NCT02065557 · OUTCOME

Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period

Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis · Source last updated 2020-10-05

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: NUMBER
Unit: percentage of participants
Interval / dispersion: 95% Confidence Interval
Time frame: Week 52

What was measured

The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those participants with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Mucosal healing per Mayo endoscopy subscore is defined as a subscore of ≤ 1.

Analysis population: Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. NRI: missing data is imputed as not having met the endpoint.

Groups in this outcome

Main Study: M-PL

(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.

Main Study: M-SD

Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg \[maximum dose of 40 mg\] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.

Main Study: M-HD

Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg \[maximum dose of 40 mg\] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.

Main Study: M-SD + M-HD

Combined M-SD + M-HD arms (see above).

Integrated Study (Main + Japan Sub-Study): M-PL

Integrated Study (Main + Japan Sub-Study): M-SD

Integrated Study (Main + Japan Sub-Study): M-HD

Integrated Study (Main + Japan Sub-Study): M-SD + M-HD

Combined M-SD + M-HD arms (see above).

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

Group	Source count
Main Study: M-PL	12
Main Study: M-SD	31
Main Study: M-HD	31
Main Study: M-SD + M-HD	62
Integrated Study (Main + Japan Sub-Study): M-PL	12
Integrated Study (Main + Japan Sub-Study): M-SD	33
Integrated Study (Main + Japan Sub-Study): M-HD	35
Integrated Study (Main + Japan Sub-Study): M-SD + M-HD	68

Reported measurements

Source class 1

Values in percentage of participants · Interval/dispersion: 95% Confidence Interval
Group	Value	Spread	Lower	Upper	Comment
Main Study: M-PL	33.3	Not reported	9.92	65.11	Not reported
Main Study: M-SD	38.7	Not reported	21.85	57.81	Not reported
Main Study: M-HD	51.6	Not reported	33.06	69.85	Not reported
Main Study: M-SD + M-HD	45.2	Not reported	32.48	58.32	Not reported
Integrated Study (Main + Japan Sub-Study): M-PL	33.3	Not reported	9.92	65.11	Not reported
Integrated Study (Main + Japan Sub-Study): M-SD	36.4	Not reported	20.40	54.88	Not reported
Integrated Study (Main + Japan Sub-Study): M-HD	48.6	Not reported	31.38	66.01	Not reported
Integrated Study (Main + Japan Sub-Study): M-SD + M-HD	42.6	Not reported	30.72	55.23	Not reported

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG003
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG002
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG001
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
0.382
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG007
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG006
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG005
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
0.344
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure

Complete source fields

analyses

group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG003
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG002
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG001
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
0.382
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG007
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG006
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
< 0.001
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure
group Description
Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
group Ids
OG005
non Inferiority Comment
one-sample two-sided Chi-square test
non Inferiority Type
SUPERIORITY
p Value
0.344
p Value Comment
Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
statistical Comment
controlling familywise Type I error of 5% in a strong sense
statistical Method
rejective multiple test procedure

classes

categories
measurements
group Id
OG000
lower Limit
9.92
upper Limit
65.11
value
33.3
group Id
OG001
lower Limit
21.85
upper Limit
57.81
value
38.7
group Id
OG002
lower Limit
33.06
upper Limit
69.85
value
51.6
group Id
OG003
lower Limit
32.48
upper Limit
58.32
value
45.2
group Id
OG004
lower Limit
9.92
upper Limit
65.11
value
33.3
group Id
OG005
lower Limit
20.40
upper Limit
54.88
value
36.4
group Id
OG006
lower Limit
31.38
upper Limit
66.01
value
48.6
group Id
OG007
lower Limit
30.72
upper Limit
55.23
value
42.6

denoms

counts
group Id
OG000
value
12
group Id
OG001
value
31
group Id
OG002
value
31
group Id
OG003
value
62
group Id
OG004
value
12
group Id
OG005
value
33
group Id
OG006
value
35
group Id
OG007
value
68
units
Participants

description

dispersion Type

95% Confidence Interval

groups

description
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
id
OG000
title
Main Study: M-PL
description
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg \[maximum dose of 40 mg\] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
id
OG001
title
Main Study: M-SD
description
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg \[maximum dose of 40 mg\] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
id
OG002
title
Main Study: M-HD
description
Combined M-SD + M-HD arms (see above).
id
OG003
title
Main Study: M-SD + M-HD
description
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
id
OG004
title
Integrated Study (Main + Japan Sub-Study): M-PL
description
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg \[maximum dose of 40 mg\] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
id
OG005
title
Integrated Study (Main + Japan Sub-Study): M-SD
description
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg \[maximum dose of 40 mg\] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
id
OG006
title
Integrated Study (Main + Japan Sub-Study): M-HD
description
Combined M-SD + M-HD arms (see above).
id
OG007
title
Integrated Study (Main + Japan Sub-Study): M-SD + M-HD

param Type

NUMBER

population Description

Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. NRI: missing data is imputed as not having met the endpoint.

reporting Status

POSTED

time Frame

Week 52

title

Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period

type

SECONDARY

unit Of Measure

percentage of participants

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Preserved source evidence · Not medical advice