Multiple SclerosisPhase 2NCT04075266
A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
A Phase 2 study testing Ocrelizumab in people with Multiple Sclerosis, run by Hoffmann-La Roche at 12 sites in 3 countries.
Trial summary
This 12-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). Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 9 Jan 2020to 26 Apr 2032
- Phase
- Phase 2
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 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age at screening between =/>10 to <18 years
- 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
- 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
Who cannot join
- 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 acute disseminated encephalomyelitis (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
Show all 15Show fewer
- 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
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
United States5 sites
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
Aurora, Colorado, 80045
Boston Childrens Hospital
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
Washington Universtiy school of Medicine
St Louis, Missouri, 63110
Childrens National Health Center
Washington D.C., District of Columbia, 20010
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gda?sk, 80-952
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, 60-355
Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
Warsaw, 02-091
Instytut Pomnik Centrum Zdrowia Dziecka
Warsaw, 04-730
Italy3 sites
AOU Policlinico V. Emanuele - P.O G. Rodolico
Catania, Sicily, 95123
Ospedale Pediatrico Bambino Gesù
Rome, Lazio, 00165
Azienda Ospedaliera Sant'Andrea
Rome, Lazio, 00189
About this study
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
This 12-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.
- Conditions
- Multiple Sclerosis
- Being tested
- Ocrelizumab
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OcrelizumabDrug
Ocrelizumab is administered as two infusions of half the dose given 14 days apart for the first dose, then subsequent doses are administered as a single infusion every 24 weeks.
Cohort 1: total dose of 300 mg Cohort 2: total dose of 600 mg Cohort 3 and 4: additional dose level(s) may be lower than 300 mg, between 300 mg and 600 mg, or higher than 600 mg, but will be no higher than 1200 mg
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants with a body weight from >/= 25 kg to < 40 kg (with at least 2 participants with a body weight from >/= 25 kg to </= 35 kg) will receive 300 milligram (mg) ocrelizumab Receives: Drug: Ocrelizumab |
| Cohort 2 | Experimental | Participants with a body weight >/= 40 kg (with at least 2 participants with a body weight >/= 40 kg but </= 50 kg) will receive 600 mg ocrelizumab Receives: Drug: Ocrelizumab |
| Cohort 3 (optional) | Experimental | Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight from >/= 25 kg to < 40 kg may be enrolled and receive another dose level of ocrelizumab Receives: Drug: Ocrelizumab |
| Cohort 4 (optional) | Experimental | Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight >/= 40 kg may be enrolled and receive another dose level of ocrelizumab Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab
The population PK model was used to simulate concentration-time course and predict individual area under the concentration versus time curve. The data for the PK parameter: area under the concentration versus time curve was collected and analyzed as per body weight range (<40kg to ≥40 kg).
Measured: 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
Dose Exploration Period: Maximum Concentration (Cmax) of Ocrelizumab
The population PK model was used to simulate concentration-time course and predict individual Cmax. The data for the PK parameter: Cmax was collected and analyzed as per body weight range (<40kg to ≥40 kg).
Measured: 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
Dose Exploration Period: Levels of CD 19+ B-cell Count in Blood
Measured: At Week 24
Secondary outcomes (17)
Number of Participants With Adverse Events (AEs)
An AE is untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Measured: Up to 12 years
Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells
Measured: At Week 24
OOE Period: Level of Circulating T Cells and NK Cells
Measured: Up to 12 years
Dose Exploration Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
Measured: At Week 24
OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
Measured: Up to 12 years
Developmental Milestones - Growth Velocity: Change in Height
Measured: Up to 12 years
Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs
Measured: Up to 12 years
Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging
Measured: Up to 12 years
Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status
Measured: Up to 12 years
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)
The change in the non-MS CNS pathology was assessed using MRI scans.
Measured: Up to Week 24
OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI
Measured: Up to 12 years
Dose Exploration Period: Levels of Blood Immunoglobulins
Measured: At Week 24
OOE Period: Levels of Blood Immunoglobulins
Measured: Up to 12 years
Dose Exploration Period: Number of Participants With Antibody Titers Against Standard Vaccines
Measurement of antibody titers to common antigens (mumps, rubella, varicella, and Streptococcus pneumoniae [S. pneumoniae]) were performed.
Measured: At Week 24
OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines
Measured: Up to 12 years
Dose Exploration Period: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
Measured: At Week 24
OOE Period: Number of Participants With ADAs to Ocrelizumab
Measured: Up to 12 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start9 Jan 2020
- Primary completion5 Oct 2023
- Study completion26 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04075266
- Sponsor's protocol ID
- WA39085
- Other IDs
- 2016-002667-34, 2016
- Status last verified
- Aug 2026
- First submitted
- 14 Aug 2019
- Last updated
- 14 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
Mar S, Valeriani M, Steinborn B, Schreiner T, Waubant E, Filippi M, Kotulska K, Mazurkiewicz-Beldzinska M, El Azzouzi B, Lin CJ, Shen YA, Kletzl H, Evershed J, Hogea A, Manlius C, Bonati U, Banwell B. Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study. J Neurol. 2025 Jan 15;272(2):137. doi: 10.1007/s00415-024-12879-z.
PubMed 39812825