A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis

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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WA39085 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Italy
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea; UOC Neurologia
    • Roma, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
• Poland
  • Gda?sk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne; Klinika Neurologii Rozwojowej
  • Pozna?, Poland, 60-355
    • Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
  • Warszawa, Poland, 02-091
    • Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego; Klinika Neurologii Dzieciecej
  • Warszawa, Poland, 04-730
    • Instytut Pomnik Centrum Zdrowia Dziecka; Klinika Neurologii i Epileptologii
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Childrens National Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Universtiy school of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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	Drug: Ocrelizumab; 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
Experimental: Cohort 2; 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	Drug: Ocrelizumab; 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
Experimental: Cohort 3 (optional); 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	Drug: Ocrelizumab; 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
Experimental: Cohort 4 (optional); 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	Drug: Ocrelizumab; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum Concentration of Ocrelizumab	6 months, Up to 5 years
Levels of CD19+ B-cell Count in Blood	6 months, Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with Adverse Events	Severity of adverse events is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	6 months, Up to 5 years
Level of Circulating White Blood Cells (WBC)	WBC include B cells, T cells, natural killer (NK) cells and other leukocytes	6 months, Up to 5 years
Developmental Milestones - Growth velocity: Height. Change in height measured in centimeters (cm)		6 months, Up to 5 years
Developmental Milestones: Bone age assessment by wrist/hand radiographs	Bone age should be reported according to the Greulich and Pyle Atlas (Greulich and Pyle, 1959)	6 months, Up to 5 years
Developmental Milestones: Male and female puberty assessed by Tanner staging	Tanner stages (stages 1 to 5) (Tanner, 1986)	6 months, Up to 5 years
Developmental Milestones: Age at menarche, related with the female reproductive status	This milestone is recorded as date of menarche (day, month, year)	6 months, Up to 5 years
Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)		6 months, Up to 5 years
Levels of Blood Immunoglobulins		6 months, Up to 5 years
Antibody Titers Against Standard Vaccines	Measurement of antibody titers to common antigens (mumps, rubella, varicella, S. pneumoniae)	6 months, Up to 5 years
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Ocrelizumab		6 months, Up to 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): October 5, 2023
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: WA39085; 2016-002667-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No