Back to resultsA Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ocrelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
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
Sites / Locations
- Loma Linda University health
- University of California San Francisco
- University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
- Childrens National Health CenterRecruiting
- University of Louisville Physicians
- Boston Childrens HospitalRecruiting
- Washington Universtiy school of Medicine
- Pediatric MS Center at New York University Langone Medical Center
- Stony Brook University Medical Center
- Akron Childrens Hospital
- Cleveland Clinic
- The Children's Hospital of Philadelphia
- Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia
- Azienda Ospedaliera Sant'Andrea; UOC NeurologiaRecruiting
- Irccs A.O.U.San Martino Ist; DinogmiRecruiting
- Ospedale S.Antonio Abate; Neurologia 2 ? Sclerosi Multipla e Recupero Neurologico
- IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
- AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
- Clinstile S.A de C.V.
- Instytut Centrum Zdrowia Matki Polki; Klinika Neurologii
- Uniwersyteckie Centrum Kliniczne; Klinika Neurologii Rozwojowej
- Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
- Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego; Klinika Neurologii Dzieciecej
- Instytut Pomnik Centrum Zdrowia Dziecka; Klinika Neurologii i Epileptologii
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3 (optional)
Cohort 4 (optional)
Arm Description
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
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
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
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
Outcomes
Primary Outcome Measures
Serum Concentration of Ocrelizumab
Levels of CD19+ B-cell Count in Blood
Secondary Outcome Measures
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
Level of Circulating White Blood Cells (WBC)
WBC include B cells, T cells, natural killer (NK) cells and other leukocytes
Developmental Milestones - Growth velocity: Height. Change in height measured in centimeters (cm)
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)
Developmental Milestones: Male and female puberty assessed by Tanner staging
Tanner stages (stages 1 to 5) (Tanner, 1986)
Developmental Milestones: Age at menarche, related with the female reproductive status
This milestone is recorded as date of menarche (day, month, year)
Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)
Levels of Blood Immunoglobulins
Antibody Titers Against Standard Vaccines
Measurement of antibody titers to common antigens (mumps, rubella, varicella, S. pneumoniae)
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Ocrelizumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04075266
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 9, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 1, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 3 (optional)
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 4 (optional)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ocrelizumab
Intervention Description
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
Primary Outcome Measure Information:
Title
Serum Concentration of Ocrelizumab
Time Frame
6 months, Up to 5 years
Title
Levels of CD19+ B-cell Count in Blood
Time Frame
6 months, Up to 5 years
Secondary Outcome Measure Information:
Title
Proportion of Participants with Adverse Events
Description
Severity of adverse events is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time Frame
6 months, Up to 5 years
Title
Level of Circulating White Blood Cells (WBC)
Description
WBC include B cells, T cells, natural killer (NK) cells and other leukocytes
Time Frame
6 months, Up to 5 years
Title
Developmental Milestones - Growth velocity: Height. Change in height measured in centimeters (cm)
Time Frame
6 months, Up to 5 years
Title
Developmental Milestones: Bone age assessment by wrist/hand radiographs
Description
Bone age should be reported according to the Greulich and Pyle Atlas (Greulich and Pyle, 1959)
Time Frame
6 months, Up to 5 years
Title
Developmental Milestones: Male and female puberty assessed by Tanner staging
Description
Tanner stages (stages 1 to 5) (Tanner, 1986)
Time Frame
6 months, Up to 5 years
Title
Developmental Milestones: Age at menarche, related with the female reproductive status
Description
This milestone is recorded as date of menarche (day, month, year)
Time Frame
6 months, Up to 5 years
Title
Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)
Time Frame
6 months, Up to 5 years
Title
Levels of Blood Immunoglobulins
Time Frame
6 months, Up to 5 years
Title
Antibody Titers Against Standard Vaccines
Description
Measurement of antibody titers to common antigens (mumps, rubella, varicella, S. pneumoniae)
Time Frame
6 months, Up to 5 years
Title
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Ocrelizumab
Time Frame
6 months, Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: WA39085 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Loma Linda University health
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Childrens National Health Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Louisville Physicians
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Withdrawn
Facility Name
Boston Childrens Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington Universtiy school of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Pediatric MS Center at New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Withdrawn
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Individual Site Status
Withdrawn
Facility Name
Akron Childrens Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Individual Site Status
Withdrawn
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Withdrawn
Facility Name
Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Azienda Ospedaliera Sant'Andrea; UOC Neurologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00189
Country
Italy
Individual Site Status
Recruiting
Facility Name
Irccs A.O.U.San Martino Ist; Dinogmi
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ospedale S.Antonio Abate; Neurologia 2 ? Sclerosi Multipla e Recupero Neurologico
City
Gallarate
State/Province
Lombardia
ZIP/Postal Code
21013
Country
Italy
Individual Site Status
Withdrawn
Facility Name
IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95123
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Clinstile S.A de C.V.
City
Mexico City
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
06700
Country
Mexico
Individual Site Status
Withdrawn
Facility Name
Instytut Centrum Zdrowia Matki Polki; Klinika Neurologii
City
?ód?
ZIP/Postal Code
93-338
Country
Poland
Individual Site Status
Withdrawn
Facility Name
Uniwersyteckie Centrum Kliniczne; Klinika Neurologii Rozwojowej
City
Gda?sk
ZIP/Postal Code
80-952
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
City
Pozna?
ZIP/Postal Code
60-355
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego; Klinika Neurologii Dzieciecej
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Instytut Pomnik Centrum Zdrowia Dziecka; Klinika Neurologii i Epileptologii
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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).
Learn more about this trial
A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
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