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Clinical Trial Results:
A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PARALLEL-ARM, PLACEBO-CONTROLLED MAINTENANCE STUDY OF MIRIKIZUMAB IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS (LUCENT 2)

Summary
EudraCT number	2017-003238-96
Trial protocol	DE GB NL LV CZ LT ES BE HU AT SK DK HR IT RO
Global end of trial date

Results information
Results version number	v1(current)
This version publication date	15 Dec 2022
First version publication date	15 Dec 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

I6T-MC-AMBG

ISRCTN number

-

US NCT number

NCT03524092

WHO universal trial number (UTN)

-

Other trial identifiers

Trial Number: 16823

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Interim

Date of interim/final analysis

03 Nov 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 Nov 2021

Global end of trial reached?

No

Main objective of the trial

The purpose of this study is to evaluate the efficacy and safety of mirikizumab as maintenance therapy in participants who completed as clinical responders in the prior 12-week induction study LUCENT-1 (NCT03518086).

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

19 Oct 2018

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 11

Country: Number of subjects enrolled

Australia: 12

Country: Number of subjects enrolled

Austria: 8

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Canada: 31

Country: Number of subjects enrolled

China: 15

Country: Number of subjects enrolled

Czechia: 52

Country: Number of subjects enrolled

Denmark: 7

Country: Number of subjects enrolled

France: 57

Country: Number of subjects enrolled

Germany: 37

Country: Number of subjects enrolled

Hungary: 23

Country: Number of subjects enrolled

India: 72

Country: Number of subjects enrolled

Ireland: 1

Country: Number of subjects enrolled

Israel: 15

Country: Number of subjects enrolled

Italy: 36

Country: Number of subjects enrolled

Japan: 123

Country: Number of subjects enrolled

Latvia: 29

Country: Number of subjects enrolled

Lithuania: 22

Country: Number of subjects enrolled

Malaysia: 6

Country: Number of subjects enrolled

Mexico: 10

Country: Number of subjects enrolled

Netherlands: 10

Country: Number of subjects enrolled

Poland: 122

Country: Number of subjects enrolled

Romania: 14

Country: Number of subjects enrolled

Russian Federation: 100

Country: Number of subjects enrolled

Serbia: 21

Country: Number of subjects enrolled

Slovakia: 21

Country: Number of subjects enrolled

Korea, Republic of: 25

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

Switzerland: 10

Country: Number of subjects enrolled

Taiwan: 3

Country: Number of subjects enrolled

Turkey: 8

Country: Number of subjects enrolled

Ukraine: 93

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

United States: 140

Worldwide total number of subjects

1177

EEA total number of subjects

468

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

1083

From 65 to 84 years

94

85 years and over

0

Subject disposition

Top of page

Recruitment details

-

Screening details

This study was designed to evaluate the safety and efficacy of mirikizumab (miri) in achieving remission at Week (Wk) 40 in participants who completed the 12-week induction study I6T-MC-AMAN (NCT03518086) as clinical responders to mirikizumab. Results for maximum extended enrollment (ME2) participants will be posted after the study completion.

Period 1 title

Blinded Maintenance Period (Wk 0-40)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)

Arm description

Participants who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

PBO SC every 4 weeks (Q4W).

Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Arm description

Participants who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Arm type

Experimental

Investigational medicinal product name

Mirikizumab

Investigational medicinal product code

Other name

LY3074828

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

200 mg mirikizumab SC Q4W.

Maintenance Period: PBO IR - PBO SC

Arm description

Participants who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Arm type

PBO IR

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

PBO SC every 4 weeks (Q4W).

Number of subjects in period 1 ^[1]	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC	Maintenance Period: PBO IR - PBO SC
Started	192	389	135
Received at Least One Dose of Study Drug	192	389	135
Completed	119	347	90
Not completed	73	42	45
Consent withdrawn by subject	7	8	6
Physician decision	-	1	-
Adverse event, non-fatal	16	6	1
Pregnancy	-	-	1
Loss of Response Rescue Period	42	19	29
Lost to follow-up	-	1	-
Lack of efficacy	8	6	7
Protocol deviation	-	1	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Data is reported separately for Blinded Maintenance Period as Induction Responder (IR) and open label extended Induction period as Induction Nonresponders.

Period 2 title

Open Label Extended Induction (Wk 0-12)

Is this the baseline period?

No

Allocation method

Not applicable

Blinding used

Not blinded

Extended Induction: Induction Nonresponders - 300mg Miri IV

Arm description

Participants who were nonresponders to blinded mirikizumab or placebo in induction study (LUCENT-1), received additional 3 doses of open label 300 mg mirikizumab IV Q4W during extended induction period from Week 0 of LUCENT-2 until Week 12.

Arm type

Induction Nonresponders

Investigational medicinal product name

Mirikizumab

Investigational medicinal product code

Other name

LY3074828

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

300 mg mirikizumab IV Q4W for 3 doses.

Number of subjects in period 2 ^[2]	Extended Induction: Induction Nonresponders - 300mg Miri IV
Started	461
Completed	271
Not completed	190
Physician decision	1
Consent withdrawn by subject	6
Lack of capacity due to lack of staff	1
Adverse event, non-fatal	11
Covid-19 related study disruption	4
Lack of efficacy	162
Protocol deviation	5

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Included only participants who entered open label extended induction period.

Period 3 title

Open Label Maintenance Period (Wk 12-40)

Is this the baseline period?

No

Allocation method

Not applicable

Blinding used

Not blinded

Open Label Maintenance Period (Wk 12-40)

Arm description

Participants who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40 or until early termination (rescue was not available for these participants).

Arm type

Open Label Maintenance Period

Investigational medicinal product name

Mirikizumab

Investigational medicinal product code

Other name

LY3074828

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

200 mg mirikizumab SC Q4W.

Number of subjects in period 3	Open Label Maintenance Period (Wk 12-40)
Started	271
Completed	256
Not completed	15
Adverse event, non-fatal	4
Covid-19 related study disruption	1
Lack of efficacy	9
Protocol deviation	1

Period 4 title

Loss of Response Rescue Period

Is this the baseline period?

No

Allocation method

Not applicable

Blinding used

Not blinded

Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV

Arm description

Participants who received blinded PBO SC or blinded 200 mg mirikizumab SC Q4W during maintenance period and experienced a loss of response at or after Week 12, received rescue therapy with open label 300 mg mirikizumab intravenous (IV) Q4W for 3 doses.

Arm type

LOR Rescue Period

Investigational medicinal product name

Mirikizumab

Investigational medicinal product code

Other name

LY3074828

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

300 mg mirikizumab IV Q4W.

Number of subjects in period 4 ^[3]	Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV
Started	90
Completed	81
Not completed	9
Consent withdrawn by subject	1
Adverse event, non-fatal	2
Pregnancy	1
Lack of efficacy	5

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Included only participants who experienced loss of response and were eligible for loss of response rescue induction.

Baseline characteristics

Top of page

Reporting group title

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)

Reporting group description

Participants who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.

Reporting group title

Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Reporting group description

Participants who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Reporting group title

Maintenance Period: PBO IR - PBO SC

Reporting group description

Participants who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Reporting group values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC	Maintenance Period: PBO IR - PBO SC	Total
Number of subjects	192	389	135	716
Age categorical
Units: Subjects
Age continuous
All randomized participants who are responders to Miri and PBO in induction study (LUCENT-1).
Units: years
arithmetic mean (standard deviation)	41.20 ± 12.88	43.30 ± 14.13	40.80 ± 13.40	-
Gender categorical
All randomized participants who are responders to Miri and PBO in induction study (LUCENT-1).
Units: Subjects
Female	78	160	61	299
Male	114	229	74	417
Ethnicity
All randomized participants who are responders to Miri and PBO in induction study (LUCENT-1). Ethnicity data collected only for United States (US) participants.
Units: Subjects
Hispanic or Latino	2	12	2	16
Not Hispanic or Latino	18	33	8	59
Unknown or Not Reported	172	344	125	641
Race
All randomized participants who are responders to Miri and PBO in induction study (LUCENT-1).
Units: Subjects
American Indian or Alaska Native	1	3	2	6
Asian	51	93	28	172
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	6	0	6
White	138	285	103	526
More than one race	0	0	2	2
Unknown or Not Reported	2	2	0	4
Region of Enrollment
All randomized participants who are responders to Miri and PBO in induction study (LUCENT-1).
Units: Subjects
Argentina	1	5	0	6
Australia	0	3	0	3
Austria	2	2	0	4
Belgium	1	2	2	5
Canada	3	5	2	10
China	3	4	1	8
Czechia	7	19	11	37
Denmark	3	3	0	6
France	10	18	6	34
Germany	5	13	3	21
Hungary	1	8	2	11
India	18	25	16	59
Ireland	0	1	0	1
Israel	3	6	1	10
Italy	3	12	4	19
Japan	25	47	8	80
Latvia	8	10	3	21
Lithuania	6	4	5	15
Malaysia	0	3	0	3
Mexico	1	3	2	6
Netherlands	1	6	0	7
Poland	15	32	13	60
Romania	4	2	0	6
Russia	19	36	16	71
Serbia	1	9	4	14
Slovakia	6	7	1	14
South Korea	3	8	1	12
Spain	1	6	4	11
Switzerland	0	4	0	4
Taiwan	1	1	0	2
Turkey	0	5	2	7
Ukraine	18	31	16	65
United Kingdom	2	4	2	8
United States	21	45	10	76

End points

Top of page

Reporting group title

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)

Reporting group description

Participants who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.

Reporting group title

Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Reporting group description

Participants who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Reporting group title

Maintenance Period: PBO IR - PBO SC

Reporting group description

Participants who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Reporting group title

Extended Induction: Induction Nonresponders - 300mg Miri IV

Reporting group description

Participants who were nonresponders to blinded mirikizumab or placebo in induction study (LUCENT-1), received additional 3 doses of open label 300 mg mirikizumab IV Q4W during extended induction period from Week 0 of LUCENT-2 until Week 12.

Reporting group title

Open Label Maintenance Period (Wk 12-40)

Reporting group description

Participants who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40 or until early termination (rescue was not available for these participants).

Reporting group title

Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV

Reporting group description

Participants who received blinded PBO SC or blinded 200 mg mirikizumab SC Q4W during maintenance period and experienced a loss of response at or after Week 12, received rescue therapy with open label 300 mg mirikizumab intravenous (IV) Q4W for 3 doses.

Subject analysis set title

200 Milligram (mg) Miri SC

Subject analysis set type

Per protocol

Subject analysis set description

Participants who received 200 mg mirikizumab SC every Q4W.

Primary: Percentage of Participants in Clinical Remission at Week 40

Top of page

End point title

Percentage of Participants in Clinical Remission at Week 40 ^[1]

End point description

Clinical remission at week 40 is defined as achieving a 9-point modified Mayo score for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability). Stool Frequency Subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); Rectal Bleeding Subscore, based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); Endoscopy Subscore, based on central reading of colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). Analysis population description (APD): Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Primary

End point timeframe

Week 40

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	25.1 (18.8 to 31.5)	49.9 (44.7 to 55.0)

Percentage of Participants in Clinical Remission

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

23.2

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

31.2

Secondary: Percentage of Participants in Endoscopic Remission at Week 40

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End point title

Percentage of Participants in Endoscopic Remission at Week 40 ^[2]

End point description

Endoscopic remission at week 40 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) at Week 40. Endoscopy subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Week 40

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	29.1 (22.4 to 35.7)	58.6 (53.6 to 63.7)

Percentage of Participants in Endoscopic Remission

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

28.5

Confidence interval

level

95%

sides

2-sided

lower limit

20.2

upper limit

36.8

Secondary: Percentage of Participants with Histologic Remission at Week 40

Top of page

End point title

Percentage of Participants with Histologic Remission at Week 40 ^[3]

End point description

Histologic remission was assessed using the Geboes histologic scoring system developed for assessment of histologic disease activity in ulcerative colitis. Remission was defined as Geboes histological subscore of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils in epithelium), and 4 (crypt destruction), and 5 (erosion or ulceration). APD: Modified Intention-to-treat population (mITT): All randomized participants (pts) who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Week 40

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	24.6 (18.3 to 30.9)	48.5 (43.4 to 53.6)

Percentage of Pts with Histologic Remission

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

22.5

Confidence interval

level

95%

sides

2-sided

lower limit

14.5

upper limit

30.5

Secondary: Percentage of Participants in Symptomatic Remission at Week 40

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End point title

Percentage of Participants in Symptomatic Remission at Week 40 ^[4]

End point description

Symptomatic remission at week 40 is defined as a Mayo score for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline. Stool frequency subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal). Rectal bleeding subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed). APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Week 40

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	39.7 (32.5 to 46.8)	71.0 (66.3 to 75.6)

Percentage of Pts in Symptomatic Remission

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

30.2

Confidence interval

level

95%

sides

2-sided

lower limit

21.9

upper limit

38.6

Secondary: Percentage of Participants in Endoscopic Response at Week 40

Top of page

End point title

Percentage of Participants in Endoscopic Response at Week 40 ^[5]

End point description

Endoscopic response at week 40 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore. APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Week 40

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	40.8 (33.6 to 48.0)	72.6 (68.0 to 77.2)

Percentage of Participants in Endoscopic Response

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

31

Confidence interval

level

95%

sides

2-sided

lower limit

22.4

upper limit

39.6

Secondary: Percentage of Participants in Clinical Response at Week 40

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End point title

Percentage of Participants in Clinical Response at Week 40 ^[6]

End point description

Clinical response at week 40 is defined as a decrease in the 9-point modified Mayo score (MMS) [rectal bleeding, stool frequency and the endoscopic findings] inclusive of >= 2 points and >=30% from baseline with either a decrease of rectal bleeding subscore of >=1 or rectal bleeding subscore of 0 or 1.The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three subscores: Stool frequency subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); Rectal bleeding subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration). APD: mITT: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline.

End point type

Secondary

End point timeframe

Week 40 Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (confidence interval 95%)	49.2 (41.8 to 56.5)	80.3 (76.2 to 84.4)

Percentage of Participants in Clinical Response

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

30.6

Confidence interval

level

95%

sides

2-sided

lower limit

22.3

upper limit

38.9

Secondary: Change from Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

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End point title

Change from Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score ^[7]

End point description

The IBDQ is a 32-item participant-completed questionnaire that measures 4 aspects of subjects' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function. Responses are graded on a 7-point. Likert scale in which 7 denotes "not a problem at all" and 1 denotes "a very severe problem." Scores range from 32 to 224; a higher score indicates a better quality of life. Least square (LS) Mean was calculated using analysis of covariance (ANCOVA) model for post-baseline measures: The ANCOVA model includes: treatment, baseline value, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), clinical remission status (yes/no) at AMAN Week 12, and region (North America/Europe/Other). Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Induction Baseline, Week 40 APD: mITT: All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline IBDQ measurement.

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: score on a scale
least squares mean (standard error)	24.51 ± 2.767	49.75 ± 2.102

Change from Baseline to Week 40 in IBDQ

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

ANCOVA

Parameter type

LS Mean difference (Final Values)

Point estimate

25.24

Confidence interval

level

95%

sides

2-sided

lower limit

19.16

upper limit

31.32

Variability estimate

Standard error of the mean

Dispersion value

3.094

Notes
[8] - ANCOVA with modified baseline observation carried forward (mBOCF).

Secondary: Change from Baseline to Week 40 in Fecal Calprotectin

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End point title

Change from Baseline to Week 40 in Fecal Calprotectin ^[9]

End point description

Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Least square (LS) Mean was calculated using ANCOVA model for post-baseline measures: The ANCOVA model includes treatment, baseline value, prior biologic or tofacitinib failure (yes/no), corticosteroid use (yes/no) at AMAN baseline, region (North America/Europe/Other), Clinical Remission status (yes/no) at AMAN Week 12. APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline fecal calprotectin measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Induction Baseline, Week 40

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: milligram per kilogram (mg/kg)
least squares mean (standard error)	-1155.82 ± 221.394	-1995.47 ± 172.443

Change from Baseline in Fecal Calprotectin

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

ANCOVA

Parameter type

LS Mean difference (Final Values)

Point estimate

-839.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1323.08

upper limit

-356.21

Variability estimate

Standard error of the mean

Dispersion value

245.99

Notes
[10] - ANCOVA with modified baseline observation carried forward (mBOCF).

Secondary: Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS)

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End point title

Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) ^[11]

End point description

The Urgency NRS is a single participant reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). Higher scores indicate more severe urgency. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), clinical remission status (yes/no) at AMAN Week 12, and region (North America/Europe/Other). Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Induction Baseline, Week 40 APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline urgency NRS measurement.

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	104	316
Units: score on a scale
least squares mean (standard error)	-2.74 ± 0.202	-3.80 ± 0.139

Change From Baseline to Week 40 in NRS

Comparison groups

Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC) v Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC

Number of subjects included in analysis

420

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean difference (Final Values)

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

-0.61

Variability estimate

Standard error of the mean

Dispersion value

0.228

Secondary: Percentage of Participants Hospitalized for Ulcerative Colitis (UC)

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End point title

Percentage of Participants Hospitalized for Ulcerative Colitis (UC) ^[12]

End point description

Percentage of participants hospitalized for UC. Only hospitalizations associated with an adverse event with >=24 hours stay were recorded. APD: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

End point type

Secondary

End point timeframe

Week 40

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is reported only for randomized arms as described in the protocol.

End point values	Maintenance Period: Miri IR - Placebo (PBO) Subcutaneous (SC)	Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Number of subjects analysed	179	365
Units: percentage of participants
number (not applicable)	1.1	0

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK): Clearance of Mirikizumab

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End point title

Pharmacokinetics (PK): Clearance of Mirikizumab

End point description

Clearance of mirikizumab was evaluated. APD: All randomized participants who received at least one dose of study drug subcutaneously (both induction responders and nonresponders) and had evaluable PK data.

End point type

Secondary

End point timeframe

Predose: Weeks 0, 4, 12, 24 and 40

End point values	200 Milligram (mg) Miri SC
Number of subjects analysed	652
Units: Liters per Hour (L/h)
geometric mean (geometric coefficient of variation)	0.0487 ± 54

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up To 40 Weeks

Adverse event reporting additional description

All randomized participants who received at least one dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Maintenance Period: PBO IR - PBO SC

Reporting group description

Participants who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40.

Reporting group title

Maintenance Period: Miri IR - PBO SC

Reporting group description

Participants who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.

Reporting group title

Maintenance Period: Miri IR - 200 mg Miri SC

Reporting group description

Participants who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.

Reporting group title

Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV

Reporting group description

Participants who received blinded PBO SC or blinded 200 mg mirikizumab SC Q4W during maintenance period and experienced a loss of response at or after Week 12, received rescue therapy with open label 300 mg mirikizumab intravenous (IV) Q4W for 3 doses.

Reporting group title

Extended Induction: Induction Nonresponders - 300mg Miri IV

Reporting group description

Participants who were nonresponders to blinded mirikizumab or placebo in induction study (LUCENT-1), received additional 3 doses of open label 300 mg mirikizumab IV Q4W during extended induction period from Week 0 of LUCENT-2 until Week 12.

Reporting group title

Open Label Maintenance: Delayed Responders - 200 mg Miri SC

Reporting group description

Participants who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40 or until early termination (rescue was not available for these participants).

Serious adverse events	Maintenance Period: PBO IR - PBO SC	Maintenance Period: Miri IR - PBO SC	Maintenance Period: Miri IR - 200 mg Miri SC	Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV	Extended Induction: Induction Nonresponders - 300mg Miri IV	Open Label Maintenance: Delayed Responders - 200 mg Miri SC
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 135 (5.19%)	15 / 192 (7.81%)	13 / 389 (3.34%)	3 / 90 (3.33%)	21 / 461 (4.56%)	8 / 271 (2.95%)
number of deaths (all causes)	0	1	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
adenocarcinoma of colon
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastric cancer
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
kaposi's sarcoma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
lipoma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rectal cancer
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
deep vein thrombosis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
colectomy total
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
retinopexy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
tooth extraction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
anaphylactic reaction
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
rectocele
alternative dictionary used: MedDRA 24.1
subjects affected / exposed ^[1]	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 160 (0.63%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
depression suicidal
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
neurologic somatic symptom disorder
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	1 / 90 (1.11%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
blood glucose increased
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
brain contusion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
patella fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
road traffic accident
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
spinal compression fracture
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
acute coronary syndrome
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
ischaemic stroke
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
migraine
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
presyncope
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
immune thrombocytopenia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
maculopathy
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
retinal detachment
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
colitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
colitis ulcerative
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	6 / 192 (3.13%)	0 / 389 (0.00%)	1 / 90 (1.11%)	6 / 461 (1.30%)	2 / 271 (0.74%)
occurrences causally related to treatment / all	1 / 1	0 / 6	0 / 0	1 / 1	0 / 6	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ileus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
inguinal hernia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
large intestine perforation
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
peptic ulcer
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumoperitoneum
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rectal haemorrhage
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rectal polyp
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
pruritus
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
nephrolithiasis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ureterolithiasis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
autoimmune thyroiditis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	1 / 90 (1.11%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
back pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
intervertebral disc protrusion
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sacral pain
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
appendicitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
bacillus infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
covid-19
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
covid-19 pneumonia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
campylobacter gastroenteritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cellulitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cytomegalovirus colitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
diverticulitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
escherichia infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastroenteritis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
influenza
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
klebsiella infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
large intestine infection
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	1 / 135 (0.74%)	0 / 192 (0.00%)	0 / 389 (0.00%)	1 / 90 (1.11%)	2 / 461 (0.43%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	1 / 271 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
subcutaneous abscess
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
tonsillitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	0 / 389 (0.00%)	0 / 90 (0.00%)	1 / 461 (0.22%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
hypoglycaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	1 / 192 (0.52%)	0 / 389 (0.00%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypokalaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	0 / 135 (0.00%)	0 / 192 (0.00%)	1 / 389 (0.26%)	0 / 90 (0.00%)	0 / 461 (0.00%)	0 / 271 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Maintenance Period: PBO IR - PBO SC	Maintenance Period: Miri IR - PBO SC	Maintenance Period: Miri IR - 200 mg Miri SC	Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV	Extended Induction: Induction Nonresponders - 300mg Miri IV	Open Label Maintenance: Delayed Responders - 200 mg Miri SC
Total subjects affected by non serious adverse events
subjects affected / exposed	37 / 135 (27.41%)	57 / 192 (29.69%)	90 / 389 (23.14%)	13 / 90 (14.44%)	44 / 461 (9.54%)	54 / 271 (19.93%)
Nervous system disorders
headache
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	5 / 135 (3.70%)	2 / 192 (1.04%)	16 / 389 (4.11%)	5 / 90 (5.56%)	8 / 461 (1.74%)	13 / 271 (4.80%)
occurrences all number	18	5	21	5	10	21
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	8 / 135 (5.93%)	9 / 192 (4.69%)	8 / 389 (2.06%)	5 / 90 (5.56%)	7 / 461 (1.52%)	9 / 271 (3.32%)
occurrences all number	11	12	8	5	7	9
Gastrointestinal disorders
colitis ulcerative
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	17 / 135 (12.59%)	35 / 192 (18.23%)	26 / 389 (6.68%)	0 / 90 (0.00%)	4 / 461 (0.87%)	10 / 271 (3.69%)
occurrences all number	18	35	30	0	4	11
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	4 / 135 (2.96%)	8 / 192 (4.17%)	26 / 389 (6.68%)	3 / 90 (3.33%)	15 / 461 (3.25%)	19 / 271 (7.01%)
occurrences all number	4	8	27	5	15	24
Infections and infestations
nasopharyngitis
alternative dictionary used: MedDRA 24.1
subjects affected / exposed	9 / 135 (6.67%)	11 / 192 (5.73%)	28 / 389 (7.20%)	1 / 90 (1.11%)	15 / 461 (3.25%)	14 / 271 (5.17%)
occurrences all number	12	11	38	1	15	15

More information

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Were there any global substantial amendments to the protocol? Yes

12 Sep 2019

• Replaced Primary objective, major secondary objectives, added Other secondary objectives • Added: 50% biological 50% conventional failure split • Follicle stimulating hormone (FSH) testing optional in women to confirm nonchild-bearing potential • Clarified infusion-reaction related samples • Clarified collection of Endoscopy • Clarified conditions when patients perform health outcome assessments • Clarified when informed consent form (ICF) be obtained • Clarified schedule of activities • Minimized study procedures for participants • Visit window changed between AMAN and AMBG • Clarification of Inclusion Criteria • Added assessments if drug hypersensitivity event observed • Changed the term Study treatment to study drug as study drug is blinded • Clarified term “mucosal healing” • Primary endpoint terminology changed from “durable clinical remission” to “clinical remission”; “remission changed to response” with mirikizumab induction treatment for clarification of treatment • Text deleted for medical monitor consult for endoscopy findings • Added when early termination visit (ETV) endoscopy should be discussed with the medical monitor. • Added Centers for Disease Control and Prevention guidance (CDC) was for the United States (US) and the World Health Organization (WHO) was for countries outside of the US • Deleted clinical study report (CSR) coordinating investigator “with the most enrolled participant's” will be selected by the study team • Clarified use of permitted and prohibited Medications

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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