Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43865 clinical trials with a EudraCT protocol, of which 7286 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A Multicenter, Randomized, Double-Dummy, Double-Blind Study Evaluating Two Doses of Adalimumab versus Methotrexate (MTX) in Pediatric Subjects with Chronic Plaque Psoriasis (Ps)

Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.

Summary
EudraCT number	2009-013072-52
Trial protocol	DE BE ES CZ HU IT Outside EU/EEA NL
Global end of trial date	03 Feb 2015

Results information
Results version number	v1(current)
This version publication date	18 May 2016
First version publication date	18 May 2016
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

M04-717

ISRCTN number

-

US NCT number

NCT01251614

WHO universal trial number (UTN)

-

Sponsor organisation name

AbbVie

Sponsor organisation address

1 North Waukegan Road, North Chicago, IL, United States, 60064

Public contact

Global Medical Information, AbbVie, 001 800-633-9110,

Scientific contact

David A Williams, AbbVie, david.a.williams@abbvie.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000366-PIP01-08

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

Final

Date of interim/final analysis

03 Feb 2015

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

03 Feb 2015

Was the trial ended prematurely?

No

Main objective of the trial

The objectives of this study were to determine the safety and efficacy of 2 doses of adalimumab versus MTX in pediatric subjects with severe chronic plaque psoriasis, to determine the time to loss of disease control, the ability to regain response upon re-treatment, and to examine the pharmacokinetics (PK) and immunogenicity of adalimumab following subcutaneous (SC) administration in this subject population.

Protection of trial subjects

The investigator or his/her representative explained the nature of the study to the subject and the subject's parent/legal guardian, and answered all questions regarding this study. Paediatric subjects were included in all discussions in order to obtain verbal or written assent. Prior to any study-related screening procedures being performed on the subject, the informed consent statement was reviewed and signed and dated by the subject's parent/legal guardian and the person who administered the informed consent, and any other signatories according to local requirements.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

14 Dec 2010

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Chile: 5

Country: Number of subjects enrolled

Poland: 28

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Belgium: 6

Country: Number of subjects enrolled

Czech Republic: 4

Country: Number of subjects enrolled

Germany: 11

Country: Number of subjects enrolled

Hungary: 8

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Mexico: 5

Country: Number of subjects enrolled

Switzerland: 4

Country: Number of subjects enrolled

Turkey: 3

Country: Number of subjects enrolled

Canada: 28

Worldwide total number of subjects

114

EEA total number of subjects

69

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)

42

Adolescents (12-17 years)

61

Adults (18-64 years)

11

From 65 to 84 years

0

85 years and over

0

Subject disposition

Top of page

Recruitment details

-

Screening details

Subjects were to be children (from 4 to 11 years of age) and adolescents (from 12 through 17 years of age) with a clinical diagnosis of Ps for at least 6 months. Eligible subjects must have failed topical therapy and required systemic therapy to control their disease.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Methotrexate

Arm description

Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Arm type

Active comparator

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Methotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally.

Investigational medicinal product name

Adalimumab Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

A single SC loading dose at Week 0 followed by eow dosing beginning at Week 1.

Adalimumab 0.4 mg/kg

Arm description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

Arm type

Experimental

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab by subcutaneous injection every other week (EOW)

Investigational medicinal product name

Methotrexate placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Orally once a week

Adalimumab 0.8 mg/kg

Arm description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Arm type

Experimental

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Humira

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab by subcutaneous injection every other week (EOW)

Investigational medicinal product name

Methotrexate placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Orally once a week

Number of subjects in period 1	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Started	37	39	38
Entered Period B	13 ^[1]	18 ^[2]	23 ^[3]
Entered Period C	8 ^[4]	11 ^[5]	19 ^[6]
Entered Period D	36	36	36
Completed	34	26	30
Not completed	3	13	8
Consent withdrawn by subject	-	2	1
Loss of disease control	-	1	-
Pregnancy	-	-	2
Adverse event	1	-	1
Lost to follow-up	-	1	-
Lack of efficacy	1	9	4
Almost total clearing of psoriatic lesions	1	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)

Baseline characteristics

Top of page

Reporting group title

Methotrexate

Reporting group description

Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Reporting group title

Adalimumab 0.4 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

Reporting group title

Adalimumab 0.8 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Reporting group values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg	Total
Number of subjects	37	39	38	114
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	13.4 ( 3.49 )	12.6 ( 4.43 )	13 ( 3.29 )	-
Gender categorical
Units: Subjects
Female	26	18	21	65
Male	11	21	17	49

End points

Top of page

Reporting group title

Methotrexate

Reporting group description

Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Reporting group title

Adalimumab 0.4 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

Reporting group title

Adalimumab 0.8 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Primary: Percentage of Subjects Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16

Top of page

End point title

Percentage of Subjects Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Primary

End point timeframe

Baseline and Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)	32.4	43.6	57.9

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Methotrexate v Adalimumab 0.8 mg/kg

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.027

Method

Chi-squared

Parameter type

Difference

Point estimate

-25.5

Confidence interval

level

95%

sides

2-sided

lower limit

-47.2

upper limit

-3.7

Notes
[1] - The a priori defined order of the statistical hypotheses was as follows: 1. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a ≥ PASI 75 response at Week 16. 2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a PGA cleared or minimal at Week 16. This order was adhered to for confirmatory testing, all statistical tests were to be done at a level of significance of 5% and the overall type I error was preserved.

Primary: Percentage of Subjects Achieving a Physician’s Global Assessment of Disease Activity (PGA) of "Cleared" or "Minimal" (0 or 1) at Week 16

Top of page

End point title

Percentage of Subjects Achieving a Physician’s Global Assessment of Disease Activity (PGA) of "Cleared" or "Minimal" (0 or 1) at Week 16

End point description

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.

End point type

Primary

End point timeframe

Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)	40.5	41	60.5

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Methotrexate v Adalimumab 0.8 mg/kg

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.083

Method

Chi-squared

Parameter type

Difference

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-42.2

upper limit

2.2

Notes
[2] - The a priori defined order of the statistical hypotheses was as follows: 1. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a ≥ PASI 75 response at Week 16. 2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a PGA cleared or minimal at Week 16. This order was adhered to for confirmatory testing, all statistical tests were to be done at a level of significance of 5% and the overall type I error was preserved.

Secondary: Percentage of Subjects Who Achieved a PASI 90 Response at Week 16

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 90 Response at Week 16

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)	21.6	30.8	28.9

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Adalimumab 0.8 mg/kg v Methotrexate

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.466

Method

Chi-squared

Parameter type

Difference

Point estimate

-7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-26.9

upper limit

12.3

Notes
[3] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Secondary: Percentage of Subjects Who Achieved a PASI 100 Response at Week 16

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 100 Response at Week 16

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-100 response is the percentage of participants who achieved a 100% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)	2.7	10.3	18.4

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Adalimumab 0.8 mg/kg v Methotrexate

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.056

Method

Fisher exact

Parameter type

Difference

Point estimate

-15.7

Confidence interval

level

95%

sides

2-sided

lower limit

-29.1

upper limit

-2.3

Notes
[4] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Secondary: Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Scores at Week 16

Top of page

End point title

Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Scores at Week 16

End point description

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Last observation carried forward (LOCF) imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	36	38	38
Units: units on a scale
arithmetic mean (standard deviation)	-5 ( 7.11 )	-4.9 ( 6.16 )	-6.6 ( 6.22 )

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Methotrexate v Adalimumab 0.8 mg/kg

Number of subjects included in analysis

74

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.304

Method

ANOVA

Parameter type

Difference

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

4.7

Notes
[5] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Secondary: Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16

Top of page

End point title

Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16

End point description

The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	38	38
Units: units on a scale
arithmetic mean (standard deviation)	1.9 ( 10.41 )	9.5 ( 12.25 )	10.8 ( 15.38 )

Adalimumab 0.8 mg/kg versus MTX

Comparison groups

Adalimumab 0.8 mg/kg v Methotrexate

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.005

Method

ANOVA

Parameter type

Difference

Point estimate

-8.88

Confidence interval

level

95%

sides

2-sided

lower limit

-14.94

upper limit

-2.82

Notes
[6] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Secondary: Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Upon Re-Treatment in Period C

Top of page

End point title

Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Upon Re-Treatment in Period C

End point description

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.

End point type

Secondary

End point timeframe

Period C, Week 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	8 ^[7]	11 ^[8]	19 ^[9]
Units: percentage of subjects
number (not applicable)	62.5	27.3	52.6

Notes
[7] - Subjects in Period C
[8] - Subjects in Period C
[9] - Subjects in Period C

Adalimumab 0.8mg/kg + MTX vs Adalimuimab 0.4 mg/kg

Statistical analysis description

The difference between the combined adalimumab 0.8 mg/kg + MTX groups and the adalimumab 0.4 mg/kg group.

Comparison groups

Adalimumab 0.8 mg/kg v Adalimumab 0.4 mg/kg v Methotrexate

Number of subjects included in analysis

38

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.113

Method

Chi-squared

Parameter type

Difference

Point estimate

-28.3

Confidence interval

level

95%

sides

2-sided

lower limit

-60.6

upper limit

4

Notes
[10] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Secondary: Time to Loss of Disease Control in Period B

Top of page

End point title

Time to Loss of Disease Control in Period B

End point description

Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation). This analysis was conducted in the ITT population, no imputation was used.

End point type

Secondary

End point timeframe

Period B - 36 weeks

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	13 ^[11]	18 ^[12]	23 ^[13]
Units: days
median (inter-quartile range (Q1-Q3))	184 (84 to 335)	217 (56 to 551)	118 (79 to 194)

Notes
[11] - Subjects in Period B
[12] - Subjects in Period B
[13] - Subjects in Period B

Adalimumab 0.8 mg/kg versus MTX

Statistical analysis description

Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Comparison groups

Adalimumab 0.8 mg/kg v Methotrexate

Number of subjects included in analysis

36

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.343

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

3.17

Adalimumab 0.8 mg/kg versus Adalimumab 0.4 mg/kg

Statistical analysis description

Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

Comparison groups

Adalimumab 0.8 mg/kg v Adalimumab 0.4 mg/kg

Number of subjects included in analysis

41

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.276

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

3.21

Secondary: Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Over Time

Top of page

End point title

Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Over Time

End point description

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	8.1	20.5	28.9
Period A, Week 8	8.1	35.9	44.7
Period A, Week 11	18.9	30.8	47.4
Period C, Week 0 (n=8, 11, 19)	0	0	0
Period C, Week 16 (n=8, 11, 19)	62.5	27.3	52.6
Period D, Week 0 (n=36, 36, 36)	30.6	19.4	38.9
Period D, Week 16 (n=36, 36, 36)	77.8	38.9	50
Period D, Week 28 (n=36, 36, 36)	69.4	50	63.9
Period D, Week 40 (n=36, 36, 36)	69.4	50	61.1
Period D, Week 52 (n=36, 36, 36)	75	50	55.6

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving a PGA of "Cleared" (0) Over Time

Top of page

End point title

Percentage of Subjects Achieving a PGA of "Cleared" (0) Over Time

End point description

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	0	2.6	2.6
Period A, Week 8	0	12.8	5.3
Period A, Week 11	0	10.3	10.5
Period C, Week 0 (n=8, 11, 19)	0	0	0
Period C, Week 16 (n=8, 11, 19)	25	9.1	15.8
Period D, Week 0 (n=36, 36, 36)	8.3	5.6	11.1
Period D, Week 16 (n=36, 36, 36)	25	11.1	25
Period D, Week 28 (n=36, 36, 36)	33.3	16.7	22.2
Period D, Week 40 (n=36, 36, 36)	33.3	16.7	27.8
Period D, Week 52 (n=36, 36, 36)	41.7	25	25

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved a PASI 50 Response Over Time

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 50 Response Over Time

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	16.2	41	52.6
Period A, Week 8	40.5	56.4	65.8
Period A, Week 11	51.4	61.5	71.1
Period A, Week 16	54.1	66.7	78.9
Period C, Week 0 (n=8, 11, 19)	62.5	90.9	52.6
Period C, Week 16 (n=8, 11, 19)	87.5	90.9	89.5
Period D, Week 0 (n=36, 36, 36)	52.8	63.9	75
Period D, Week 16 (n=36, 36, 36)	91.7	69.4	88.9
Period D, Week 28 (n=36, 36, 36)	88.9	72.2	86.1
Period D, Week 40 (n=36, 36, 36)	91.7	63.9	83.3
Period D, Week 52 (n=36, 36, 36)	91.7	66.7	77.8

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved a PASI 75 Response Over Time

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 75 Response Over Time

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	0	15.4	23.7
Period A, Week 8	13.5	38.5	47.4
Period A, Week 11	21.6	43.6	60.5
Period C, Week 0 (n=8, 11, 19)	37.5	18.2	21.1
Period C, Week 16 (n=8, 11, 19)	75	54.5	78.9
Period D, Week 0 (n=36, 36, 36)	30.6	27.8	50
Period D, Week 16 (n=36, 36, 36)	86.1	50	61.1
Period D, Week 28 (n=36, 36, 36)	80.6	58.3	77.8
Period D, Week 40 (n=36, 36, 36)	77.8	52.8	75
Period D, Week 52 (n=36, 36, 36)	86.1	47.2	72.2

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved a PASI 90 Response Over Time

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 90 Response Over Time

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	0	5.1	5.3
Period A, Week 8	2.7	20.5	23.7
Period A, Week 11	2.7	28.2	28.9
Period C, Week 0 (n=8, 11, 19)	0	0	10.5
Period C, Week 16 (n=8, 11, 19)	62.5	27.3	57.9
Period D, Week 0 (n=36, 36, 36)	25	16.7	36.1
Period D, Week 16 (n=36, 36, 36)	63.9	36.1	38.9
Period D, Week 28 (n=36, 36, 36)	55.6	33.3	41.7
Period D, Week 40 (n=36, 36, 36)	55.6	36.1	47.2
Period D, Week 52 (n=36, 36, 36)	66.7	33.3	44.4

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieved a PASI 100 Response Over Time

Top of page

End point title

Percentage of Subjects Who Achieved a PASI 100 Response Over Time

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-100 response is the percentage of participants who achieved a 100% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	0	0	2.6
Period A, Week 8	0	5.1	5.3
Period A, Week 11	0	5.1	10.5
Period C, Week 0 (n=8, 11, 19)	0	0	0
Period C, Week 16 (n=8, 11, 19)	25	9.1	15.8
Period D, Week 0 (n=36, 36, 36)	8.3	5.6	11.1
Period D, Week 16 (n=36, 36, 36)	13.9	11.1	25
Period D, Week 28 (n=36, 36, 36)	27.8	13.9	19.4
Period D, Week 40 (n=36, 36, 36)	30.6	13.9	22.2
Period D, Week 52 (n=36, 36, 36)	41.7	25	22.2

No statistical analyses for this end point

Secondary: Percent Change From Baseline in PASI Score Over Time

Top of page

End point title

Percent Change From Baseline in PASI Score Over Time

End point description

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percent change
arithmetic mean (standard deviation)
Period A, Week 4	-14 ( 36.71 )	-36.9 ( 38.62 )	-48.3 ( 33.96 )
Period A, Week 8	-30.6 ( 45.89 )	-48.8 ( 44.74 )	-60.3 ( 35.98 )
Period A, Week 11	-36.6 ( 51.69 )	-51.4 ( 50.19 )	-62.8 ( 38.02 )
Period A, Week 16	-42.8 ( 54.24 )	-52.4 ( 51.79 )	-65.6 ( 39.44 )
Period C, Week 0 (n=8, 11, 19)	-59 ( 20.61 )	-65.3 ( 12.16 )	-45.8 ( 39.64 )
Period C, Week 16 (n=8, 11, 19)	-87.1 ( 16.47 )	-74.5 ( 17.79 )	-69.3 ( 69.79 )
Period D, Week 0 (n=36, 36, 36)	-41.8 ( 54.99 )	-46.8 ( 49.27 )	-61.5 ( 42.96 )
Period D, Week 16 (n=36, 36, 36)	-82.3 ( 31.38 )	-66.9 ( 33.51 )	-74.5 ( 37.44 )
Period D, Week 28 (n=36, 36, 36)	-81 ( 35.86 )	-65.8 ( 36.99 )	-81.5 ( 22.06 )
Period D, Week 40 (n=36, 36, 36)	-83 ( 31.94 )	-64.6 ( 37.46 )	-82.1 ( 23.99 )
Period D, Week 52 (n=36, 36, 36)	-86.3 ( 28.92 )	-58.7 ( 53.21 )	-80.1 ( 24.17 )

No statistical analyses for this end point

Secondary: Change From Baseline in CDLQI Over Time

Top of page

End point title

Change From Baseline in CDLQI Over Time

End point description

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline, Period A, Weeks 4, and 8 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	36	38	38
Units: units on a scale
arithmetic mean (standard deviation)
Period A, Week 4	-2.9 ( 5.24 )	-3.9 ( 5.22 )	-4.9 ( 5.8 )
Period A, Week 8	-4 ( 6.44 )	-4.1 ( 6.29 )	-5.5 ( 5.66 )
Period C, Week 0 (n=8, 11, 19)	-6.1 ( 4.55 )	-4.7 ( 9.08 )	-6.1 ( 6.92 )
Period C, Week 4 (n=8, 11, 19)	-9.8 ( 3.92 )	-5.5 ( 7.24 )	-7 ( 6.63 )
Period D, Week 0 (n=35, 35, 36)	-5.6 ( 7.55 )	-5.5 ( 5.95 )	-6.8 ( 6.7 )
Period D, Week 11 (n=35, 35, 36)	-8.5 ( 5.37 )	-6.8 ( 7.07 )	-7.4 ( 6.21 )
Period D, Week 28 (n=35, 35, 36)	-8.3 ( 5.93 )	-6.8 ( 7.91 )	-8.4 ( 6.72 )
Period D, Week 52 (n=35, 35, 36)	-8.4 ( 6.08 )	-6.6 ( 8.12 )	-8.2 ( 6.75 )

No statistical analyses for this end point

Secondary: Percentage of Subjects With CDLQI = 0 Over Time

Top of page

End point title

Percentage of Subjects With CDLQI = 0 Over Time

End point description

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life. Non-responder imputation was used, the analysis was conducted in the intent to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8 and 16 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: percentage of subjects
number (not applicable)
Period A, Week 4	5.4	5.1	10.5
Period A, Week 8	10.8	12.8	5.3
Period A, Week 16	10.8	20.5	23.7
Period C, Week 0 (n=8, 11, 19)	0	36.4	21.1
Period C, Week 4 (n=8, 11, 19)	12.5	36.4	31.6
Period D, Week 0 (n=36, 36, 36)	16.7	22.2	27.8
Period D, Week 11 (n=36, 36, 36)	25	16.7	33.3
Period D, Week 28 (n=36, 36, 36)	30.6	22.2	30.6
Period D, Week 52 (n=36, 36, 36)	41.7	16.7	33.3

No statistical analyses for this end point

Secondary: Time to PASI 50/75/90/100 Response in Period A

Top of page

End point title

Time to PASI 50/75/90/100 Response in Period A

End point description

Subjects who did not have a response during Period A were censored. "99999" indicates parameters that were not estimable.

End point type

Secondary

End point timeframe

Period A, 16 weeks

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	39	38
Units: days
median (inter-quartile range (Q1-Q3))
PASI 50	76 (56 to 112)	55 (28 to 115)	30 (28 to 77)
PASI 75	116 (111 to 99999)	107 (56 to 99999)	59 (53 to 99999)
PASI 90	99999 (112 to 99999)	99999 (78 to 99999)	99999 (76 to 99999)
PASI 100	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Change From Baseline in PedsQL Over Time

Top of page

End point title

Change From Baseline in PedsQL Over Time

End point description

The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline, Period A, Weeks 4 and 8 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	37	38	38
Units: units on a scale
arithmetic mean (standard deviation)
Period A, Week 4 (n=37, 38, 36)	-0.8 ( 11.75 )	4.9 ( 13.8 )	8.1 ( 11.95 )
Period A, Week 8 (n=37, 38, 38)	0.5 ( 10.18 )	7 ( 13.16 )	8.8 ( 15.45 )
Period C, Week 0 (n=8, 11, 19)	3 ( 10.45 )	8.9 ( 25.35 )	14.2 ( 20.25 )
Period C, Week 4 (n=8, 11, 19)	5.2 ( 11.08 )	11.6 ( 25.19 )	16.3 ( 17.35 )
Period D, Week 0 (n=36, 36, 36)	2.3 ( 10.93 )	9.4 ( 16.9 )	10.5 ( 15.86 )
Period D, Week 11 (n=36, 36, 36)	5.4 ( 10.36 )	12.8 ( 19.03 )	12 ( 16.13 )
Period D, Week 28 (n=36, 36, 36)	8 ( 13.4 )	14.5 ( 20.19 )	13.1 ( 16.23 )
Period D, Week 52 (n=36, 36, 36)	8.6 ( 13.93 )	14 ( 20.4 )	13.8 ( 15.36 )

No statistical analyses for this end point

Secondary: Change From Baseline in the Children's Depression Inventory: Short (CDI:S)

Top of page

End point title

Change From Baseline in the Children's Depression Inventory: Short (CDI:S)

End point description

The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms. LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Period A, Weeks 4, 8, and 16

End point values	Methotrexate	Adalimumab 0.4 mg/kg	Adalimumab 0.8 mg/kg
Number of subjects analysed	35	35	35
Units: units on a scale
arithmetic mean (standard deviation)
Period A, Week 4 (n=35, 35, 34)	0.6 ( 8.85 )	-1 ( 6.64 )	-3.6 ( 5.86 )
Period A, Week 8 (n=35, 35, 34)	0.2 ( 5.26 )	-1.5 ( 7.52 )	-1.6 ( 5.52 )
Period A, Week 16 (n=35, 35, 35)	-2 ( 5.88 )	-3.3 ( 8.12 )	-2.3 ( 6.29 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Period A - up to 16 weeks Period B - up to 36 weeks Period C - up to 16 weeks Period D - up to 52 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Period A: Methotrexate

Reporting group description

Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week dosing from Week 1.

Reporting group title

Period A: Adalimumab 0.4 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab (ADA) 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets.

Reporting group title

Period A: Adalimumab 0.8 mg/kg

Reporting group description

In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets.

Reporting group title

Period B: MTX/No Treatment

Reporting group description

Subjects initially randomized to methotrexate who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

Reporting group title

Period B: ADA 0.4 mg/kg/No Treatment

Reporting group description

Subjects initially randomized to adalimumab (ADA) 0.4 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

Reporting group title

Period B: ADA 0.8 mg/kg/No Treatment

Reporting group description

Subjects initially randomized to adalimumab (ADA) 0.8 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

Reporting group title

Period C: Adalimumab 0.4 mg/kg

Reporting group description

Subjects initially randomized to adalimumab 0.4 mg/kg with loss of disease control in Period B received adalimumab 0.4 mg/kg eow for up to 16 weeks in Period C.

Reporting group title

Period C: Adalimumab 0.8 mg/kg

Reporting group description

Subjects initially randomized to either methotrexate or adalimumab 0.8 mg/kg with loss of disease control in Period B received adalimumab 0.8 mg/kg eow for up to 16 weeks in Period C.

Reporting group title

Period D: Adalimumab 0.4 mg/kg

Reporting group description

Subjects received adalimumab 0.4 mg/kg eow for up to 52 weeks in Period D.

Reporting group title

Period D: Adalimumab 0.8 mg/kg

Reporting group description

Subjects received adalimumab 0.8 mg/kg eow for up to 52 weeks in Period D.

Serious adverse events	Period A: Methotrexate	Period A: Adalimumab 0.4 mg/kg	Period A: Adalimumab 0.8 mg/kg	Period B: MTX/No Treatment	Period B: ADA 0.4 mg/kg/No Treatment	Period B: ADA 0.8 mg/kg/No Treatment	Period C: Adalimumab 0.4 mg/kg	Period C: Adalimumab 0.8 mg/kg	Period D: Adalimumab 0.4 mg/kg	Period D: Adalimumab 0.8 mg/kg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 37 (0.00%)	3 / 39 (7.69%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	5 / 87 (5.75%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Eye Naevus
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 1
Hand Fracture
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Tendon Injury
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest Pain
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Haemorrhagic Ovarian Cyst
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastrointestinal Infection
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Period A: Methotrexate	Period A: Adalimumab 0.4 mg/kg	Period A: Adalimumab 0.8 mg/kg	Period B: MTX/No Treatment	Period B: ADA 0.4 mg/kg/No Treatment	Period B: ADA 0.8 mg/kg/No Treatment	Period C: Adalimumab 0.4 mg/kg	Period C: Adalimumab 0.8 mg/kg	Period D: Adalimumab 0.4 mg/kg	Period D: Adalimumab 0.8 mg/kg
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 37 (62.16%)	27 / 39 (69.23%)	23 / 38 (60.53%)	6 / 13 (46.15%)	6 / 18 (33.33%)	6 / 23 (26.09%)	5 / 11 (45.45%)	16 / 27 (59.26%)	8 / 13 (61.54%)	64 / 87 (73.56%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 13 (0.00%)	4 / 87 (4.60%)
occurrences all number	0	1	0	1	0	1	0	2	0	7
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	1 / 18 (5.56%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)
occurrences all number	1	0	0	0	1	0	0	0	0	3
Joint Injury
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Laceration
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Thermal Burn
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	4 / 37 (10.81%)	7 / 39 (17.95%)	6 / 38 (15.79%)	1 / 13 (7.69%)	2 / 18 (11.11%)	1 / 23 (4.35%)	0 / 11 (0.00%)	3 / 27 (11.11%)	1 / 13 (7.69%)	22 / 87 (25.29%)
occurrences all number	8	11	7	1	2	3	0	3	1	30
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 37 (2.70%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0
Chest Pain
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	2	0	0	0	0	0	0	0	0	1
Fatigue
subjects affected / exposed	2 / 37 (5.41%)	4 / 39 (10.26%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 13 (0.00%)	4 / 87 (4.60%)
occurrences all number	2	4	0	0	0	0	0	3	0	4
Injection Site Pain
subjects affected / exposed	3 / 37 (8.11%)	1 / 39 (2.56%)	3 / 38 (7.89%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	3	1	3	0	0	0	0	1	0	1
Injection Site Reaction
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	2 / 38 (5.26%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1	2	0	0	0	0	1	0	3
Pyrexia
subjects affected / exposed	1 / 37 (2.70%)	3 / 39 (7.69%)	1 / 38 (2.63%)	0 / 13 (0.00%)	1 / 18 (5.56%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	4 / 87 (4.60%)
occurrences all number	1	3	1	0	1	0	0	0	1	5
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	4 / 37 (10.81%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	4 / 87 (4.60%)
occurrences all number	4	1	1	0	0	0	0	0	0	4
Abdominal Pain Upper
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	6 / 87 (6.90%)
occurrences all number	0	5	1	0	0	1	0	0	0	7
Diarrhoea
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	6 / 87 (6.90%)
occurrences all number	0	1	0	0	0	0	0	1	0	6
Dyspepsia
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	4 / 37 (10.81%)	3 / 39 (7.69%)	2 / 38 (5.26%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	1 / 13 (7.69%)	10 / 87 (11.49%)
occurrences all number	5	3	2	0	0	0	0	2	1	11
Vomiting
subjects affected / exposed	0 / 37 (0.00%)	3 / 39 (7.69%)	1 / 38 (2.63%)	0 / 13 (0.00%)	1 / 18 (5.56%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 13 (0.00%)	3 / 87 (3.45%)
occurrences all number	0	3	1	0	1	0	0	2	0	5
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	1	0	0	1	0	0	0	0	0	1
Cough
subjects affected / exposed	1 / 37 (2.70%)	4 / 39 (10.26%)	1 / 38 (2.63%)	0 / 13 (0.00%)	2 / 18 (11.11%)	0 / 23 (0.00%)	2 / 11 (18.18%)	1 / 27 (3.70%)	1 / 13 (7.69%)	4 / 87 (4.60%)
occurrences all number	1	4	1	0	2	0	2	1	1	4
Dyspnoea
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0
Epistaxis
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	3 / 87 (3.45%)
occurrences all number	0	0	0	0	0	0	0	0	1	4
Oropharyngeal Pain
subjects affected / exposed	2 / 37 (5.41%)	1 / 39 (2.56%)	2 / 38 (5.26%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	6 / 87 (6.90%)
occurrences all number	2	1	2	0	0	0	0	1	0	7
Rhinorrhoea
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 13 (0.00%)	1 / 18 (5.56%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	1 / 87 (1.15%)
occurrences all number	0	1	1	0	1	0	0	0	1	1
Skin and subcutaneous tissue disorders
Dry Skin
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	3 / 38 (7.89%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	3	0	0	0	0	1	0	0
Eczema
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	1 / 38 (2.63%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	4 / 87 (4.60%)
occurrences all number	0	2	1	1	0	0	0	0	0	7
Eczema Vesicular
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	1 / 37 (2.70%)	3 / 39 (7.69%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	1 / 27 (3.70%)	0 / 13 (0.00%)	4 / 87 (4.60%)
occurrences all number	1	3	1	0	0	0	2	1	0	4
Pruritus Generalised
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	0	0	0	0	0	1	0	0	1
Psoriasis
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	6 / 87 (6.90%)
occurrences all number	1	1	1	0	0	1	0	0	1	6
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Insomnia
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 37 (5.41%)	1 / 39 (2.56%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)
occurrences all number	2	1	1	0	0	1	0	0	0	4
Back Pain
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	2 / 38 (5.26%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	3 / 27 (11.11%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	2	2	0	0	0	0	3	0	2
Joint Effusion
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Musculoskeletal Pain
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	1 / 18 (5.56%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	5 / 87 (5.75%)
occurrences all number	0	0	0	0	0	1	0	1	0	6
Gastroenteritis
subjects affected / exposed	3 / 37 (8.11%)	0 / 39 (0.00%)	2 / 38 (5.26%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	3	0	2	0	0	0	1	0	0	1
Influenza
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	9 / 87 (10.34%)
occurrences all number	0	0	1	0	0	0	0	0	0	10
Lice Infestation
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	7 / 37 (18.92%)	10 / 39 (25.64%)	8 / 38 (21.05%)	0 / 13 (0.00%)	1 / 18 (5.56%)	4 / 23 (17.39%)	1 / 11 (9.09%)	5 / 27 (18.52%)	3 / 13 (23.08%)	25 / 87 (28.74%)
occurrences all number	9	11	10	0	1	4	1	5	3	36
Oral Herpes
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 13 (0.00%)	2 / 87 (2.30%)
occurrences all number	1	0	1	0	0	0	0	2	0	2
Pharyngitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	6 / 87 (6.90%)
occurrences all number	1	0	0	0	0	0	0	1	0	8
Pharyngitis Streptococcal
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 38 (2.63%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0
Rhinitis
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	3 / 38 (7.89%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)
occurrences all number	1	1	3	0	0	0	0	0	0	3
Upper Respiratory Tract Infection
subjects affected / exposed	6 / 37 (16.22%)	4 / 39 (10.26%)	2 / 38 (5.26%)	0 / 13 (0.00%)	2 / 18 (11.11%)	1 / 23 (4.35%)	0 / 11 (0.00%)	3 / 27 (11.11%)	0 / 13 (0.00%)	13 / 87 (14.94%)
occurrences all number	8	4	2	0	3	1	0	3	0	17
Urinary Tract Infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 27 (3.70%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	0	0	1	0	0	0	1	0	1
Varicella
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 27 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	1 / 38 (2.63%)	1 / 13 (7.69%)	0 / 18 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 27 (7.41%)	0 / 13 (0.00%)	2 / 87 (2.30%)
occurrences all number	1	1	1	1	0	0	0	3	0	3
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	0 / 38 (0.00%)	0 / 13 (0.00%)	0 / 18 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 27 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)
occurrences all number	1	1	0	0	0	0	1	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 Oct 2008

● added explanation for even-week dosing for Period D. ● updated adalimumab worldwide approval status for Rheumatoid Arthritis. ● updated Overall Study Design and Plan: minimum screening period changed from 48 to 72 hours, added information for the non-investigational medicinal product folic acid, added that subjects must complete all 16 weeks of treatment in Period C in order to be eligible to enter Period D. ● Study activities updated to remove the Family Dermatology Quality of Life Index (FDLQI), added the Children's Depression Index:Short (CDI:S) at Week 4A and 8A visits and removed all patient reported outcomes (PROs) from Week 11A visit, general labs and urinalysis were added at Weeks 0D and 52D; pharmacokinetic (PK)/Anti-adalimumab antibody (AAA) sample collection was added at Week 8D. ● Study procedures updated: language added regarding tuberculosis screening, lab analyses, FDLQI removed, CDLQI cartoon version removed, PedsQL parent proxy report for children ages 5-7 removed, information added for folic acid. ● Drug Concentration Measurements: removed sample collection at Week 16C and added sample collection at Week 8D. ● Secondary Variable, Ranked – Removed FDLQI ● Treatments Administered: Information for MTX was added, adalimumab dosing schedules for Periods A, C, and D were added and Information for folic acid was added.

15 Mar 2011

● Update the date related to the number of countries that adalimumab has been approved ● Add information on the maximum time subject would be participating in the study ● Added Differences Statement. ● Update inclusion criterion number 10 to include the QuantiFERON-TB Gold or equivalent test. ● Add new inclusion criterion number 16 regarding updated immunization schedule. ● Add wording on clinically significant abnormal screening laboratory results to exclusion criterion number 20. ● Provide new information on Hepatitis B testing for exclusion criterion number 14. ● Add new exclusion criterion number 23 regarding viral infections, and to incorporate adalimumab 0.8 mg/kg protocol wording. ● Add new exclusion criterion number 24 related to GFR. ● Add new exclusion criterion number 25 related to Hepatitis C. ● Add additional prohibited medications. ● Add general labs (hematology and chemistry) to the Week 8A visit Study Activities (Period A). ● Add additional time point for assessment of hs-CRP to Study Activities (Period D). ● Update chest x-ray and TB screening sections to include new information on QuantiFERON-TB Gold or equivalent test and to add content to include new adalimumab protocol standard wording. Add clarification that subjects enrolled under TB prophylaxis must continue the prophylaxis until entire course was completed. ● Add instruction for measurement of waist circumference at level of umbilicus for metabolic syndrome screening and reference to WHO Child Growth Charts. ● Add instructions on which version of PedsQL to complete as child ages during study. ● Add guidance on scheduling annual TB testing.

18 Jul 2013

● Updated Adalimumab Overview to reflect current information, as provided in the updated Investigator's Brochure version 19. ● Added Safety Information: section added to include new safety monitoring information. ● Updated Prior and Concomitant Therapy: added collection requirements for events of malignancy in patients 30 years of age or younger. ● Updated Prohibited Medications with newly available biologic therapies that are prohibited while in the study. ● Updated the following sections to comply with the Humira® standard protocol language in compliance with Investigator's Brochure version 19 (dated May 2013) and AbbVie policies and procedures: - Discontinuation of Individual Subjects: added that noncompliance with TB prophylaxis was grounds for discontinuation; removed the language regarding inclusion/exclusion criteria where safety was involved, as violations of inclusion and/or exclusion criteria are not necessarily grounds for discontinuation and are handled by the study designated physician; for protocol consistency changed medical monitor to study designated physician. - Drug Accountability: differentiated between the refrigerated and nonrefrigerated study drug; clarification made to differentiated drug dispensing depot from drug destruction depot. - Protocol Deviations: statement added that AbbVie does not grant waivers or allow any known or prospective protocol deviations. ● Adverse Event Reporting: added new requirements for reporting any serious adverse event or nonserious event of malignancy in patients 30 years of age or younger.

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

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sun Apr 28 21:26:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands