A Study of Ocrelizumab in Children and Adolescents With R... | NCT04075266

NCT04075266

ID	Type	Description	Link
2016-002667-34	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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 \	Drug: Ocrelizumab
Cohort 2	Experimental	Participants with a body weight >/= 40 kg (with at least 2 participants with a body weight >/= 40 kg but \	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	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	Drug: Ocrelizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ocrelizumab	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	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).	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		At Week 24

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

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

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center		Aurora	Colorado	80045	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39812825	Derived	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ocrelizumab 300 mg	Participants who weighed between 25 kilograms (kg) to 40 kg were administered first dose of 300 milligrams (mg) ocrelizumab as two intravenous (IV) infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week optional ocrelizumab extension (OOE) period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 31, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG0006 subjects
FG00117 subjects

Safety evaluable population included all participants who received at least one dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
BG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0002187(1565 to 3090) OG0013197(1781 to 4339)

Primary

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).

PK evaluable population included all participants who were enrolled in the study.

Posted

Median

Full Range

microgram/milliters (µg/mL)

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

ID	Title	Description
OG000	Body Weight < 40 kg	Participants who weighed < 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15.
OG001	Body Weight ≥ 40 kg	Participants who weighed ≥ 40 kg were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15.

Units	Counts
Participants

Primary

Dose Exploration Period: Levels of CD 19+ B-cell Count in Blood

Safety evaluable population included all participants who received at least one dose of study drug.

Posted

Median

Full Range

cells/µL

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Units	Counts
Participants

Secondary

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.

Not Posted

Dec 2030

Up to 7 years

Participants

Secondary

Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells

Safety evaluable population included all participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

cells/microliter (µL)

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Units	Counts
Participants

Secondary

OOE Period: Level of Circulating T Cells and NK Cells

Not Posted

Dec 2030

Up to 5 years

Participants

Secondary

Dose Exploration Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte

Safety evaluable population included all participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analysis.

Posted

Mean

Standard Deviation

10^9 cells/L

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Units	Counts

Secondary

OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte

Not Posted

Dec 2030

Up to 5 years

Participants

Secondary

Developmental Milestones - Growth Velocity: Change in Height

Not Posted

Dec 2030

Up to 7 years

Participants

Secondary

Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs

Not Posted

Dec 2030

Up to 7 years

Participants

Secondary

Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging

Not Posted

Dec 2030

Up to 7 years

Participants

Secondary

Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status

Not Posted

Dec 2030

Up to 7 years

Participants

Secondary

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.

Safety evaluable population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Secondary

OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI

Not Posted

Dec 2030

Up to 5 years

Participants

Secondary

Dose Exploration Period: Levels of Blood Immunoglobulins

Safety evaluable population included all participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analysis at specified timepoint.

Posted

Mean

Standard Deviation

gram/liter (g/L)

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Units	Counts

Secondary

OOE Period: Levels of Blood Immunoglobulins

Not Posted

Dec 2030

Up to 5 years

Participants

Secondary

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.

Safety evaluable population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Secondary

OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines

Not Posted

Dec 2030

Up to 5 years

Participants

Secondary

Dose Exploration Period: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab

Posted

Count of Participants

Participants

At Week 24

ID	Title	Description
OG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.
OG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.

Units	Counts

Secondary

OOE Period: Number of Participants With ADAs to Ocrelizumab

Not Posted

Dec 2030

Up to 5 years

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ocrelizumab 300 mg	Participants who weighed between 25 kg to 40 kg were administered first dose of 300 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 150 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 300 mg was administered as a single IV infusion given 24 weeks apart.	0	6	1	6	5	6
EG001	Ocrelizumab 600 mg	Participants who weighed 40 kg or more were administered first dose of 600 mg ocrelizumab as two IV infusions given 14 days apart i. e. 2 x 300 mg on Days 1 and 15. Participants who completed the 24-week dose exploration period were eligible to continue ocrelizumab treatment in 264-week OOE period. Ocrelizumab 600 mg was administered as a single IV infusion given 24 weeks apart.	0	17	4	17	17	17

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Peripheral swelling	General disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Abscess limb	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Appendicitis	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Candida infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Gonococcal infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Pneumonia	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Alanine aminotransferase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Blood creatine phosphokinase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Dehydration	Metabolism and nutrition disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Conversion disorder	Psychiatric disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Rash	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Hypotension	Vascular disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events1 affected17 at risk
Lymphopenia	Blood and lymphatic system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Monocytopenia	Blood and lymphatic system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Neutropenia	Blood and lymphatic system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Bundle branch block left	Cardiac disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Sinus tachycardia	Cardiac disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Tachycardia	Cardiac disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Ear pain	Ear and labyrinth disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Hyperprolactinaemia	Endocrine disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Chalazion	Eye disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Eye pain	Eye disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Abdominal pain	Gastrointestinal disorders	26.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0012 events2 affected17 at risk
Abdominal pain upper	Gastrointestinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events2 affected17 at risk
Constipation	Gastrointestinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events2 affected17 at risk
Defaecation urgency	Gastrointestinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Dental caries	Gastrointestinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Diarrhoea	Gastrointestinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0014 events4 affected17 at risk
Irritable bowel syndrome	Gastrointestinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Mouth ulceration	Gastrointestinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Nausea	Gastrointestinal disorders	26.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected17 at risk
Vomiting	Gastrointestinal disorders	26.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0011 events1 affected17 at risk
Asthenia	General disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected17 at risk
Chest pain	General disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Fatigue	General disorders	26.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0014 events3 affected17 at risk
Influenza like illness	General disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Malaise	General disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Peripheral swelling	General disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Pyrexia	General disorders	26.1	Systematic Assessment	EG0005 events2 affected6 at risk EG0017 events6 affected17 at risk
Temperature intolerance	General disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Hypersensitivity	Immune system disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected17 at risk
Adenovirus infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Anal abscess	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events1 affected17 at risk
Bacterial infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Bacterial vaginosis	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
COVID-19	Infections and infestations	26.1	Systematic Assessment	EG0003 events3 affected6 at risk EG00111 events11 affected17 at risk
Fungal infection	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Gastroenteritis	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Gastrointestinal infection	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected17 at risk
Herpes virus infection	Infections and infestations	26.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected17 at risk
Herpes zoster	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected17 at risk
Influenza	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Nasal herpes	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Nasopharyngitis	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG00111 events7 affected17 at risk
Oral herpes	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Pharyngitis	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected17 at risk
Rhinitis	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events2 affected17 at risk
Tooth abscess	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Tooth infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Upper respiratory tract infection	Infections and infestations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0018 events6 affected17 at risk
Urinary tract infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events2 affected17 at risk
Viral infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events3 affected17 at risk
Viral upper respiratory tract infection	Infections and infestations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Arthropod sting	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Concussion	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Fall	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0012 events2 affected17 at risk
Immunisation reaction	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Infusion related reaction	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0005 events3 affected6 at risk EG00145 events14 affected17 at risk
Ligament rupture	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Ligament sprain	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Limb injury	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Product preparation error	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Skin laceration	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Torus fracture	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Upper limb fracture	Injury, poisoning and procedural complications	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Alanine aminotransferase increased	Investigations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected17 at risk
Aspartate aminotransferase increased	Investigations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events1 affected17 at risk
Blood alkaline phosphatase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Blood creatine phosphokinase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Blood immunoglobulin G decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Blood immunoglobulin M decreased	Investigations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected17 at risk
Blood lactate dehydrogenase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Blood triglycerides increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
CD4 lymphocytes decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
CD8 lymphocytes decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Electrocardiogram QT prolonged	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Fungal test positive	Investigations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Gamma-glutamyltransferase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
International normalised ratio increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Lipase increased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events2 affected17 at risk
Lymphocyte count decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Monocyte count decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Neutrophil count decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected17 at risk
Protein urine present	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Urine output decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Vitamin D decreased	Investigations	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Weight decreased	Investigations	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected17 at risk
Back pain	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected17 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events1 affected17 at risk
Myalgia	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events3 affected17 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Benign neoplasm of thyroid gland	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Brain fog	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Cognitive disorder	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Decreased vibratory sense	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Disturbance in attention	Nervous system disorders	26.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected17 at risk
Dizziness	Nervous system disorders	26.1	Systematic Assessment	EG0004 events2 affected6 at risk EG0015 events4 affected17 at risk
Dizziness postural	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Dysarthria	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Facial paresis	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Headache	Nervous system disorders	26.1	Systematic Assessment	EG00012 events2 affected6 at risk EG00129 events8 affected17 at risk
Hypoaesthesia	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Migraine	Nervous system disorders	26.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0015 events3 affected17 at risk
Nervous system disorder	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Paraesthesia	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected17 at risk
Presyncope	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected17 at risk
Sensory loss	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Tremor	Nervous system disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Anxiety	Psychiatric disorders	26.1	Systematic Assessment	EG0003 events1 affected6 at risk EG0014 events4 affected17 at risk
Conversion disorder	Psychiatric disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Initial insomnia	Psychiatric disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Insomnia	Psychiatric disorders	26.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0011 events1 affected17 at risk
Mood altered	Psychiatric disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Restlessness	Psychiatric disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Micturition urgency	Renal and urinary disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected17 at risk
Amenorrhoea	Reproductive system and breast disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Dysmenorrhoea	Reproductive system and breast disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events1 affected17 at risk
Cough	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0015 events5 affected17 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events2 affected17 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected17 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Acne	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected17 at risk
Erythema	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Pruritus	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected17 at risk
Psoriasis	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Rash	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Skin disorder	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Urticaria	Skin and subcutaneous tissue disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk
Wisdom teeth removal	Surgical and medical procedures	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected17 at risk
Hypertension	Vascular disorders	26.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected17 at risk

ID	Term
D009103	Multiple Sclerosis

Ancestor Terms

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C533411	ocrelizumab