A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Ocrelizumab in Children and Adolescents with Relapsing-Remitting Multiple Sclerosis

Phase 1

Conditions: Relapsing-remitting multiple sclerosis (MS)
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.1Level: LLTClassification code 10039720Term: Sclerosis multipleSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2016-002667-34-IT

Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 36

Inclusion Criteria

- Able to comply with the study protocol, in the investigator's judgment
- Age at screening between >= 10 and < 18 years
- Body weight >= 25 kg note:enrollment of Pt with a body weight>=50kg is closed
- Children and adolescents must have received all childhood required vaccinations as per local/national recommendations for childhood vaccination against infectious diseases calendar of immunization
- For female patients of childbearing potential: agreement to remain abstinent or use contraception. Adherence to local requirement, if more stringent, is required
Inclusion Criteria Related to Pediatric MS:
- Diagnosis of relapsing-remitting multiple sclerosis (RRMS) in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, Version 2012, and McDonald criteria 2017
Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
- Neurologic stability for >= 30 days prior to screening, and between screening and baseline
- Patients naïve to prior disease-modifying therapy (DMT) or patients
who have had less than a total of 6 months of DMT within the past 1 year
must have one of the following:
o At least two relapses in the last 2 years, with at least one relapse
experienced in the previous year
o At least two relapses in the last 2 years and >= 1 Gd-enhancing
lesion(s) (silent or not) on T1-weighted brain MRI at any time within the
previous year
o At least one relapse in the previous year and >= 1 Gd-enhancing
lesion(s) on T1-weighted brain MRI at any time within the last year
- Patients who have had at least 6 contiguous months of DMT within the
past 1 year must have evidence of disease activity occurring after the
full 6-month course of treatment, that is, at least one relapse or >= 1 Gd-enhancing lesion(s) on a T1-weighted brain MRI
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Excl Related to General Health:-Pregn or lactation-Known pres or suspicion of other neurol disorders that may mimic MS,includ,but not limited to,acute disseminated encephalomyelitis,andneuromyelitis optica or neuromyelitis optica spectrum disorders and any neurol,somatic or metab condit that cloud interfere with brain function or normal cognitiv or neurol develop.-Pt that are aquaporin 4 posit and myelin oligodendrocyte glycoprot(MOG)antib posit are not eligib to participate in study.-In case of ADEM-like appearance of the 1°MS attack, a 2°attack with clear MS-like feature is required.- Signif or uncontrol somatic diseases or any other signif condition that may preclude pt from participating in study-Known active bact,viral,fung,mycobacterial infect,or other infect,excluding fung infect of nail beds-Infect requiring hospit or treatm with IV anti-infectiveagents within 4 wks prior to baseline visit or oral anti-infect agents within 2 wks prior to baseline visit-History or known presence of recurrent or chronic infection(e.g.,HIV,syphilis,tuberculosis)-Receipt of a live or live-attenuated vaccine within 6 wks prior treatm allocation.Pt's vaccination record and a need forimmunization should be carefully reviewed- History or lab evidence of coagul disorders-Peripheral venous access that precludes IV administr and venous blood sampling as required per study protocol-Inability to complete an magn reson imaging(MRI)scan-Teeth braces interfering with MRI acquisition-History of cancer,including solid tumors,hemat malignancies,and carcinoma in situ(except basal cell and squamous cell carcinoma ofthe skin that have been excised and cured)-Current active alcohol or drug abuse or hist of alcohol or drug abuse.Exclus Related to Med:-Hist of a severe allergic or anaphylactic react to humanized or murine monocl antibody(mAbs)or known hypersensitivity to any component of ocreliz solution-Contraindications to or intolerance of oral or IV corticosteroids,antihistaminics,or antipyretics according to the country label-Treat with any investigational agent within 24 wks of screen or 5 half-lives,whichever is longer-Previous treatm with B-cell-targeted therapies-Any previous treatm with alemtuz, anti-CD4,cladribine,mitoxantrone,dacliz, laquinimod, total body irradiation,or bone marrow transplantation-Treatm with cyclophos, azathiop, mycophenolatemofetil,cyclospo,methotrex,or nataliz within 24 months prior to treatm alloc-Treatm with teriflun,fingolimod,or other S1P receptor modulator(e.g.,BAF312/siponimod)within 24 wks prior to treatm allocat-Treatm with fingolimod within 6 weeks prior to treatm alloc and lymphoc count<LLN for age-and sex-specif ref range treatm with any other S1P receptor modulator(e.g.BAF312/siponimod)within 24 wks prior to treatm alloc-Treatm with dimethyl fumarate within 4 wks prior to treatm alloc and lynph count <LLN for age-and sex-specific reference range-Treatm with IVIg within 12 wks prior to treatm alloc-Treatm with plasmapheresis within 4 wks prior to treatm alloc-Systemic corticost therapy within 6 wks prior to treatm alloc.Exclus Related to Lab Findings:-Posit serum beta-human chorionic growth hormone(ß-hCG)measured at screen or posit pregn test prior to first infusion of ocreliz-Posit screen tests for hepatitis B (hepat B surface antigen[HBsAg]posit, or positive hepat B core antibody[tot HBcAb]confirmed by a posit viral DNA polymerase chain reaction [PCR]) orhepatitis C antibody (HepCAb)-Posit rapid plasma reagin if confirmed

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To characterize the ocrelizumab pharmacokinetic (PK) profile in children and adolescents<br>- To evaluate relationship between drug exposure and pharmacodynamic (PD) (CD19+ B-cell count) in children and adolescents<br>;Secondary Objective: - To evaluate safety of ocrelizumab in children and adolescents<br>- To assess anti-drug antibody (ADA) development to ocrelizumab<br>;Primary end point(s): 1. Serum concentration of ocrelizumab <br>2. Levels of CD19+ B-cell count in blood ;Timepoint(s) of evaluation of this end point: 1 to 6 mounths

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Occurrence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v54.0<br>2. Change from baseline in vital signs<br>3. Change from baseline in clinical laboratory test results<br>4. Level of circulating B cells, T cells, natural killer cells, and other<br>leukocytes<br>5. Developmental milestones (e.g., growth, bone age, age at menarche, Tanner staging)<br>6. Non-MS CNS pathology as measured by brain MRI scans<br>7. Levels of blood immunoglobulins<br>8. Antibody titers against standard vaccines<br>9. Presence of ADAs during the study relative to the presence of ADAs at baseline;Timepoint(s) of evaluation of this end point: up to 48 weeks

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