SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Ac... | NCT03713320

ID	Type	Description	Link
2018-000727-13	EudraCT Number

Label	Type	Description	Intervention Names
Cobomarsen	Experimental	Cobomarsen will be administered by intravenous 2-hour infusion at a dose of 282 mg on Days 1, 3, 5, 8, and weekly thereafter	Drug: Cobomarsen
Vorinostat	Active Comparator	Vorinostat will be administered orally at a dose of 400 mg (four 100-mg capsules) once daily with food, at approximately the same time each day.	Drug: Vorinostat

Name	Type	Description	Arm Group Labels	Other Names
Cobomarsen	Drug	At least weekly doses of cobomarsen (282 mg) throughout study treatment period	Cobomarsen

Measure	Description	Time Frame
Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)	ORR4 is the percentage of subjects with a complete response (CR) or partial response (PR) in the skin for 4 consecutive months confirmed by repeat assessments no less than 28 days (± 3 days) later. The modified Severity Weighted Assessment Tool (mSWAT) is used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores are calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores. Lower scores indicate a lower degree of skin disease severity. CR corresponds to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponds to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.	Date of first dose through the earlier of last study visit or interim analysis data cut-off date of 12-Oct-2020, up to 16 months

Measure	Description	Time Frame
Progression-free Survival (PFS)	Time from date of randomization until the date of earliest documented progression or death from any cause. The duration of PFS was censored at the date of the last mSWAT assessment if the subject was alive and had no documented progression. Disease progression in the skin is defined as ≥ 25% increase in mSWAT score from baseline or, in participants with complete or partial response, increase in mSWAT score of greater than the sum of the nadir plus 50% baseline score.

Measure	Description	Time Frame
Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose	Peak plasma concentration (Cmax) of cobomarsen after first dose	1, 1.92, 6, 24 and 48 hours post-dose after the first dose
Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5

Name	Affiliation	Role
Diana M. Escolar, MD, FAAN	miRagen Therapeutics, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
Mayo Clinic

PubMed Identifier	Type	Citation	Retractions
33085815	Derived	Ganguly K, Kishore U, Madan T. Interplay between C-type lectin receptors and microRNAs in cellular homeostasis and immune response. FEBS J. 2021 Jul;288(14):4210-4229. doi: 10.1111/febs.15603. Epub 2020 Nov 7.
32632956	Derived	Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.

ID	Title	Description
FG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
FG001

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	Feb 10, 2020

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

Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)

ORR4 is the percentage of subjects with a complete response (CR) or partial response (PR) in the skin for 4 consecutive months confirmed by repeat assessments no less than 28 days (± 3 days) later. The modified Severity Weighted Assessment Tool (mSWAT) is used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores are calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores. Lower scores indicate a lower degree of skin disease severity. CR corresponds to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponds to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.

Intent to treat population (includes all randomized subjects who received at least one dose of study treatment (cobomarsen or vorinostat) and had at least one post-baseline assessment. Assignment of subjects to treatment group is based on the planned treatment assignment.

Posted

Number

Percentage of participants

Date of first dose through the earlier of last study visit or interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Units	Counts
Participants	OG00019 OG00118

Title

Denominators

Categories

Title	Measurements
	OG00015.8 OG00116.7

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 OG001	Comparison of the treatment groups is based on a Cochran-Mantel-Haenzel test controlling for the number of tumors at screening (at least one tumor at screening versus no tumors at screening) and number of prognostic factors (0-1 versus 2 prognostic factors). Prognostic factors include age at diagnosis > 60 years and lactate dehydrogenase level > upper limit of normal at diagnosis. Number of subjects achieving ORR4 and exact binomial (Clopper-Pearson) confidence intervals are presented.	Cochran-Mantel-Haenszel		.9539														Superiority

Secondary

Progression-free Survival (PFS)

Time from date of randomization until the date of earliest documented progression or death from any cause. The duration of PFS was censored at the date of the last mSWAT assessment if the subject was alive and had no documented progression. Disease progression in the skin is defined as ≥ 25% increase in mSWAT score from baseline or, in participants with complete or partial response, increase in mSWAT score of greater than the sum of the nadir plus 50% baseline score.

Intent to treat population (includes all randomized subjects who received at least one dose of study treatment [cobomarsen or vorinostat] and had at least one post-baseline assessment). Assignment of subjects to treatment group is based on the planned treatment assignment.

Posted

Median

95% Confidence Interval

months

Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Complete Response Rate

Percentage of subjects with a complete response in the skin based on mSWAT

Posted

Number

Percentage of participants

Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Time to Progression

Time from date of randomization until the earliest date of confirmed progression

Posted

Mean

95% Confidence Interval

Months

Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Time to Maximal Effect in mSWAT

Time to greatest improvement in mSWAT score

Participants with improvement in mSWAT score

Posted

Mean

Standard Deviation

Months

Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Units	Counts
Participants

Secondary

Objective Response Rate in the Skin of at Least 28-days Duration (ORR1)

Percentage of participants achieving ≥ 50% improvement in mSWAT of at least 28-days duration

Posted

Number

percentage of participants

Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days

Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 28 days after first dose

Posted

Number

percentage of participants

28 days after first dose

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months

Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 4 months after first dose

Posted

Number

percentage of participants

4 months after first dose

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Secondary

Time to ≥ 50% Improvement in mSWAT

Time from date of randomization until ≥ 50% improvement in mSWAT score

Subjects who achieved an objective response in skin (≥ 50% improvement in mSWAT)

Posted

Mean

Standard Deviation

Months

Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Units	Counts

Secondary

Duration of Response in Skin

Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT)

Subjects who achieved an objective response in skin (≥ 50% improvement in mSWAT)

Posted

Median

95% Confidence Interval

Months

Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Units	Counts

Secondary

Pruritus Medication Utilization

Change from baseline in number of pruritus medications taken per subject

All subjects with any predose or postdose pruritus medications, including subjects with no predose medications and at least one postdose medication

Posted

Mean

Standard Deviation

Number of pruritus medications

Date of first dose through end of treatment or interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Other Pre-specified

Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose

Peak plasma concentration (Cmax) of cobomarsen after first dose

Population analyzed included those randomized to cobomarsen treatment.

Posted

Mean

Standard Deviation

µg/mL

1, 1.92, 6, 24 and 48 hours post-dose after the first dose

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion

Units	Counts
Participants	OG000

Other Pre-specified

Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5

Peak plasma concentration (Cmax) of cobomarsen after fourth dose (Week 5)

Population analyzed included those randomized to cobomarsen treatment.

Posted

Mean

Standard Deviation

µg/mL

1, 1.92 and 6 hours post-dose after the Week 5 dose

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion

Units	Counts
Participants	OG000

Other Pre-specified

Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5

Area under the curve (AUClast) for cobomarsen plasma concentration versus time curve after the fourth (Week 5) dose

Population analyzed included those randomized to cobomarsen treatment.

Posted

Mean

Standard Deviation

µg*hr/mL

1, 1.92 and 6 hours post-dose after the Week 5 dose

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants With Anti-drug Antibody Generation

Number of participants who develop antibodies to cobomarsen during treatment

The study was prematurely terminated for business reasons. No data were collected to evaluate this endpoint.

Posted

Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

ID	Title	Description
OG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobormarsen: 282 mg 2 hour IV infusion
OG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected18 at risk EG0020 events0 affected7 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0016 events5 affected18 at risk EG0020 events0 affected7 at risk
Anxiety	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected18 at risk EG0020 events0 affected7 at risk
Bacterial test positive	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Blood alkaline phosphatase increase	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Blood cholesterol increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0014 events1 affected18 at risk EG0020 events0 affected7 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Blood pressure decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Blood triglycerides increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Bradycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Chills	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0013 events2 affected18 at risk EG0020 events0 affected7 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0012 events2 affected18 at risk EG0020 events0 affected7 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Corona virus infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 events4 affected19 at risk EG0013 events2 affected18 at risk EG0020 events0 affected7 at risk
C-reactive protein increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Crystal urine present	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Deafness	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Deafness unilateral	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0014 events4 affected18 at risk EG0020 events0 affected7 at risk
Depressed mood	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected18 at risk EG0021 events1 affected7 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0009 events7 affected19 at risk EG00110 events8 affected18 at risk EG0021 events1 affected7 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Dry eye	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0005 events2 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected18 at risk EG0020 events0 affected7 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0013 events2 affected18 at risk EG0020 events0 affected7 at risk
Ear infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Eructation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Eye pain	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Eyelid oedema	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0003 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Face oedema	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG00012 events7 affected19 at risk EG00110 events6 affected18 at risk EG0022 events2 affected7 at risk
Feeling cold	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Feeling hot	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected18 at risk EG0021 events1 affected7 at risk
Flatulence	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Gastoenteritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0007 events5 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Hordeolum	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hot flush	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hyperaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG00010 events3 affected19 at risk EG00115 events5 affected18 at risk EG0023 events2 affected7 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Influenza like illness	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0014 events3 affected18 at risk EG0020 events0 affected7 at risk
Infusion site pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Keratitis	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Lethargy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected18 at risk EG0020 events0 affected7 at risk
Malaise	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0017 events6 affected18 at risk EG0020 events0 affected7 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0015 events3 affected18 at risk EG0020 events0 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 events8 affected19 at risk EG0017 events6 affected18 at risk EG0020 events0 affected7 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Overgrowth bacterial	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 events2 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Pain in extermity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Palmar erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Papule	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Paraesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected18 at risk EG0020 events0 affected7 at risk
Parosmia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Peripheral swelling	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0021 events1 affected7 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Proteinuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0013 events1 affected18 at risk EG0020 events0 affected7 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00020 events7 affected19 at risk EG0014 events4 affected18 at risk EG0020 events0 affected7 at risk
Pruritus allergic	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Pruritus generalized	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0003 events3 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Red blood cells urine positive	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Rhinitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Seasonal allergy	Immune system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Skin bacterial infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0007 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Skin infection	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00018 events5 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Skin plaque	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected18 at risk EG0021 events1 affected7 at risk
Skin weeping	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Superinfection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Superinfection bacterial	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected18 at risk EG0024 events1 affected7 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0014 events2 affected18 at risk EG0020 events0 affected7 at risk
Tonsillitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Tooth infection	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected18 at risk EG0020 events0 affected7 at risk
Toothache	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0013 events1 affected18 at risk EG0020 events0 affected7 at risk
Tumour inflammation	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Urine abnormality	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Urine albumin/creatinine ratio increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Vision blurred	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected18 at risk EG0020 events0 affected7 at risk
Weight increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
White blood cells urine positive	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected18 at risk EG0021 events1 affected7 at risk

ID	Term
D009182	Mycosis Fungoides
D016410	Lymphoma, T-Cell, Cutaneous
D008223	Lymphoma
D016399	Lymphoma, T-Cell
D008228	Lymphoma, Non-Hodgkin
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D009369	Neoplasms

ID	Term
D009370	Neoplasms by Histologic Type
D006425	Hemic and Lymphatic Diseases

ID	Term
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D006877	Hydroxamic Acids
D006898	Hydroxylamines
D006880	Hydroxy Acids
D002264	Carboxylic Acids

ID	Title	Description
BG000	Cobomarsen	Cobomarsen: At least weekly doses of cobomarsen (282 mg) throughout study treatment period
BG001	Vorinostat	Vorinostat: Daily doses of vorinostat throughout study treatment period
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cobomarsen (Randomized)	Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobomarsen: 282 mg 2 hour IV infusion	19	2	19	18	19
EG001	Vorinostat (Randomized)	Vorinostat (400 mg [4x100 mg capsules]) was administered orally once daily with food, at approximately the same time each day. Subjects with abnormal alanine aminotransferase/ aspartate aminotransferase (ALT/AST) (> upper limit of normal [ULN]) or bilirubin (> 1.0 × ULN) at screening were to start vorinostat dosing at 300 mg (three 100-mg capsules) once daily with food, at approximately the same time each day, per dosing guidelines. Vorinostat: 100 mg capsules	18	1	18	18	18
EG002	Cobomarsen (Crossover)	For subjects that were randomized to Vorinostat during the randomized period and were eligible to receive Cobomarsen during the crossover period: Cobomarsen was administered by intravenous 2-hour infusion at a dose of 282 mg of the active moiety (equivalent to 300 mg of the active pharmaceutical ingredient or sodium salt form) on Days 1, 3, 5, 8, and weekly thereafter. Cobomarsen: 282 mg 2 hour IV infusion	7	0	7	5	7

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk EG0020 events0 affected7 at risk
Skin infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk
Superinfection of Skin Lesions	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk EG0020 events0 affected7 at risk