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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04075266
Collaborator
(none)
36
Enrollment
23
Locations
4
Arms
84.1
Anticipated Duration (Months)
1.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 9, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Jan 12, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Serum Concentration of Ocrelizumab [6 months, Up to 5 years]

  2. Levels of CD19+ B-cell Count in Blood [6 months, Up to 5 years]

Secondary Outcome Measures

  1. Proportion of Participants with Adverse Events [6 months, Up to 5 years]

    Severity of adverse events is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  2. Level of Circulating White Blood Cells (WBC) [6 months, Up to 5 years]

    WBC include B cells, T cells, natural killer (NK) cells and other leukocytes

  3. Developmental Milestones - Growth velocity: Height. Change in height measured in centimeters (cm) [6 months, Up to 5 years]

  4. Developmental Milestones: Bone age assessment by wrist/hand radiographs [6 months, Up to 5 years]

    Bone age should be reported according to the Greulich and Pyle Atlas (Greulich and Pyle, 1959)

  5. Developmental Milestones: Male and female puberty assessed by Tanner staging [6 months, Up to 5 years]

    Tanner stages (stages 1 to 5) (Tanner, 1986)

  6. Developmental Milestones: Age at menarche, related with the female reproductive status [6 months, Up to 5 years]

    This milestone is recorded as date of menarche (day, month, year)

  7. Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI) [6 months, Up to 5 years]

  8. Levels of Blood Immunoglobulins [6 months, Up to 5 years]

  9. Antibody Titers Against Standard Vaccines [6 months, Up to 5 years]

    Measurement of antibody titers to common antigens (mumps, rubella, varicella, S. pneumoniae)

  10. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Ocrelizumab [6 months, Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
10 Years to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Loma Linda University health Loma Linda California United States 92354
2 University of California San Francisco San Francisco California United States 94117
3 University of Colorado Denver Childrens Hospital Rocky Mountain MS Center Aurora Colorado United States 80045
4 Childrens National Health Center Washington District of Columbia United States 20010
5 University of Louisville Physicians Louisville Kentucky United States 40202
6 Boston Childrens Hospital Boston Massachusetts United States 02115
7 Washington Universtiy school of Medicine Saint Louis Missouri United States 63110
8 Pediatric MS Center at New York University Langone Medical Center New York New York United States 10016
9 Stony Brook University Medical Center Stony Brook New York United States 11794
10 Akron Childrens Hospital Akron Ohio United States 44308
11 Cleveland Clinic Cleveland Ohio United States 44106
12 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
13 Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia Roma Lazio Italy 00165
14 Azienda Ospedaliera Sant'Andrea; UOC Neurologia Roma Lazio Italy 00189
15 Irccs A.O.U.San Martino Ist; Dinogmi Genova Liguria Italy 16132
16 Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico Gallarate Lombardia Italy 21013
17 IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla Milano Lombardia Italy 20132
18 AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla Catania Sicilia Italy 95123
19 Uniwersyteckie Centrum Kliniczne; Klinika Neurologii Rozwojowej Gdańsk Poland 80-952
20 Szpital Kliniczny im. H. Swiecickiego U.M. w Poznaniu; Od. Kliniczny Neurologii Dzieci i Młodziezy Poznań Poland 60-355
21 Dziecięcy Szpital Kliniczny im. Józefa Polikarpa Brudzińskiego; Klinika Neurologii Dzieciecej Warszawa Poland 02-091
22 Instytut Pomnik Centrum Zdrowia Dziecka; Klinika Neurologii i Epileptologii Warszawa Poland 04-730
23 Instytut Centrum Zdrowia Matki Polki; Klinika Neurologii Łódź Poland 93-338

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04075266
Other Study ID Numbers:
  • WA39085
  • 2016-002667-34
First Posted:
Aug 30, 2019
Last Update Posted:
Aug 3, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Ocrelizumab

Study Results

No Results Posted as of Aug 3, 2022