index, a negative CSF JCV-PCR is required.
- Treatment with teriflunomide within the last 2 years unless cleared from the body (plasma concentration < 0.02 mcg/ml following elimination from the body with cholestyramine or activated powdered charcoal).
- Treatment with ocrelizumab, ofatumumab, ublituximab, alemtuzumab and cladribine within the last 3 months.
- Known hypersensitivity or other known serious side effects for any of the study medications, including co-medications such as high-dose steroids and rabbit anti-thymocyte globulin.
- Brain MRI or Cerebrospinal fluid (CSF) examination indicating or suggesting a diagnosis of progressive multifocal leukoencephalopathy (PML).
- If white blood cells < 1,5 x 109/L and/or lymphocytes CD4+ < 200/mm3 because of a reversible effect of documented ongoing medication, the WBC count must be ≥ 1,5 x 109/L and lymphocytes CD4+ ≥ 200/mm3 before start of study treatment.
- In case of unexplained cytopenia, polycythemia, thrombocythemia diagnosis of myelodysplastic syndrome must be ruled out before including patient in the protocol.
- History of malignancy, with the exception of adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix.
- Any active uncontrolled viral, bacterial, fungal, endoparasitic, or opportunistic infection.
- Serological positivity to HCV or HIV
- Patients who are unwilling to practice pharmacological prophylaxis in case of HBsAg or HBcAb positivity
- Receipt of live or live-attenuated vaccines within 6 weeks of randomization.
- Presence or history of Child-Pugh score B and C hepatic cirrhosis.
- Hepatic disease with the presence at two consecutive assessments 15 days apart of either of the following: total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or alanine aminotransferase or aspartate aminotransferase ≥ 3.0 times the ULN.
- Presence or history of clinically significant cardiac disease (including coronary artery disease, moderate to severe valve stenosis or insufficiency, symptomatic mitral valve prolapse, presence of prosthetic mitral or aortic valve).
- Left ventricular ejection fraction (LVEF) < 50%.
- eGFR < 60 mL/min/1.73m2
- Forced expiratory volume in one second (FEV1) <70% predicted (no bronchodilator).
- Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) < 70% predicted
- Known untreated or unregulated thyroid disease.
- Positive pregnancy test or breast-feeding.
- Patients who are unwilling to practice adequate contraception during the duration of the study. Female participants of child-bearing potential should use highly effective contraception for 12 months after AHSCT, 4 months after the last infusion of alemtuzumab and for the entire time of natalizumab, ocrelizumab, ofatumumab and ublituximab treatment. Female highly effective contraception methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable implantable); Intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner; sexual abstinence. Male participants with female partners of child-bearing potential must be willing to use highly effective contraception if they are randomized to the AHSCT arm for 12 months after treatment. Male highly effective contraception methods include: vasectomy, sexual abstinence or the use of male condom with or without spermicide plus one highly effective contraception method for the female partner.
- Prior history of solid organ transplantation.
- Prior history of AHSCT.
- Prior exposure to mitoxantrone.
- Prior exposure to cyclophosphamide.
- Inability to understand the contents of the Informed Consent form.
- Failure to willingly accept or comprehend risk of irreversible sterility as a side effect of therapy.
- Any condition that precludes the participant from undergoing MRI with gadolinium administration.
- Presence or history of genetically inherited progressive central nervous system disorder, or central nervous system tumors.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary outcome is the occurrence of any evidence of multiple sclerosis disease activity (NEDA-3) over 36 months, analyzed as time-to-event [Time frame: from randomization up to 36 months post randomization]
Secondary endpoints 37
- The proportion of participants who experience a serious adverse event [Time frame: from randomization up to 36 months post randomization]
- The proportion of participants who experience a serious late adverse event [Time frame: from day 100 post AHSCT up to 36 months post randomization].
- The annual relapse rate at 12, 24 and 36 months
- The incidence of 6 months confirmed disability improvement as measured by the EDSS over 36 months
- The prevalence of disability improvement over 36 months
- The proportion of patients who have confirmed disability improvement, confirmed stable EDSS or confirmed disability progression at 12, 24 and 36 months
- The incidence of 6 months confirmed progression on hand/arm function as measured by the 9HPT over 36 months
- The incidence of 6 months confirmed progression on ambulation as measured by the T25FW test over 36 months
- Number of new brain lesions at 12, 24 and 36 months
- Number of gadolinium-enhancing brain lesions at 12, 24 and 36 months
- Changes in whole brain volume at 12, 24 and 36 months
- The proportion of patients with no evidence of disease activity including atrophy (NEDA-4) at 12, 24 and 36 months
- Changes in MRI T2-weighted hyperintense lesion volume over 36 months
- Changes in MRI T1-weighted hypointense lesion volume over 36 months
- Changes in BICAMS z-scores at 12, 24 and 36 months
- Changes in MSFC z-scores at 12, 24 and 36 months
- Changes in serum neurofilament light chain concentration at 12, 24 and 36 months
- Changes in the IgG/IgM index in the cerebrospinal fluid at 36 months
- Presence of oligoclonal bands in the cerebrospinal fluid at 36 months
- Changes in the 2.5 low contrast visual acuity at 12, 24 and 36 months
- Changes in the peripheral retinal nerve fiber layer thickness assessed by optical coherence tomography at 12, 24 and 36 months
- Changes in the retinal inner nuclear layer thickness assessed by optical coherence tomography at 12, 24 and 36 months
- Changes in the Multiple Sclerosis Impact Scale at 12, 24 and 36 months
- Changes in Multiple Sclerosis Walking Scale over at 12, 24 and 36 months
- Changes in the Modified Fatigue Impact Scale at 12, 24 and 36 months
- Changes in the WHO-QOL-Bref and the EuroQoL EQ-5D at 12, 24 and 36 months
- All-cause mortality over 36 months
- Proportion of participants who develop secondary autoimmune diseases over 36 months
- Time to neutrophil engraftment among AHSCT recipients
- Proportion of AHSCT recipients who experience primary or secondary graft failure
- Percentage of female patients who experiences amenorrhoea during the study period
- Percentage of female patients of child-bearing potential who maintains or resumes regular menstruation
- Time to resumption of spontaneous menses after AHSCT and/or interruption of hormonal contraception
- Variation in ovarian reserve parameters (anti-mullerian hormone levels and antral follicular count) over 36 months
- Variation in sperm count, motility and morphology over 36 months
- Percentage of pregnancy within 12 months of attempts among patients that will try to conceive after AHSCT [Time frame: from day 365 post AHSCT up to 36 months post randomization].
- Number of new cervical spinal cord T2 lesions and of T1 gadolinium-enhancing lesions at 36 months.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 16
Rabbit Anti-Human Thymocyte Immunoglobulin
SUB30326 · Substance
- Active substance
- Rabbit Anti-Human Thymocyte Immunoglobulin
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 2.5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Anti-Human T-Lymphocyte Immunoglobulin From Rabbits
SUB21246 · Substance
- Active substance
- Anti-Human T-Lymphocyte Immunoglobulin From Rabbits
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 2.5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 4 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 4 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4 mg/m2 milligram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 4 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07627MIG · Substance
- Active substance
- Filgrastim
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 10 µg/Kg microgram(s)/kilogram
- Max total dose
- 10 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07627MIG · Substance
- Active substance
- Filgrastim
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 10 µg/Kg microgram(s)/kilogram
- Max total dose
- 10 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06132MIG · Substance
- Active substance
- Carmustine
- Pharmaceutical form
- POWDER AND SOLVENT FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06132MIG · Substance
- Active substance
- Carmustine
- Pharmaceutical form
- POWDER AND SOLVENT FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06132MIG · Substance
- Active substance
- Carmustine
- Pharmaceutical form
- POWDER AND SOLVENT FOR CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 300 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB192476 · Substance
- Active substance
- Melphalan Flufenamide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 140 mg/m2 milligram(s)/sq. meter
- Max total dose
- 140 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07337MIG · Substance
- Active substance
- Etoposide
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 200 mg/m2 milligram(s)/sq. meter
- Max total dose
- 200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 200 ml/cm2 millilitre(s)/square cm
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 5
Tysabri 300 mg concentrate for solution for infusion
PRD10194542 · Product
- Active substance
- Natalizumab
- Substance synonyms
- AN100226M
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AG03 — -
- Marketing authorisation
- EU/1/06/346/001
- MA holder
- BIOGEN NETHERLANDS B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Ocrevus 300 mg concentrate for solution for infusion
PRD5771848 · Product
- Active substance
- Ocrelizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AA36 — -
- Marketing authorisation
- EU/1/17/1231/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB182428 · Substance
- Active substance
- Ublituximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 450 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 60 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Kesimpta 20 mg solution for injection in pre-filled pen
PRD8833244 · Product
- Active substance
- Ofatumumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 60 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AG12 — -
- Marketing authorisation
- EU/1/21/1532/004
- MA holder
- NOVARTIS IRELAND LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
LEMTRADA 12 mg concentrate for solution for infusion
PRD3337642 · Product
- Active substance
- Alemtuzumab
- Substance synonyms
- CAMPATH-1H, CAMPATH-1
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS DRIP USE
- Max daily dose
- 12 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AG06 — -
- Marketing authorisation
- EU/1/13/869/001
- MA holder
- SANOFI BELGIUM
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Sponsor organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Address
- Via Operai 40
- City
- Genoa
- Postcode
- 16149
- Country
- Italy
Scientific contact point
- Organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Contact name
- Gabriele Dati
Public contact point
- Organisation
- Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S
- Contact name
- DIGINOMI - Università di Genova
Locations
1 EU/EEA country · 8 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 90 | 8 |
| Rest of world | — | 0 | — |
Investigational sites
Careggi University Hospital
SOD di Neurologia 1, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
SCDO Neurologia, Regione Gonzole 10, 10043, Orbassano
ARNAS Civico Di Cristina Benfratelli
UU.OO Neurologia con Stroke Unit, Piazza Nicola Leotta 4, 90127, Palermo
Azienda Unita Sanitaria Locale Della Romagna
U.O. Neurologia di Ravenna, Viale Vincenzo Randi 5, 48121, Ravenna
Istituto San Raffaele
UO Neurologia, Via Olgettina 58, 20132, Milan
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOC di Neurologia, Largo Francesco Vito 1, 00168, Rome
IRCCS Ospedale Policlinico San Martino
Clinica Neurologica UO 26, Largo Rosanna Benzi 10, 16132, Genoa
Careggi University Hospital
SOD Neurologia D'urgenza, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-10-31 | 2024-10-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 40 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocollo 2024-515470-26-00_Redacted | 2.1 |
| Protocol (for publication) | D2_NET_MS Protocol modification n 2 2024-515470-26-00_Redacted | 2 |
| Recruitment arrangements (for publication) | K1_ NET-MS Recruitment arrangements v1 | 1.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Privacy Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_ICF patient _Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF _dummy_run_ Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS patient _ Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L2_1 NET-MS GP Letter v2 Clean | 2.0 |
| Subject information and informed consent form (for publication) | L2_2 NET-MS Emergency_card_patient v2 Clean_Redacted | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_10 RCP Ocrelizumab | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_11 RCP Ofatumumab Kesimpta | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_12 RCP Ublituximab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_4 Carmustina 50 e 300 mg Gazzetta n 152 del 1 luglio 2022 - AIFA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_4 RCP_Carmustina medac | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_8 RCP Natilizumab | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_9 RCP Alemtuzumab | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Accofil | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP BICNU | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Citarabina ACCORD | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Citarabina HIKMA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Citarabina Pfizer | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Endoxan Baxter | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Etoposide ACCORD | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Etoposide SANDOZ | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Etoposide TEVA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Grafalon | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Granulokine_002317_027772 | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP grastofil | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP melphalan | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Nivestim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP OBVIUS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Ratiograstim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Tevagrastim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Thymoglobuline | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_RCP Zarzio | 1 |
| Synopsis of the protocol (for publication) | D1_NET_MS Protocol Lay Summary_ITA 2024-515470-26-00 v1 | 1.0 |
| Synopsis of the protocol (for publication) | D1_NET_MS Protocol Synopsis_ITA 2024-515470-26-00 v2_1 Clean | 2.1 |
| Synopsis of the protocol (for publication) | D1_NET-MS D1_Protocol Synopsis_ENG 2024-515470-26-00 v2_1 Clean | 2.1 |
| Synopsis of the protocol (for publication) | D1_NET-MS D1_Protocol Synopsis_ENG 2024-515470-26-00 v2_1 TC | 2.1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-10 | Italy | Acceptable 2024-10-31
|
2024-12-09 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-19 | Italy | Acceptable 2025-07-29
|
2025-08-27 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-10-13 | Italy | Acceptable | 2025-11-17 |