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

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04075266
• Other study ID #: WA39085
• Secondary ID: 2016-002667-34
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 9, 2020
• Est. completion date: December 1, 2029

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: December 1, 2029
• Est. primary completion date: October 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Concentration of Ocrelizumab		6 months, Up to 5 years
Primary	Levels of CD19+ B-cell Count in Blood		6 months, Up to 5 years
Secondary	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
Secondary	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
Secondary	Developmental Milestones - Growth velocity: Height. Change in height measured in centimeters (cm)		6 months, Up to 5 years
Secondary	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
Secondary	Developmental Milestones: Male and female puberty assessed by Tanner staging	Tanner stages (stages 1 to 5) (Tanner, 1986)	6 months, Up to 5 years
Secondary	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
Secondary	Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)		6 months, Up to 5 years
Secondary	Levels of Blood Immunoglobulins		6 months, Up to 5 years
Secondary	Antibody Titers Against Standard Vaccines	Measurement of antibody titers to common antigens (mumps, rubella, varicella, S. pneumoniae)	6 months, Up to 5 years
Secondary	Percentage of Participants with Anti-Drug Antibodies (ADAs) to Ocrelizumab		6 months, Up to 5 years