Efficacy and Safety of Four Doses of Cenerimod Compared t... | NCT03742037

NCT03742037

ID	Type	Description	Link
2018-001808-11	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cenerimod 0.5 mg	Experimental	Participants will receive cenerimod 0.5 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 0.5 mg for a further 6 months and end study treatment at the Month 12 visit.	Drug: Cenerimod 0.5 mg
Cenerimod 1 mg	Experimental	Participants will receive cenerimod 1 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 1 mg for a further 6 months and end study treatment at the Month 12 visit.	Drug: Cenerimod 1 mg
Cenerimod 2 mg	Experimental	Participants will receive cenerimod 2 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 2 mg for a further 6 months and end study treatment at the Month 12 visit.	Drug: Cenerimod 2 mg
Cenerimod 2 mg (Ex-4mg)

Name	Type	Description	Arm Group Labels	Other Names
Cenerimod 0.5 mg	Drug	Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg	Cenerimod 0.5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score	The primary endpoint is the absolute change from baseline in the modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) score. The SLEDAI-2K is a cumulative index of lupus disease activity scored by the physician. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8, and measures disease activity within the last 10 days. 0 points indicates inactive disease, and 105 points is the maximum possible score. In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. Improvement in systemic lupus erythematosus disease activity is defined as a reduction in SLEDAI-2K score of greater than or equal to 4. A decreased score, i.e., a negative change, indicates an improvement in systemic lupus erythematosus disease activity from baseline to Month 6.	Baseline (Day 1) and Month 6

Secondary Outcomes

Measure	Description	Time Frame
Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline	A responder could only be assessed if the full information of all body systems was available. A participant was defined as a responder based on the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) was a composite, binary endpoint based on three variables: mSLEDAI-2K score had to have a reduction from baseline greater than or equal to 4, Physician Global Assessment (PGA) had to have an increase from baseline less than or equal to 0.3. The PGA is a 100 mm visual analog scale used by the physician to assess disease activity ranging for 0 to 3. The scale is anchored with values from 0 = "none" and 3 = "severe"), and BILAG-2004 (no new BILAG A organ domain score and at most one new BILAG B organ domain score) compared with baseline. If one of the SRI-4 mSLEDAI-2K, PGA and BILAG variables were not met the subject was scored a non-responder. Participants that did not fit at least one of the above criteria were assigned to the missing group.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed Informed Consent Form prior to any study-mandated procedure
Diagnosis of SLE made at least 6 months prior to Screening, by fulfilling at least 4 of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR) criteria
A mSLEDAI-2K score ≥ 6 of at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
Currently treated with stable doses of one or more of the following background medications:
- NSAIDs
- Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine)
- Mycophenolate mofetil (≤ 2 g/day)
- Mycophenolic acid (≤ 1440 mg/day)
- Azathioprine (≤ 2 mg/kg/day)
- Methotrexate (≤ 20 mg/week)
- Corticosteroids (≤ 40 mg/day prednisone or equivalent)
- Belimumab (≤10 mg/kg every 4 weeks intravenously, or 200 mg/week subcutaneously).
History or presence of positive autoantibodies measured by central laboratory defined as follows: (a) Positive antinuclear antibody (ANA) test measured by immunofluorescence assay (IFA) with titre ≥1:80; AND/OR (b) positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies with titre ≥30 IU/mL
Women of childbearing potential:
- Must have a negative serum pregnancy test at Screening
- Must agree to undertake monthly urine pregnancy tests during the study
- Must use highly effective methods of contraception from the screening visit until 6 months after taking the last dose of study treatment.

Exclusion Criteria:

Active lupus nephritis or a renal biopsy demonstrating immune complex mediated glomerulonephritis compatible with lupus nephritis.
CNS (Central Nervous System) lupus and severe forms of vasculitis requiring systemic immunosuppressive treatment
A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with rheumatoid arthritis, erosive arthritis, scleroderma or autoimmune hepatitis
History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders
Subjects who experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, vascular thrombosis, decompensated heart failure requiring hospitalization, or heart failure defined by the New York Heart Association Class III/IV within six months prior to Screening
An elevated QT corrected for HR (Heart Rate) on the basis of Fridericia's formula interval of > 470 ms (females) / > 450 ms (males)
History or presence of severe respiratory disease or pulmonary fibrosis
Active or latent tuberculosis
Ongoing bacterial, viral or fungal infection that is of clinical concern in the judgment of the investigator or history of any serious infection
Subjects who have congenital or acquired severe immunodeficiency or known HIV infection or positive HIV testing
Presence of macular edema or active uveitis
Type 1 or 2 diabetes that is poorly controlled according to investigator judgment, or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy
Significant hematology abnormality: Lymphocyte count < 800 /μL (0.8 × 10e9/L); hemoglobin < 9 g/dL; WBC (White Blood Cell) count < 2500/μL (2.5 × 10e9/L) or platelets < 75000/μL (75 × 10e9/L)
Estimated glomerular filtration rate < 60 mL/min/1.73 m2
Known allergy to S1P (sphingosine-1-phosphate) receptor modulators or any of the cenerimod formulation excipients

Name	Affiliation	Role
Clinical Trials	Viatris Innovation GmbH	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group		Anniston	Alabama	36207	United States
University of California San Diego

PubMed Identifier	Type	Citation	Retractions
39919901	Derived	Suffiotti M, Brazauskas P, Keller MP, Berkani O, Seifer G, Cornelisse P, Murphy MJ, Strasser DS. Pharmacodynamics of the S1P1 receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE. Ann Rheum Dis. 2025 Feb;84(2):284-293. doi: 10.1136/ard-2024-226547. Epub 2025 Jan 16.
39586304

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cenerimod 0.5 mg	Participants were randomized to receive cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6-months in Treatment Period 1. Participants completing Treatment Period 1 continued to receive cenerimod 0.5 mg once daily in addition to background SLE therapy during Treatment Period 2 for up to an additional 6 months. After end of treatment, participants entered a 6-month follow-up period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Protocol	Feb 4, 2022	May 22, 2023

Arm/Group Information

ID	Title	Description
BG000	Cenerimod 0.5 mg	Participants were randomized to receive cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
BG001	Cenerimod 1 mg	Participants were randomized to receive cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
BG002	Cenerimod 2 mg	Participants were randomized to receive cenerimod 2 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
BG003	Cenerimod 4 mg	Participants were randomized to receive cenerimod 4 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
BG004	Placebo	Participants were randomized to receive placebo once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
BG005	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
	BG00042.8± 12.41 BG00140.0± 12.77 BG00242.2± 12.06 BG003

Age, Customized

Number

years

Title

Denominators

Categories

Between 18 and 45 years

Title	Measurements
	BG00049 BG00154 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00079 BG00183 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00016 BG00117 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0005 BG0013 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Bulgaria

Title	Measurements
	BG0005 BG0012 BG002

Body Mass Index

Mean

Standard Deviation

kilograms/square meter

Title

Denominators

Categories

Title	Measurements
	BG00025.67± 5.67 BG00125.55± 5.95 BG002

modified SLEDAI at baseline

The SLEDAI-2K is a cumulative index of lupus disease activity. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8. 0 points indicates inactive disease, and 105 points is the maximum possible score (Gladman D et al. J Rheumatol 2002;29;288-291). In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. A score of 6 or greater is clinically relevant and associated with requiring lupus-directed therapy (Nuttall A et al. Best Pract Res Clin Rheumatol. 2013 Jun;27(3):309-18).

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0009.8± 2.69 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score

The primary endpoint is the absolute change from baseline in the modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) score. The SLEDAI-2K is a cumulative index of lupus disease activity scored by the physician. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8, and measures disease activity within the last 10 days. 0 points indicates inactive disease, and 105 points is the maximum possible score. In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. Improvement in systemic lupus erythematosus disease activity is defined as a reduction in SLEDAI-2K score of greater than or equal to 4. A decreased score, i.e., a negative change, indicates an improvement in systemic lupus erythematosus disease activity from baseline to Month 6.

Full Analysis Set (FAS).

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline (Day 1) and Month 6

ID	Title	Description
OG000	Cenerimod 0.5 mg	Participants received cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in treatment period 1.
OG001	Cenerimod 1 mg	Participants received cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in treatment period 1.
OG002	Cenerimod 2 mg	Participants received cenerimod 2 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
OG003	Cenerimod 4 mg	Participants received cenerimod 4 mg once daily in addition to background SLE therapy for up to 6-months in Treatment Period 1.
OG004	Placebo	Participants received placebo, matching cenerimod, once daily in addition to SLE therapy for up to 6 months in Treatment Period 1.

Units	Counts
Participants	OG00085 OG00185 OG00286 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-3.2(-3.98 to -2.49) OG001-3.41(-4.16 to -2.67) OG002-2.84(-3.58 to -2.09) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG004	The analysis was performed on the Full Analysis Set (FAS). The FAS included all participants who were randomized. Baseline was defined as the last measurement before randomization.	Mixed Models Analysis		0.4749		LS mean difference to placebo	-0.39	Standard Error of the Mean	0.54	2-Sided	95	-1.45	0.68					Superiority
OG001

Secondary

Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline

A responder could only be assessed if the full information of all body systems was available. A participant was defined as a responder based on the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) was a composite, binary endpoint based on three variables:

mSLEDAI-2K score had to have a reduction from baseline greater than or equal to 4,
Physician Global Assessment (PGA) had to have an increase from baseline less than or equal to 0.3. The PGA is a 100 mm visual analog scale used by the physician to assess disease activity ranging for 0 to 3. The scale is anchored with values from 0 = "none" and 3 = "severe"), and
BILAG-2004 (no new BILAG A organ domain score and at most one new BILAG B organ domain score) compared with baseline.

If one of the SRI-4 mSLEDAI-2K, PGA and BILAG variables were not met the subject was scored a non-responder. Participants that did not fit at least one of the above criteria were assigned to the missing group.

Full Analysis Set (FAS)

Posted

Number

participants

Baseline (Day 1) and Month 6

ID	Title	Description
OG000	Cenerimod 0.5 mg	Participants received cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
OG001	Cenerimod 1 mg	Participants received cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.

Secondary

British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6

The British Isles Lupus Assessment Group-2004 (BILAG) is a comprehensive tool used by the physician to assess disease activity and is sensitive to small changes over time.

Response (no worsening) at Month 6 on BILAG-2004 disease activity index was defined as no new BILAG A organ domain score and no more than one new BILAG B organ domain score compared with baseline.

No analysis is reported because the model did not meet the convergence criteria.

Full analysis set (FAS).

Posted

Number

percentage of participants

Baseline (Day 1) and Month 6

ID	Title	Description
OG000	Cenerimod 0.5 mg	Participants received cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
OG001	Cenerimod 1 mg	Participants received cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.
OG002	Cenerimod 2 mg	Participants received cenerimod 2 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1.

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	Cenerimod 0.5 mg (Treatment Period 1 & 2)	Participants received cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. Participants completing Treatment Period 1 continued with cenerimod 0.5 mg once daily in addition to background SLE therapy during treatment period 2 for up to an additional 6 months. After end of treatment, participants entered a 6-month follow-up period.	0	84	4	84	37	84
EG001	Cenerimod 1 mg (Treatment Period 1 & 2)	Participants received cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. Participants completing Treatment Period 1 continued to receive cenerimod 1 mg once daily in addition to background SLE therapy during Treatment Period 2 for up to an additional 6 months. After end of treatment, participants entered a 6-month follow-up period.	2	85	12	85	54	85
EG002	Cenerimod 2 mg (Treatment Period 1 & 2)	Participants received cenerimod 2 mg once daily in addition to background SLE therapy for up to 6 months in treatment period 1. Participants completing Treatment Period 1 continued to receive cenerimod 2 mg once daily in addition to background SLE therapy during Treatment Period 2 for up to an additional 6 months. After end of treatment, participants entered a 6-month follow-up period.	0	87	4	87	53	87
EG003	Cenerimod 4 mg (Treatment Period 1) & Cenerimod 2 mg (Ex-4 mg; Treatment Period 2)	Half the participants completing treatment with cenerimod 4 mg in Treatment Period 1 were re-randomized to cenerimod 2 mg once daily in addition to background SLE therapy during Treatment Period 2. Participants received cenerimod 2 mg for up to 6 months. After end of treatment, participants entered a 6-month follow-up period.	0	35	1	35	23	35
EG004	Cenerimod 4 mg (Treatment Period 1) & Placebo (Ex-4 mg; Treatment Period 2)	Half the participants completing treatment with cenerimod 4 mg in Treatment Period 1 were re-randomized to placebo once daily in addition to background SLE therapy during Treatment Period 2. Participants received placebo for up to 6 months. After end of treatment, participants entered a 6-month follow-up period.	0	35	0	35	20	35
EG005	Cenerimod 4 mg (Treatment Period 1) & Not Re-randomized (Ex-4 mg; Treatment Period 2)	Participants were not re-randomized and did not receive treatment in Treatment Period 2. (These participants previously received cenerimod 4 mg once daily in addition to background SLE therapy for 6 months in treatment period 1). After end of treatment, participants entered a 6-month follow-up period.	0	14	2	14	13	14
EG006	Placebo (Treatment Period 1 & 2)	Participants received placebo once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. Participants completing Treatment Period 1 continued with placebo once daily in addition to background SLE therapy during Treatment Period 2 for up to an additional 6 months. After end of treatment, participants entered a 6-month follow-up period.	0	86	6	86	39	86

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0012 events2 affected85 at risk EG0020 events0 affected87 at risk EG0030 events0 affected35 at risk EG0040 events0 affected35 at risk EG0050 events0 affected14 at risk EG0060 events0 affected86 at risk
Angina pectoris	Cardiac disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Duodenal perforation	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Hepatic mass	Hepatobiliary disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0012 events2 affected85 at risk EG0020 events0 affected87 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0012 events2 affected85 at risk EG0020 events0 affected87 at risk EG003
Cellulitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Cerebral toxoplasmosis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Pneumonia	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0012 events2 affected85 at risk EG0020 events0 affected87 at risk EG003
Benign ovarian tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Cutaneous vasculitis	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Systemic lupus erythematosus rash	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Hypertensive emergency	Vascular disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphopenia	Blood and lymphatic system disorders	MedDRA 25.0	Non-systematic Assessment	EG0004 events4 affected84 at risk EG00112 events10 affected85 at risk EG00218 events12 affected87 at risk EG00312 events7 affected35 at risk EG0044 events4 affected35 at risk EG0057 events5 affected14 at risk EG0061 events1 affected86 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected84 at risk EG0017 events4 affected85 at risk EG0021 events1 affected87 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0023 events2 affected87 at risk EG003
Cataract subcapsular	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Dry eye	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected84 at risk EG0012 events2 affected85 at risk EG0029 events9 affected87 at risk EG003
Eye irritation	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Eye pain	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Vision blurred	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0021 events1 affected87 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0016 events6 affected85 at risk EG0020 events0 affected87 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0012 events2 affected85 at risk EG0020 events0 affected87 at risk EG003
Acid peptic disease	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0006 events4 affected84 at risk EG0016 events4 affected85 at risk EG0024 events3 affected87 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0014 events2 affected85 at risk EG0021 events1 affected87 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected84 at risk EG0013 events1 affected85 at risk EG0021 events1 affected87 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0011 events1 affected85 at risk EG0021 events1 affected87 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0013 events3 affected85 at risk EG0022 events2 affected87 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0008 events8 affected84 at risk EG0019 events8 affected85 at risk EG00210 events10 affected87 at risk EG003
Cellulitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Eyelid infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0005 events5 affected84 at risk EG0010 events0 affected85 at risk EG0026 events6 affected87 at risk EG003
Ophthalmic herpes simplex	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Oral herpes	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected84 at risk EG0015 events2 affected85 at risk EG0025 events5 affected87 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0008 events7 affected84 at risk EG0015 events4 affected85 at risk EG0025 events5 affected87 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected84 at risk EG0012 events2 affected85 at risk EG0022 events2 affected87 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Bone contusion	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0017 events5 affected85 at risk EG0023 events3 affected87 at risk EG003
Forced expiratory volume decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0021 events1 affected87 at risk EG003
Liver function test abnormal	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0025 events5 affected87 at risk EG003
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0012 events2 affected85 at risk EG0023 events3 affected87 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0012 events2 affected85 at risk EG0026 events4 affected87 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0014 events3 affected85 at risk EG0021 events1 affected87 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0021 events1 affected87 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0012 events2 affected85 at risk EG0021 events1 affected87 at risk EG003
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0015 events5 affected85 at risk EG0021 events1 affected87 at risk EG003
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Headache	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG00012 events11 affected84 at risk EG00113 events12 affected85 at risk EG0029 events8 affected87 at risk EG003
Somnolence	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk EG0020 events0 affected87 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk EG0021 events1 affected87 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Brachioradial pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Macule	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected84 at risk EG0010 events0 affected85 at risk EG0020 events0 affected87 at risk EG003
Hypertension	Vascular disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected84 at risk EG0018 events8 affected85 at risk EG0023 events3 affected87 at risk EG003

ID	Term
D008180	Lupus Erythematosus, Systemic
D003240	Connective Tissue Diseases

ID	Term
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases