Study of Efficacy and Safety of Canakinumab in Patients W... | NCT02059291

Status Module

Oversight Module

Description 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
crFMF: 150 mg	Experimental	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.	Drug: Canakinumab
crCMF: placebo	Placebo Comparator	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg.	Drug: Placebo
HIDS/MKD: 150 mg	Experimental	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Canakinumab	Drug	Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.	HIDS/MKD: 150 mg TRAPS: 150 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)	Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) <2 and C-reactive protein (CRP) within normal range (<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.	16 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2	The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Los Angeles	California	90027	United States
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37668289	Derived	Gattorno M, Obici L, Penades IC, Kallinich T, Benseler S, Dekker E, Levy J, De Benedetti F, Lachmann H. Long-Term Efficacy and Safety of Canakinumab in Patients With Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Results From a Phase III Trial. Arthritis Rheumatol. 2024 Feb;76(2):304-312. doi: 10.1002/art.42695. Epub 2023 Dec 8.
34554243

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.

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	Oct 22, 2014	Dec 7, 2017

Arm/Group Information

ID	Title	Description
BG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
BG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg
BG002	Epoch 2: HIDS/MKD: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
BG003	Epoch 2: HIDS/MKD: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.
BG004	Epoch 2: TRAPS: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration
BG005	Epoch 2: TRAPS: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between Day 8 and 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.
BG006	Epoch 2: Non-randomized Open Label Treatment - crFMF	Canakinumab-naïve Japanese patients with non-exon 10 mutations received open-label canakinumab 150 mg (or 2 mg/kg for patients weighing ≤ 40 kg) q4w
BG007	Epoch 2: Non-randomized Open Label HIDS/MKD	Participants in the 28 days to less than 2 years old cohort who received open-label canakinumab 150 mg (or 2mg/kg for patients weighing ≤ 40 kg) q4w.
BG008	Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS	Open-label treatment in Epoch 3 was initiated for TRAPS patients who rolled over from CACZ885D2203 or CACZ885D2207M.
BG009	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

Median

Full Range

Years

Title

Denominators

Categories

crFMF cohort - randomized

Title	Measurements
	BG00018.0± 15.02(2 to 60) BG00118.0± 13.38(4 to 69) BG002NA± NA(NA to NA)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014 BG00115 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

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 Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)

Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) <2 and C-reactive protein (CRP) within normal range (<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.

The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.

Posted

Number

Percentage of participants

16 weeks

ID	Title	Description
OG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg
OG002	Epoch 2: HIDS/MKD: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG003	Epoch 2: HIDS/MKD: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.
OG004	Epoch 2: TRAPS: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration
OG005	Epoch 2: TRAPS: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between Day 8 and 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.

Units	Counts
Participants	OG00031 OG00132 OG00237 OG003

Title

Denominators

Categories

Title	Measurements
	OG00061.29 OG0016.25 OG00235.14 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 OG001		Fisher's exact test		<0.0001														Superiority
OG002 OG003		Fisher's exact test		0.0020

Secondary

Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2

The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.

The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.

Posted

Number

Percentage of participants

16 weeks

ID	Title	Description
OG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg

Secondary

Percentage of Participants With the Serologic Remission

Serologic remission was defined as C-reactive protein <= 10 mg/L.

The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.

Posted

Number

Percentage of participants

16 weeks

ID	Title	Description
OG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg

Secondary

Percentage of Participants With Normalized Serum Amyloid A (SAA) Level

Normalized SAA was defined as SAA <= 10 mg/L.

The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.

Posted

Number

Percentage of participants

16 weeks

ID	Title	Description
OG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg

Secondary

Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)

A responder was defined as a participant who had no flare between week 16 and week 40.

The re-randomized set was analyzed.

Posted

Number

Percentage of participants

40 weeks

ID	Title	Description
OG000	Epoch 2: crFMF: 150 mg	During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing <= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
OG001	Epoch 2: crCMF: Placebo	During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing <= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Non-randomized Open Label crFMF, HIDS/MKD Patients	Canakinumab-naïve Japanese patients with non-exon 10 mutations with cr-FMF who received open-label canakinumab 150 mg (or 2 mg/kg for patients weighing ≤ 40 kg) q4w; and patients in the 28 days to less than 2 years old cohort with HIDS/MKD who received open-label canakinumab 150 mg (or 2mg/kg for patients weighing ≤ 40 kg) q4w	4	3	4	4	4
EG001	Non-randomized Open Label TRAPS Patients	Open-label treatment in Epoch 3 was initiated for TRAPS patients who rolled over from CACZ885D2203 or CACZ885D2207M	18	1	18	18	18
EG002	Randomized ACZ and Placebo TRAPS Patients - Placebo Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3.	46	1	46	14	46
EG003	Randomized ACZ and Placebo TRAPS Pts - No Medication Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3 .	46	0	46	1	46
EG004	Randomized ACZ and Placebo TRAPS Patients - ACZ Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	46	8	46	43	46
EG005	Randomized ACZ and Placebo HIDS/MKD Pts - Placebo Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	72	6	72	25	72
EG006	Randomized ACZ and Placebo HIDS/MKD Pts - No Medication Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	72	1	72	1	72
EG007	Randomized ACZ and Placebo HIDS/MKD Patients - ACZ Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	72	16	72	68	72
EG008	Randomized ACZ and Placebo crFMF Patients - Placebo Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	63	5	63	29	63
EG009	Randomized ACZ and Placebo crFMF Pts - No Medication Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	63	0	63	2	63
EG010	Randomized ACZ and Placebo crFMF Patients - ACZ Events	Patients who received ACZ885 and/or placebo during epoch 2 and/or epoch 3	63	16	63	54	63
EG011	Any ACZ TRAPS Patients - Placebo Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	0	61	4	61
EG012	Any ACZ TRAPS Patients - no Medication Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	0	61	1	61
EG013	Any ACZ TRAPS Patients - ACZ Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	9	61	61	61
EG014	Any ACZ HIDS/MKD Patients - Placebo Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	71	3	71	7	71
EG015	Any ACZ HIDS/MKD Patients - No Medication Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	71	1	71	1	71
EG016	Any ACZ HIDS/MKD Patients - ACZ Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	71	18	71	70	71
EG017	Any ACZ crFMF Patients - Placebo Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	3	61	10	61
EG018	Any ACZ crFMF Patients - No Medication Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	0	61	2	61
EG019	Any ACZ crFMF Patients - ACZ Events	Patients who received ACZ885 during epoch 2 and/or epoch 3	61	17	61	56	61

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG0030 affected46 at risk EG0040 affected46 at risk EG0050 affected72 at risk EG0060 affected72 at risk EG0071 affected72 at risk EG0080 affected63 at risk EG0090 affected63 at risk EG0100 affected63 at risk EG0110 affected61 at risk EG0120 affected61 at risk EG0130 affected61 at risk EG0140 affected71 at risk EG0150 affected71 at risk EG0161 affected71 at risk EG0170 affected61 at risk EG0180 affected61 at risk EG0190 affected61 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pericarditis	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Familial mediterranean fever	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hyper IgD syndrome	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Tumour necrosis factor receptor-associated periodic syndrome	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Thyroiditis	Endocrine disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Ileal ulcer	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hyperpyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Polyserositis	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Granulomatous liver disease	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Acute sinusitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Anal abscess	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Appendicitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Atypical pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Bronchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Cellulitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Diarrhoea infectious	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Gastroenteritis rotavirus	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Herpes virus infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Infectious colitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Influenza	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Laryngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Orchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pelvic abscess	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Peritonitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pharyngotonsillitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Septic shock	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Tonsillitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Vulval abscess	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Scar	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Seizure	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Depression	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Intentional self-injury	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Schizophrenia	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Laryngeal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Vocal cord polyp	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Granulomatous rosacea	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pyoderma gangrenosum	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG0030 affected46 at risk EG0040 affected46 at risk EG0051 affected72 at risk EG0060 affected72 at risk EG0074 affected72 at risk EG0081 affected63 at risk EG0090 affected63 at risk EG0103 affected63 at risk EG0110 affected61 at risk EG0120 affected61 at risk EG0131 affected61 at risk EG0140 affected71 at risk EG0150 affected71 at risk EG0164 affected71 at risk EG0170 affected61 at risk EG0180 affected61 at risk EG0193 affected61 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Familial mediterranean fever	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hyper IgD syndrome	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Tumour necrosis factor receptor-associated periodic syndrome	Congenital, familial and genetic disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0022 affected46 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Eye allergy	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Eye pain	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Scleritis	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected18 at risk EG0021 affected46 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected18 at risk EG0022 affected46 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected4 at risk EG0014 affected18 at risk EG0021 affected46 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected18 at risk EG0020 affected46 at risk EG003
Gastric dilatation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Proctitis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Teething	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Asthenia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Fatigue	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Influenza like illness	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Injection site reaction	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Malaise	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0015 affected18 at risk EG0021 affected46 at risk EG003
Bronchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Cystitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Ear infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Influenza	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected18 at risk EG0021 affected46 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Oral herpes	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Otitis media	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Otitis media acute	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Paronychia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pharyngotonsillitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pilonidal cyst	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Rhinitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected18 at risk EG0020 affected46 at risk EG003
Sialoadenitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Sinusitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Tonsillitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Tonsillitis bacterial	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Tracheitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected18 at risk EG0020 affected46 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected18 at risk EG0022 affected46 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Viral infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Viral tonsillitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0015 affected18 at risk EG0021 affected46 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
C-reactive protein increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Eosinophil count increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Glomerular filtration rate decreased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Neutrophil count increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Serum amyloid A protein increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0013 affected18 at risk EG0022 affected46 at risk EG003
White blood cell count increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0015 affected18 at risk EG0022 affected46 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected18 at risk EG0020 affected46 at risk EG003
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected18 at risk EG0022 affected46 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected18 at risk EG0020 affected46 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0013 affected18 at risk EG0021 affected46 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Tendon pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Tenosynovitis stenosans	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Pyogenic granuloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Dizziness	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Headache	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected18 at risk EG0023 affected46 at risk EG003
Somnolence	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Breast mass	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Polycystic ovaries	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected18 at risk EG0020 affected46 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0021 affected46 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Keloid scar	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Pyoderma gangrenosum	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0020 affected46 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected18 at risk EG0021 affected46 at risk EG003
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected18 at risk EG0020 affected46 at risk EG003
Hypotension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected18 at risk EG0020 affected46 at risk EG003