Clinical trial NCT04075266: A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
Official title: An Open-Label, Parallel-Group Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Sclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-08-30
Enrollment: 23
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2-year study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic (PD) effects of ocrelizumab in children and adolescents ages ≥ 10 to ≤ 18 years with relapsing-remitting multiple sclerosis (RRMS). The data from this study will serve to determine the dosing regimen of ocrelizumab to be further investigated in the subsequent Phase III study in children and adolescents.


Eligibility criteria: Inclusion Criteria:

* Body weight \>/= 25 kg
* Children and adolescents must have received all childhood required vaccinations
* Female participants of childbearing potential must agree to either remain completely abstinent or to use reliable means of contraception
* Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
* Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
* Neurologic stability for \>/= 30 days prior to screening, and between screening and baseline
* Participants naive to prior disease-modifying therapy (DMT)
* Participants 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

Exclusion Criteria:

* Known presence or suspicion of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis, neuromyelitis optica or neuromyelitis optica spectrum disorders and any neurologic, somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development
* Patients that are aquaporin 4 positive and myelin oligodendrocyte glycoprotein (MOG) antibody positive are not eligible to participate in the study.
* In case of an ADEM-like appearance of the first MS attack, a second attack with clear MS-like features is required.
* Infection requiring hospitalization or treatment with IV anti-infective agents
* History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation
* History or laboratory evidence of coagulation disorders
* Peripheral venous access that precludes IV administration and venous blood sampling
* Inability to complete a magnetic resonance imaging (MRI) scan
* History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
* History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody (mAbs) or known hypersensitivity to any component of ocrelizumab solution
* Previous treatment with B-cell-targeted therapies
* Percentage of CD4 \< 30%
* Absolute Neutrophil Count \< 1.5x1000/microliter
* Lymphocyte count below the lower limit of normal (LLN) for age- and sex-specific reference range

Primary outcomes:
measure: Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab
timeFrame: Pre-dose 5- 30 minutes and post-dose 30 mins on Days 1, 15 and 169; At any time on Days 29, 57, 85 and 113
measure: Dose Exploration Period: Maximum Concentration (Cmax) of Ocrelizumab
timeFrame: Pre-dose 5- 30 minutes and post-dose 30 mins on Days 1, 15 and 169; At any time on Days 29, 57, 85 and 113
measure: Dose Exploration Period: Levels of CD 19+ B-cell Count in Blood
timeFrame: At Week 24
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 7 years
measure: Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells
timeFrame: At Week 24
measure: OOE Period: Level of Circulating T Cells and NK Cells
timeFrame: Up to 5 years
measure: Dose Exploration Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
timeFrame: At Week 24
measure: OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
timeFrame: Up to 5 years
measure: Developmental Milestones - Growth Velocity: Change in Height
timeFrame: Up to 7 years
measure: Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs
timeFrame: Up to 7 years
measure: Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging
timeFrame: Up to 7 years
measure: Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status
timeFrame: Up to 7 years
measure: Dose Exploration Period: Number of Participants With Shift From Baseline in Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)
timeFrame: Up to Week 24
measure: OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI
timeFrame: Up to 5 years
measure: Dose Exploration Period: Levels of Blood Immunoglobulins
timeFrame: At Week 24
measure: OOE Period: Levels of Blood Immunoglobulins
timeFrame: Up to 5 years
measure: Dose Exploration Period: Number of Participants With Antibody Titers Against Standard Vaccines
timeFrame: At Week 24
measure: OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines
timeFrame: Up to 5 years
measure: Dose Exploration Period: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
timeFrame: At Week 24
measure: OOE Period: Number of Participants With ADAs to Ocrelizumab
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
state: Colorado
city: Washington
country: United States
facility: Childrens National Health Center
state: District of Columbia
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington Universtiy school of Medicine
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
state: Lazio
city: Catania
country: Italy
facility: AOU Policlinico V. Emanuele - P.O G. Rodolico
state: Sicilia
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Pozna?
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: