Relapsing-Remitting multiple sclerose
Conditions
Interventions
Group A gets ocrelizumab, which is given every 6 months by infusion (a fluid
given slowly in your vein in your arm). The first dose is given as two
infusions of half the dose of ocrelizumab on Days
Sponsors
Hoffmann-La Roche
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: • Informed consent for study participation signed by the parents or a legal guardian, with patient assent obtained verbally and when possible, in writing, from all pediatric patients old enough to fully comprehend the assent document prior to any study-specific screening procedures, as per local requirements • Able to comply with the study protocol, in the investigator's judgment Patients who are unable to complete exploratory assessments (e.g., SDMT or questionnaires) due to physical/disease limitations will not be excluded from the study. • Age between >= 10 to = 25 kg • Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases. Patients negative for serological testing for varicella zoster will have the full course of the vaccine for chickenpox completed before study start, except patients who have already received the full course of the vaccine for chickenpox, depending on local regulations. • For female patients of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Female patients must remain abstinent or use two methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 24 weeks after the final dose of ocrelizumab/ocrelizumab placebo and for 2 months after the final dose of fingolimod/fingolimod placebo. Adherence to local requirement, if more stringent, is required. A female is considered to be of childbearing potential if she is postmenarcheal and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of < 1% per year include the following: o Established hormonal contraception: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) o Intrauterine devices: intrauterine device, intrauterine hormone-releasing system, and copper intrauterine device A barrier method may be used as the second contraceptive method, such as the following: o A male or female condom with or without spermicide o A cap, diaphragm, or sponge with spermicide The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. If required per local guidelines or regulations, locally recognized acceptable methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. Inclusion Criteria Related to Pediatric Multiple Scl
Exclusion criteria
Exclusion criteria: While participating in this study, patients are not allowed to take part in other investigational research projects involving administration of any drug or substance or involving any procedure that would place patients at risk or could jeopardize this study results. Exclusions Related to General Health Patients who meet any of the following criteria related to general health will be excluded from study entry: • Pregnancy or lactation • Known presence or suspicion (based on clinical or laboratory parameters) of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica or neuromyelitis optica spectrum disorders; and any neurological (other than MS), somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development In case of an ADEM like appearance of the first MS relapse, a second relapse with clear MS like features is required. • Patients that are aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive at screening • Clinical or laboratory findings at first presentation not typically for MS, such as signs of infection; signs of encephalopathy such as confusion, convulsion, reduced state of consciousness. • Abnormal findings in the cerebrospinal fluid (CSF) at first MS presentation. Protein * 100 mg/dL. Pleocytosis * 50 cells/mm3. Presence of neutrophils or eosinophils above the normal reference range per local laboratory, or atypical cells. Note: CSF sampling is not mandated at screening and may be performed at investigator discretion to confirm diagnosis of pediatric RRMS. • Atypical MRI findings: ADEM like presentation of lesions; lesions in atypical location for MS; bilateral optic neuritis; extensive spinal cord lesions (* 3 spinal segments) • Significant uncontrolled somatic diseases or any other significant condition that may preclude patient from participating in the study • Known active bacterial, viral, fungal, mycobacterial infection, or other infection, excluding fungal infection of nail beds • Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to Day 1 visit or oral anti-infective agents within 2 weeks prior to Day 1 visit • History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis) • Receipt of any type of vaccine (e.g. live, live-attenuated vaccine, non-live) within 6 weeks prior to treatment allocation. The patient's vaccination record and a need for immunization should be carefully reviewed (scheduled vaccinations should be completed at least 6 weeks prior to receiving ocrelizumab, as per local guidelines). • History or laboratory (local laboratory test) evidence of clinically significant coagulation disorders (e.g., any coagulation disorder requiring medical treatment). • Peripheral venous access that precludes IV administration and venous blood sampling as required per study protocol • Inability to complete an MRI scan (e.g., due to weight, claustrophobia, hypersensitivity to gadolinium, cochlear implants, presence of foreign substances in the eye, or intracranial vascular clips) • Teeth braces interfering with MRI acquisition • History of cancer, including solid tumors, hematol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| primary endpoint to primary objective is: • Protocol-defined annualized relapse rate (ARR) The comparison of interest is the difference of protocol-defined ARR, as measured through the rate ratio in counts during the double-blind period. The primary comparison will be made in the hypothetical situation that patients do not withdraw from the study treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| secondary endpoints to secondary objectives are: - Number of new or enlarging T2-hyperintense lesions (T2 lesions) as detected by brain MRI during the double-blind period - Protocol-defined ARR by Week 96 - Number of T1 Gd lesions at Week 12 - Number of new or enlarging T2 lesions during the double-blind period - Protocol-defined ARR during the double-blind period All comparisons will be made in the hypothetical situation that patients do not withdraw from the study treatment. exploratory endpoints to exploratory objectives are: • Time to the first relapse (Kaplan-Meier proportion of relapse-free patients) • Time to the first new or enlarging T2 lesions (Kaplan-Meier proportion of patients free of new or enlarging T2 lesions) • Change in total T2 lesion volume from baseline to Weeks 24, 48 and 96 • Change in total T1-hypointense lesion (T1 lesion) volume from baseline to Weeks 24, 48, and 96 • Change in the Symbol Digit Modalities Test (SDMT) from baseline to Weeks 48 and 96 • Time to 24-week confirmed 4-point worsening in the SDMT • Annual rate of change from baseline in the EDSS during the double-blind period • Time to confirmed disability progression over the treatment period, defined as an increase of * 1.0 point from baseline EDSS when the baseline score is * 5.5. EDSS will be confirmed at a regular scheduled visit at least 12 weeks or 24 weeks after the initial documentation of neurological worsening. • Change in patient- and caregiver-reported Pediatric Quality of Life Inventory* (PedsQL*) Generic Core Scale, Version 4.0, from baseline to Weeks 48 and 96 • Change in patient-reported fatigue, as measured by the PedsQL Multidimensional Fatigue Scale (domain scores and total score) from baseline to Week 48 and 96 • Change in EQ-5D-5L from baseline to Weeks 48 and 96 • Patient Global Impression of Change (PGIC) for fatigue, cognition, and overall MS symptoms at Weeks 48 and 96 • Caregiver Global Impression of Change (CaGI-C) for | — |
Countries
Netherlands
Outcome results
None listed