BI 655066/ABBV-066 (Risankizumab) Compared to Active Comparator (Adalimumab) in Patients With Moderate to Severe Chronic Plaque Psoriasis

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02694523
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 684
• Arms: 2
• Actual Duration (Months): 17

Study Details

Study Description

Brief Summary

This is a randomized double blind, double dummy, active comparator controlled, parallel design study that is performed to assess the safety and efficacy of BI 655066/ABBV-066 (risankizumab) compared to adalimumab to support registration for the treatment of moderate to severe chronic plaque psoriasis in adult patients.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: risankizumab; Biological: adalimumab; Drug: placebo for risankizumab; Biological: placebo for adalimumab	Phase 3

Detailed Description

This study consists of 2 parts (Part A and Part B).

Part A:

• Participants were randomized to receive either risankizumab or adalimumab.

Part B:

• Participants who received risankizumab in Part A continued to receive risankizumab in Part B

• Adalimumab nonresponders (<PASI 50 at Week 16) switched to risankizumab in Part B;

• Adalimumab responders (PASI 90 at Week 16) continued to received adalimumab in Part B;

• Adalimumab inadequate responders (PASI 50 to <PASI 90) were rerandomized to receive either risankizumab or adalimumab in Part B.

Study Design

• Study Type: Interventional
• Actual Enrollment: 684 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: BI 655066/ABBV-066 (Risankizumab) Versus Adalimumab in a Randomized, Double Blind, Parallel Group Trial in Moderate to Severe Plaque Psoriasis to Assess Safety and Efficacy After 16 Weeks of Treatment and After Inadequate Adalimumab Treatment Response (IMMvent)
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Adalimumab (Part A) Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Biological: adalimumab; Adalimumab pre-filled syringe, administered by subcutaneous (SC) injection; Other Names: Humira ABT-D2E7 ; Drug: placebo for risankizumab; Placebo risankizumab administered by subcutaneous (SC) injection
Experimental: Risankizumab (Part A) Participants randomized to receive risankizumab at Weeks 0 and 4 (Part A).	Drug: risankizumab; Risankizumab administered by subcutaneous (SC) injection; Other Names: BI 655066 ABBV-066 SKYRIZI ; Biological: placebo for adalimumab; Placebo for adalimumab pre-filled syringe, administered by subcutaneous (SC) injection

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 (Part A) [Week 16]

   PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. Nonresponder imputation (NRI) was used for missing data.

2. Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 (Part A) [Week 16]

   The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.

3. Percentage of Participants Who Were Re-Randomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI90 at Week 44 (Part B) [Week 44]

   PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.

Secondary Outcome Measures

1. Percentage of Participants Achieving PASI75 at Week 16 (Part A) [Week 16]

   PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.

2. Percentage of Participants Achieving PASI100 at Week 16 (Part A) [Week 16]

   PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.

3. Percentage of Participants Who Were Rerandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI100 at Week 44 (Part B) [Week 44]

   PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.

4. Percentage of Participants Who Were ReRandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving sPGA Score of Clear at Week 44 (Part B) [Week 44]

   The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.

Other Outcome Measures

1. Percentage of Participants Who Were Rerandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving sPGA Score of Clear or Almost Clear at Week 44 (Part B) [Week 44]

   The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male or female patients. Women of childbearing potential* must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

*Women of childbearing potential are defined as:

• having experienced menarche and

• not postmenopausal (12 months with no menses without an alternative medical cause) and

• not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

• Age ≥ 18 years at screening

• Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before the first administration of study drug. Duration of diagnosis may be reported by the patient.

• Have stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis at both Screening and Baseline (Randomization):

• Have an involved body surface area (BSA) ≥ 10% and

• Have a Psoriasis Area and Severity Index (PASI) score ≥ 12 and

• Have a static Physician Global Assessment (sPGA) score of ≥ 3.

• Must be candidates for systemic therapy or phototherapy for psoriasis treatment, as assessed by the investigator

• Must be candidates for treatment with adalimumab (Humira®) according to local label as confirmed by the investigator.

• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

Exclusion criteria:

• Patients with

• non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)

• current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium)

• active ongoing inflammatory diseases other than psoriasis that might confound trial evaluations according to investigator's judgment

• Previous exposure to ABBV-066

• Previous exposure to adalimumab (Humira®)

• Currently enrolled in another investigational study or less than 30 days or more from screening since completing another investigational drug or device study.

• Use of any restricted medication or any drug considered likely to interfere with the safe conduct of the study.

• Major surgery performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g. hip replacement, removal aneurysm, stomach ligation).

• Known chronic or relevant acute infections, such as active tuberculosis (TB), human immunodeficiency virus (HIV) or viral hepatitis; QuantiFERON® TB test or purified protein derivative (PPD) skin test will be performed according to local labelling for Humira®. If the result is positive, patients may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active TB. If presence of latent TB is established, then treatment should have been initiated and maintained according to local country guidelines.

• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.

• Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and electrocardiogram [ECG]), or laboratory value at the Screening Visit outside the reference range that in the opinion of the investigator is clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data.

• History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial

• Previous enrolment in this trial

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie
• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Oct 17, 2016
• Statistical Analysis Plan - Sep 12, 2017

More Information

Additional Information:

• Related Info

Publications

• Reich K, Gooderham M, Thaçi D, Crowley JJ, Ryan C, Krueger JG, Tsai TF, Flack M, Gu Y, Williams DA, Thompson EHZ, Paul C. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019 Aug 17;394(10198):576-586. doi: 10.1016/S0140-6736(19)30952-3. Epub 2019 Jul 4. Erratum in: Lancet. 2019 Jul 16;:.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02694523
• Other Study ID Numbers: M16-010; 2015-003623-65; 1311.30
• First Posted: Feb 29, 2016
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie: Psoriasis; Skin Diseases; Skin Diseases, Papulosquamous; Adalimumab; Anti-Inflammatory Agents; ABBV-066; BI 655066; Risankizumab
• Additional relevant MeSH terms: Psoriasis; Adalimumab; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	A total of 684 subjects were enrolled; 79 subjects failed screening and are excluded from the analyses.

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)	Risankizumab/Risankizumab (Part B)	Adalimumab/Adalimumab (Part B)	Adalimumab/Risankizumab (Part B)	Adalimumab/Rerandomized to Adalimumab (Part B)	Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).	Participants randomized to receive double-blind (DB) risankizumab in Part A continued to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, and 28 (Part B).	Participants who were responders after receiving adalimumab in Part A continued to receive adalimumab 40 mg by subcutaneous (SC) injection every other week through Week 41 (Part B).	Participants who were nonresponders after receiving adalimumab in Part A switched to risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A and rerandomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A and rerandomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
Period Title: Part A
STARTED	304	301	0	0	0	0	0
COMPLETED	291	294	0	0	0	0	0
NOT COMPLETED	13	7	0	0	0	0	0
Period Title: Part A
STARTED	0	0	294	144	38	56	53
COMPLETED	0	0	274	140	34	51	51
NOT COMPLETED	0	0	20	4	4	5	2

Baseline Characteristics

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)	Total
Arm/Group Description	Participants randomized to receive double blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Weeks 0, 1, and every other week for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0, 4 (Part A).	Total of all reporting groups
Overall Participants	304	301	605
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.0 (13.09)	45.3 (13.79)	46.2 (13.46)
Sex: Female, Male (Count of Participants)
Female	92 30.3%	91 30.2%	183 30.2%
Male	212 69.7%	210 69.8%	422 69.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	59 19.4%	44 14.6%	103 17%
Not Hispanic or Latino	245 80.6%	257 85.4%	502 83%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 0.7%	2 0.3%
Asian	35 11.5%	41 13.6%	76 12.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 2%	11 3.7%	17 2.8%
White	263 86.5%	245 81.4%	508 84%
More than one race	0 0%	2 0.7%	2 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 (Part A)
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 (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. Nonresponder imputation (NRI) was used for missing data.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Intent-to-treat population in Part A (ITT_A): All subjects randomized at Baseline.

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).
Measure Participants	304	301
Number [percentage of participants]	47.4 15.6%	72.4 24.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to tumor necrosis factor (TNF) antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	24.9
	Confidence Interval	(2-Sided) 95%; 17.5 to 32.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Achieving Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 (Part A)
Description	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

ITT_A population.

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).
Measure Participants	304	301
Number [percentage of participants]	60.2 19.8%	83.7 27.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	23.3
	Confidence Interval	(2-Sided) 95%; 16.6 to 30.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Percentage of Participants Who Were Re-Randomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI90 at Week 44 (Part B)
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 (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.
Time Frame	Week 44

Outcome Measure Data

Analysis Population Description

Intent-to-treat population in Part B who were re-randomized (ITT_B_RR): All subjects who started with adalimumab at Baseline and were re-randomized at Week 16

Arm/Group Title	Adalimumab/Rerandomized to Adalimumab (Part B)	Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
Measure Participants	56	53
Number [percentage of participants]	21.4 7%	66.0 21.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	45.0
	Confidence Interval	(2-Sided) 95%; 28.9 to 61.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving PASI75 at Week 16 (Part A)
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 (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

ITT_A population

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).
Measure Participants	304	301
Number [percentage of participants]	71.7 23.6%	90.7 30.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	18.9
	Confidence Interval	(2-Sided) 95%; 13.0 to 24.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Achieving PASI100 at Week 16 (Part A)
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 (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

ITT_A population

Arm/Group Title	Adalimumab (Part A)	Risankizumab (Part A)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).	Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).
Measure Participants	304	301
Number [percentage of participants]	23.0 7.6%	39.9 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 9.5 to 23.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Who Were Rerandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving PASI100 at Week 44 (Part B)
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 (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.
Time Frame	Week 44

Outcome Measure Data

Analysis Population Description

ITT_B_RR population

Arm/Group Title	Adalimumab/Rerandomized to Adalimumab (Part B)	Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
Measure Participants	56	53
Number [percentage of participants]	7.1 2.3%	39.6 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 18.8 to 46.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants Who Were ReRandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving sPGA Score of Clear at Week 44 (Part B)
Description	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.
Time Frame	Week 44

Outcome Measure Data

Analysis Population Description

ITT_B_RR population

Arm/Group Title	Adalimumab/Rerandomized to Adalimumab (Part B)	Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
Measure Participants	56	53
Number [percentage of participants]	7.1 2.3%	39.6 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 18.8 to 46.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Other Pre-specified Outcome

Title	Percentage of Participants Who Were Rerandomized to Receive Either Adalimumab or Risankizumab in Part B Achieving sPGA Score of Clear or Almost Clear at Week 44 (Part B)
Description	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean ≥1.5, <2.5; Moderate (3) = mean ≥2.5, <3.5; and Severe (4) = mean ≥3.5. NRI was used for missing data.
Time Frame	Week 44

Outcome Measure Data

Analysis Population Description

ITT_B_RR population

Arm/Group Title	Adalimumab/Rerandomized to Adalimumab (Part B)	Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).	Participants who were inadequate responders after receiving adalimumab in Part A, and rerandomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
Measure Participants	56	53
Number [percentage of participants]	33.9 11.2%	73.6 24.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab (Part A), Risankizumab (Part A)
	Comments	P-value calculated according to the Cochran-Mantel-Haenszel test adjusted for baseline weight (≤100 kg vs >100 kg) and prior exposure to TNF antagonists (0 vs ≥1).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	difference in percentage of participants
	Estimated Value	38.9
	Confidence Interval	(2-Sided) 95%; 22.0 to 55.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 15 weeks after the last dose of study drug (up to 48 weeks).
Adverse Event Reporting Description	AEs in Part A are defined as events from the first dose of study drug in Part A until prior to the first dose in Part B (Week 16) or up to 15 weeks after the last dose of study drug if the participant discontinued in Part A; AEs in Part B are defined as events from the first dose of study drug in Part B (Week 16) until up to 15 weeks after the last dose of study drug.
Arm/Group Title	Adalimumab (Part A)		Risankizumab (Part A)		Risankizumab/Risankizumab (Part B)		Adalimumab/Risankizumab (Part B)		Adalimumab/Rerandomized to Adalimumab (Part B)		Adalimumab/Rerandomized to Risankizumab (Part B)
Arm/Group Description	Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A).		Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 4 (Part A).		Participants randomized to receive double-blind (DB) risankizumab in Part A continued to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, and 28 (Part B).		Participants who were nonresponders after receiving adalimumab in Part A switched to risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).		Participants who were inadequate responders after receiving adalimumab in Part A and re-randomized to continue to receive adalimumab 40 mg by subcutaneous (SC) injection every 2 weeks through Week 41 (Part B).		Participants who were inadequate responders after receiving adalimumab in Part A and re-randomized to receive risankizumab 150 mg by subcutaneous (SC) injection at Weeks 16, 20, and 32 (Part B).
All Cause Mortality
	Adalimumab (Part A)		Risankizumab (Part A)		Risankizumab/Risankizumab (Part B)		Adalimumab/Risankizumab (Part B)		Adalimumab/Rerandomized to Adalimumab (Part B)		Adalimumab/Rerandomized to Risankizumab (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/304 (0.7%)		1/301 (0.3%)		0/294 (0%)		0/38 (0%)		0/56 (0%)		0/53 (0%)
Serious Adverse Events
	Adalimumab (Part A)		Risankizumab (Part A)		Risankizumab/Risankizumab (Part B)		Adalimumab/Risankizumab (Part B)		Adalimumab/Rerandomized to Adalimumab (Part B)		Adalimumab/Rerandomized to Risankizumab (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/304 (3%)		10/301 (3.3%)		12/294 (4.1%)		4/38 (10.5%)		2/56 (3.6%)		3/53 (5.7%)
Blood and lymphatic system disorders
Lymphadenopathy mediastinal	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Cardiac failure congestive	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Coronary artery occlusion	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Myocardial infarction	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Palpitations	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	1/56 (1.8%)	1	0/53 (0%)	0
Congenital, familial and genetic disorders
Macrocornea	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Eye disorders
Macular hole	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Gastric perforation	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Gastritis	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Pancreatitis	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Hepatobiliary disorders
Cholelithiasis	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Liver injury	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Infections and infestations
Abdominal abscess	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Erysipelas	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	2/38 (5.3%)	2	0/56 (0%)	0	0/53 (0%)	0
Influenza	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	1/53 (1.9%)	1
Perirectal abscess	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Pneumonia	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Sepsis	1/304 (0.3%)	1	0/301 (0%)	0	1/294 (0.3%)	1	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Urinary tract infection	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	1/53 (1.9%)	1
Injury, poisoning and procedural complications
Fall	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Joint dislocation	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	1/53 (1.9%)	1
Radius fracture	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Respiratory fume inhalation disorder	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Upper limb fracture	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Investigations
Anticoagulation drug level above therapeutic	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Diabetes mellitus inadequate control	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	1/56 (1.8%)	1	0/53 (0%)	0
Diabetic ketoacidosis	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Musculoskeletal chest pain	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Gallbladder cancer	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Invasive lobular breast carcinoma	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Prostate cancer	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Nervous system disorders
Syncope	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Psychiatric disorders
Alcohol withdrawal syndrome	0/304 (0%)	0	0/301 (0%)	0	0/294 (0%)	0	1/38 (2.6%)	1	0/56 (0%)	0	0/53 (0%)	0
Anxiety	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Depression	0/304 (0%)	0	1/301 (0.3%)	1	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Suicide attempt	1/304 (0.3%)	1	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Reproductive system and breast disorders
Haemorrhagic ovarian cyst	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Respiratory failure	0/304 (0%)	0	1/301 (0.3%)	1	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Surgical and medical procedures
Abortion induced	0/304 (0%)	0	0/301 (0%)	0	1/294 (0.3%)	1	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Vascular disorders
Hypertensive crisis	1/304 (0.3%)	1	0/301 (0%)	0	0/294 (0%)	0	0/38 (0%)	0	0/56 (0%)	0	0/53 (0%)	0
Other (Not Including Serious) Adverse Events
	Adalimumab (Part A)		Risankizumab (Part A)		Risankizumab/Risankizumab (Part B)		Adalimumab/Risankizumab (Part B)		Adalimumab/Rerandomized to Adalimumab (Part B)		Adalimumab/Rerandomized to Risankizumab (Part B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/304 (23.4%)		76/301 (25.2%)		95/294 (32.3%)		16/38 (42.1%)		21/56 (37.5%)		24/53 (45.3%)
Infections and infestations
Bronchitis	3/304 (1%)	3	4/301 (1.3%)	4	7/294 (2.4%)	8	2/38 (5.3%)	2	3/56 (5.4%)	3	2/53 (3.8%)	2
Upper respiratory tract infection	12/304 (3.9%)	15	21/301 (7%)	26	34/294 (11.6%)	44	3/38 (7.9%)	5	5/56 (8.9%)	5	4/53 (7.5%)	6
Viral upper respiratory tract infection	24/304 (7.9%)	29	26/301 (8.6%)	31	39/294 (13.3%)	48	9/38 (23.7%)	14	7/56 (12.5%)	8	14/53 (26.4%)	19
Musculoskeletal and connective tissue disorders
Arthralgia	9/304 (3%)	12	11/301 (3.7%)	12	4/294 (1.4%)	4	0/38 (0%)	0	3/56 (5.4%)	5	2/53 (3.8%)	2
Back pain	6/304 (2%)	6	9/301 (3%)	9	6/294 (2%)	6	0/38 (0%)	0	3/56 (5.4%)	3	2/53 (3.8%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis	0/304 (0%)	0	0/301 (0%)	0	2/294 (0.7%)	2	2/38 (5.3%)	2	0/56 (0%)	0	0/53 (0%)	0
Nervous system disorders
Headache	20/304 (6.6%)	29	12/301 (4%)	13	6/294 (2%)	7	2/38 (5.3%)	2	3/56 (5.4%)	4	3/53 (5.7%)	3
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/304 (1%)	3	6/301 (2%)	6	3/294 (1%)	4	2/38 (5.3%)	2	1/56 (1.8%)	1	2/53 (3.8%)	2
Vascular disorders
Hypertension	8/304 (2.6%)	12	1/301 (0.3%)	1	9/294 (3.1%)	9	3/38 (7.9%)	3	1/56 (1.8%)	1	1/53 (1.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.