A Study of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Plaque Psoriasis Naive to Systemic Treatment

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02634801
• Collaborator: (none)
• Enrollment: 162
• Locations: 21
• Arms: 3
• Actual Duration (Months): 21.8
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy of ixekizumab compared to fumaric acid esters (FAE) and methotrexate (MTX) in participants with moderate-to-severe plaque psoriasis who are naive to systemic treatment.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Drug: Fumaric Acid Esters; Drug: Methotrexate; Drug: Ixekizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 24-Week Multicenter, Randomized, Open-Label, Parallel-Group Study Comparing the Efficacy and Safety of Ixekizumab to Fumaric Acid Esters and Methotrexate in Patients With Moderate-to-Severe Plaque Psoriasis Who Are Naive to Systemic Treatment With an Extension Period
• Actual Study Start Date: Jan 20, 2016
• Actual Primary Completion Date: Nov 29, 2016
• Actual Study Completion Date: Nov 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab 160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Drug: Ixekizumab; Administered SC; Other Names: LY2439821
Active Comparator: Fumaric Acid Esters Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	Drug: Fumaric Acid Esters; Administered orally; Drug: Ixekizumab; Administered SC; Other Names: LY2439821
Active Comparator: Methotrexate 7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	Drug: Methotrexate; Administered orally; Drug: Ixekizumab; Administered SC; Other Names: LY2439821

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) at Week 24 [Week 24]

   The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).

Secondary Outcome Measures

1. Percentage of Participants With a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) From Baseline [Week 24]

   The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).

2. Percentage of Participants With a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) From Baseline [Week 24]

   The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).

3. Change From Baseline in PASI Total Score [Baseline, Week 24]

   The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). LS mean change from baseline in PASI was calculated using Analysis of Covariance (ANCOVA) with modified Baseline- Observation- Carried Forward (mBOCF) and with terms for baseline and treatment.

4. Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) and ≥2 Point Improvement From Baseline Among Those With sPGA Score ≥3 at Baseline [Week 24]

   The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.

5. Percentage of Participants Achieving DLQI (0,1) [Week 24]

   The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant.

6. Change From Baseline on Dermatology Life Quality Index (DLQI) Total Score [Baseline, Week 24]

   The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant. LS mean change from baseline in DLQI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

7. Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis [Baseline, Week 24]

   The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean change from baseline in BSA was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

8. Change From Baseline in Palmoplantar Psoriasis Severity Index (PPASI) Total Score [Baseline, Week 24]

   The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean change from baseline in PPASI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

9. Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score [Baseline, Week 24]

   The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS mean change from baseline in PSSI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

10. Patient Benefit Index (PBI) Overall Benefit Score [Week 24]

    The PBI assessment consists of 2 steps: before treatment, every patient defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire [PNQ]). After treatment, the patient rates the degree of benefits achieved (Patient Benefits Questionnaire [PBQ]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "did not apply to me" (5) and missing. For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score. LS mean was calculated using ANCOVA with LOCF and with a term for treatment.

11. Change From Baseline on Itch Numeric Rating Scale (NRS) Score [Baseline, Week 24]

    The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

12. Change From Baseline on the Skin Pain Visual Analog Scale (VAS) [Baseline, Week 24]

    The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as severe as you can imagine). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

13. Change From Baseline on Quick Inventory of Depressive Symptomatology-Self Report (16 Items) (QIDS-SR16) [Baseline, Week 24]

    QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

14. Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) [Baseline, Week 24]

    The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

15. Change From Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Scores [Baseline, Week 24]

    The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

16. Change From Baseline on Patient's Global Assessment (PatGA) of Disease Severity [Baseline, Week 24]

    The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

17. Change From Baseline on the Psoriasis Skin Appearance Bothersomeness (PSAB) Total Score [Baseline, Week 24]

    PSAB measure is a 3-item scale designed to measure the degree of bothersomeness of skin appearance due to Ps in participants with Ps. Participants are asked to indicate on 3 numeric rating scales (NRS) from 0 (not at all bothered) to 10 (extremely bothered) how bothered they are by any redness or discoloration, thickness, and scaling or flaking on their skin due to Ps. The scores from the 3 NRS items are summed for a total score ranging from 0 to 30, where 0 indicating no bothersomeness and 30 indicating greater bothersomeness. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

18. Change From Baseline on the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN) Total Score [Baseline, Week 24]

    NAPPA is a clinical and participant-reported outcomes tool, and consists of 3 components: a questionnaire assessing nail-specific quality of life NAPPA-QoL (Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life), a 2-part questionnaire assessing participant relevant needs and treatment benefits NAPPA-PBI (Nail Assessment in Psoriasis and Psoriatic Arthritis - Patient Benefit Index), and a clinical assessment of objective finger nail psoriasis severity NAPPA-CLIN. Sum of all assessed finger and toes ranging between 0 (no involvement) to 16 (worst involvement). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

19. Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D) + Bolt On UK Population-based Index Score [Baseline, Week 24]

    The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a United Kingdom (UK) Population value set to each of the levels in each dimension. This produced participant-level index scores between -0.594 and 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

20. Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Psoriasis (PSO) Index Score [Baseline, Week 24]

    The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The Bolt On PSO is an addition to the EQ-5D-5L that consists of 2 dimensions specific to psoriatic disease: 6) skin irritation (itching) and 7) self-confidence. Index scores for the Bolt On PSO range from 0.0042 to 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

21. Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Visual Analog Scale Score [Baseline, Week 24]

    The EQ-5D 5L is a standardized measure of health status that includes a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health imaginable)- to 100 (best health imaginable)-millimeter (mm) Visual Analog Scale (VAS). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

22. Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Absenteeism Score [Baseline, Week 24]

    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

23. Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Presenteeism Score [Baseline, Week 24]

    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

24. Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Impairment in Activities Performed Outside of Work [Baseline, Week 24]

    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

25. Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Overall Work Impairment Score [Baseline, Week 24]

    The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.

26. Percentage of Participants With Positive Responses to Neck/Face Psoriasis Question [Week 24]

    Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. Does the participant currently have visible psoriasis on face/neck? (Yes/No) Does the participant currently have psoriasis on the genital area? (Yes/No)

27. Percentage of Participants Positive Responses to Genital Psoriasis Question [Week 24]

    Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. Does the patient currently have visible psoriasis on face/neck? (Yes/No) Does the patient currently have psoriasis on the genital area? (Yes/No) The genital area includes the labia majora (hair-bearing), labia minora modified mucus membrane, and perineum in female patients; and the penis glans, penis - shaft, and scrotum in male patients.

28. Mean Adherence on Medication and Satisfaction With Therapy (STAQ) [Week 24]

    Systemic Therapy Adherence Questionnaire (STAQ) is a 38 item questionnaire that was developed by shortening and adapting the Topical Treatment Adherence Questionnaire (TTAQ) for administration to participants under systemic therapy. The following STAQ items are of special interest for this study. STAQ item 13 (The treatment does not affect my sex life) STAQ item 16 (I am enjoying life again as a result of the treatment) STAQ item 20 (The side effects of the treatment were acceptable) STAQ item 31 (I am satisfied with the efficacy of the treatment) STAQ item 32 (I am satisfied with the tolerability of the treatment) STAQ item 35 (The positive aspects of the treatment outweigh the negative ones). The STAQ items are on a 4-point Likert scale with scores between 0 (strong disagreement) and 3 (strong agreement). LS mean was calculated using ANCOVA with term for treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Present with moderate-to-severe chronic plaque psoriasis based on a diagnosis of chronic psoriasis for at least 6 months before baseline.

• Participants who are candidates for systemic therapy and who are naive to systemic treatment for psoriasis.

• Have a (PASI score >10 or BSA >10) and DLQI >10 at screening and at baseline.

Exclusion Criteria:

• Have predominant pattern of pustular, erythrodermic, and/or guttate forms of psoriasis.

• Have received systemic nonbiologic psoriasis therapy.

• Have prior, concurrent, or recent use of ixekizumab or any other biological psoriasis therapy.

• Have any condition or contraindication as addressed in the local labeling for MTX or FAE.

• Presence of significant uncontrolled cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disorders or abnormal laboratory values at screening.

• Have severe gastrointestinal disease, oral ulcer, or known, active gastrointestinal ulcer.

• Have had a serious infection or are immunocompromised.

• At screening, participants with significant, present, or early liver disease, e.g., explained by alcohol consumption or hepatic insufficiency.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Augsburg		Germany	86179
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	10783
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bochum		Germany	44803
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bonn		Germany	53105
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Buxtehude		Germany	21614
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dresden		Germany	01307
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Erlangen		Germany	91054
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Essen		Germany	45122
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Frankfurt		Germany	60590
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Friedrichshafen		Germany	88045
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gelsenkirchen		Germany	45883
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	20354
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hanau		Germany	63450
14	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Kiel		Germany	24105
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lübeck		Germany	23538
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mannheim		Germany	68167
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Münster		Germany	48149
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Selters		Germany	56242
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stuttgart		Germany	70178
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tübingen		Germany	72076
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ulm		Germany	89081

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02634801
• Other Study ID Numbers: 16190; I1F-EW-RHBZ; 2015-002649-69
• First Posted: Dec 18, 2015
• Last Update Posted: Oct 9, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Eli Lilly and Company: Fumaderm
• Additional relevant MeSH terms: Psoriasis; Methotrexate; Ixekizumab

Study Results

Participant Flow

Recruitment Details	Treatment Period (Weeks 0 to 24), Extension Period (Weeks 24 to 36) followed by post-treatment follow-up period occurring from last treatment visit (week 36), or Early Termination Visit (ETV) up to a minimum of 12 weeks following that visit.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg Fumaric Acid Esters (FAE) given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg Methotrexate (MTX) given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Period Title: Treatment Period (Weeks 0 to 24)
STARTED	54	54	54
Received at Least 1 Dose of Study Drug	54	52	52
COMPLETED	50	23	49
NOT COMPLETED	4	31	5
Period Title: Treatment Period (Weeks 0 to 24)
STARTED	48	19	31
COMPLETED	45	18	29
NOT COMPLETED	3	1	2
Period Title: Treatment Period (Weeks 0 to 24)
STARTED	41	26	46
COMPLETED	36	18	38
NOT COMPLETED	5	8	8

Baseline Characteristics

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate	Total
Arm/Group Description	160 mg ixekizumab given as two SC injection followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	Total of all reporting groups
Overall Participants	54	54	54	162
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.3 (13.84)	43.1 (14.16)	38.7 (12.90)	42.1 (13.77)
Sex: Female, Male (Count of Participants)
Female	12 22.2%	11 20.4%	18 33.3%	41 25.3%
Male	42 77.8%	43 79.6%	36 66.7%	121 74.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 1.9%	0 0%	3 5.6%	4 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	43 79.6%	44 81.5%	42 77.8%	129 79.6%
More than one race	10 18.5%	10 18.5%	9 16.7%	29 17.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Germany	54 100%	54 100%	54 100%	162 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) at Week 24
Description	The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who had a post-baseline measurement for PASI 75. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	54	54
Number [Percentage of Participants]	90.7 168%	22.2 41.1%	70.4 130.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Fumaric Acid Esters
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	4.08
	Confidence Interval	(2-Sided) 95%; 2.46 to 6.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab, Methotrexate
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 1.06 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) From Baseline
Description	The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who had a post-baseline measurement for PASI 90. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	54	54
Number [Percentage of Participants]	79.6 147.4%	9.3 17.2%	38.9 72%

3. Secondary Outcome

Title	Percentage of Participants With a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) From Baseline
Description	The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who had a post-baseline measurement for PASI 100. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	54	54
Number [Percentage of Participants]	40.7 75.4%	3.7 6.9%	13.0 24.1%

4. Secondary Outcome

Title	Change From Baseline in PASI Total Score
Description	The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). LS mean change from baseline in PASI was calculated using Analysis of Covariance (ANCOVA) with modified Baseline- Observation- Carried Forward (mBOCF) and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PASI. mBOCF: Participants who discontinued treatment due to Adverse Event (AE) were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	50	52
Least Squares Mean (95% Confidence Interval) [units on a scale]	-16.68	-4.93	-14.61

5. Secondary Outcome

Title	Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) and ≥2 Point Improvement From Baseline Among Those With sPGA Score ≥3 at Baseline
Description	The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline sPGA >=3 & received at least 1 dose of study drug and had a post-baseline measurement for sPGA. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	53	52
Number [Percentage of Participants]	86.5 160.2%	13.2 24.4%	51.9 96.1%

6. Secondary Outcome

Title	Percentage of Participants Achieving DLQI (0,1)
Description	The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who had a post-baseline measurement for DLQI. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	54	54
Number [Percentage of Participants]	63.0 116.7%	14.8 27.4%	37.0 68.5%

7. Secondary Outcome

Title	Change From Baseline on Dermatology Life Quality Index (DLQI) Total Score
Description	The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and unanswered ("not relevant") responses scored as "0." Totals range from 0 to 30 (less to more impairment), and a 5-point change from baseline is considered clinically relevant. LS mean change from baseline in DLQI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for DLQI. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	49	49
Least Squares Mean (95% Confidence Interval) [units on a scale]	-13.08	-5.37	-12.81

8. Secondary Outcome

Title	Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis
Description	The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean change from baseline in BSA was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for BSA. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	50	52
Least Squares Mean (95% Confidence Interval) [% Body Surface Affected]	-20.64	-5.26	-18.46

9. Secondary Outcome

Title	Change From Baseline in Palmoplantar Psoriasis Severity Index (PPASI) Total Score
Description	The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean change from baseline in PPASI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PPASI. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	12	14	9
Least Squares Mean (95% Confidence Interval) [units on a scale]	-7.23	-2.45	-3.77

10. Secondary Outcome

Title	Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score
Description	The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS mean change from baseline in PSSI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for Psoriasis Scalp. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	40	39	40
Least Squares Mean (95% Confidence Interval) [units on a scale]	-20.85	-6.76	-18.56

11. Secondary Outcome

Title	Patient Benefit Index (PBI) Overall Benefit Score
Description	The PBI assessment consists of 2 steps: before treatment, every patient defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire [PNQ]). After treatment, the patient rates the degree of benefits achieved (Patient Benefits Questionnaire [PBQ]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "did not apply to me" (5) and missing. For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score. LS mean was calculated using ANCOVA with LOCF and with a term for treatment.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a baseline PBI questionnaire such that postbaseline PBI assessments can be valid (nonmissing).

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	43	41	50
Least Squares Mean (95% Confidence Interval) [units on a scale]	3.42	2.33	2.66

12. Secondary Outcome

Title	Change From Baseline on Itch Numeric Rating Scale (NRS) Score
Description	The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for Itch NRS score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	53	50	52
Least Squares Mean (95% Confidence Interval) [units on a scale]	-5.25	-1.50	-4.40

13. Secondary Outcome

Title	Change From Baseline on the Skin Pain Visual Analog Scale (VAS)
Description	The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as severe as you can imagine). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for skin pain VAS. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	53	50	52
Least Squares Mean (95% Confidence Interval) [Millimeter (mm)]	-33.83	-7.20	-28.29

14. Secondary Outcome

Title	Change From Baseline on Quick Inventory of Depressive Symptomatology-Self Report (16 Items) (QIDS-SR16)
Description	QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for QIDS-SR16. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	51	49	50
Least Squares Mean (95% Confidence Interval) [units on a scale]	-2.16	-1.01	-2.50

15. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS)
Description	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for SF36 PCS score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	50	48	49
Least Squares Mean (95% Confidence Interval) [units on a scale]	4.45	0.57	4.01

16. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Scores
Description	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for SF36 MCS score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	50	48	49
Least Squares Mean (95% Confidence Interval) [units on a scale]	7.13	3.39	6.99

17. Secondary Outcome

Title	Change From Baseline on Patient's Global Assessment (PatGA) of Disease Severity
Description	The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PatGA. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	54	50	50
Least Squares Mean (95% Confidence Interval) [units on a scale]	-3.12	-0.87	-2.39

18. Secondary Outcome

Title	Change From Baseline on the Psoriasis Skin Appearance Bothersomeness (PSAB) Total Score
Description	PSAB measure is a 3-item scale designed to measure the degree of bothersomeness of skin appearance due to Ps in participants with Ps. Participants are asked to indicate on 3 numeric rating scales (NRS) from 0 (not at all bothered) to 10 (extremely bothered) how bothered they are by any redness or discoloration, thickness, and scaling or flaking on their skin due to Ps. The scores from the 3 NRS items are summed for a total score ranging from 0 to 30, where 0 indicating no bothersomeness and 30 indicating greater bothersomeness. LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for PSAB. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	47	48
Least Squares Mean (95% Confidence Interval) [units on a scale]	-19.87	-5.18	-15.05

19. Secondary Outcome

Title	Change From Baseline on the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN) Total Score
Description	NAPPA is a clinical and participant-reported outcomes tool, and consists of 3 components: a questionnaire assessing nail-specific quality of life NAPPA-QoL (Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life), a 2-part questionnaire assessing participant relevant needs and treatment benefits NAPPA-PBI (Nail Assessment in Psoriasis and Psoriatic Arthritis - Patient Benefit Index), and a clinical assessment of objective finger nail psoriasis severity NAPPA-CLIN. Sum of all assessed finger and toes ranging between 0 (no involvement) to 16 (worst involvement). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who had palmoplantar, scalp, or nail involvement at baseline. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	35	29	27
Least Squares Mean (95% Confidence Interval) [units on a scale]	-6.58	-0.14	-3.41

20. Secondary Outcome

Title	Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D) + Bolt On UK Population-based Index Score
Description	The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a United Kingdom (UK) Population value set to each of the levels in each dimension. This produced participant-level index scores between -0.594 and 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L Index.mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	47	50
Least Squares Mean (95% Confidence Interval) [units on a scale]	0.15	0.04	0.15

21. Secondary Outcome

Title	Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Psoriasis (PSO) Index Score
Description	The European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The Bolt On PSO is an addition to the EQ-5D-5L that consists of 2 dimensions specific to psoriatic disease: 6) skin irritation (itching) and 7) self-confidence. Index scores for the Bolt On PSO range from 0.0042 to 1.0 (worse to better health). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L "Bolt On" PSO-Index. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	46	50
Least Squares Mean (95% Confidence Interval) [units on a scale]	0.15	0.05	0.13

22. Secondary Outcome

Title	Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Visual Analog Scale Score
Description	The EQ-5D 5L is a standardized measure of health status that includes a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health imaginable)- to 100 (best health imaginable)-millimeter (mm) Visual Analog Scale (VAS). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for EQ-5D 5L + Bolt on VAS. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	52	48	50
Least Squares Mean (95% Confidence Interval) [Millimeter (mm)]	16.91	6.08	13.91

23. Secondary Outcome

Title	Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Absenteeism Score
Description	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO absenteeism score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	26	30	39
Least Squares Mean (95% Confidence Interval) [units on a scale]	3.08	-1.26	0.06

24. Secondary Outcome

Title	Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Presenteeism Score
Description	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO Presenteeism score. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	29	32	39
Least Squares Mean (95% Confidence Interval) [units on a scale]	-22.70	-5.29	-20.32

25. Secondary Outcome

Title	Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Impairment in Activities Performed Outside of Work
Description	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	53	50	48
Least Squares Mean (95% Confidence Interval) [units on a scale]	-28.23	-3.45	-23.57

26. Secondary Outcome

Title	Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Overall Work Impairment Score
Description	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment). LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for WPAI-PSO. mBOCF: Participants who discontinued treatment due to AE were imputed by their baseline observation, Participants who discontinued due to other reasons were imputed by their last observation.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	25	30	38
Least Squares Mean (95% Confidence Interval) [units on a scale]	-18.20	-6.20	-19.80

27. Secondary Outcome

Title	Percentage of Participants With Positive Responses to Neck/Face Psoriasis Question
Description	Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. Does the participant currently have visible psoriasis on face/neck? (Yes/No) Does the participant currently have psoriasis on the genital area? (Yes/No)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for binary questions. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	33	34	36
Number [Percentage of Participants]	81.8 151.5%	26.5 49.1%	66.7 123.5%

28. Secondary Outcome

Title	Percentage of Participants Positive Responses to Genital Psoriasis Question
Description	Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life. Following set of binary questions were asked to check the satisfaction of participants. Does the patient currently have visible psoriasis on face/neck? (Yes/No) Does the patient currently have psoriasis on the genital area? (Yes/No) The genital area includes the labia majora (hair-bearing), labia minora modified mucus membrane, and perineum in female patients; and the penis glans, penis - shaft, and scrotum in male patients.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had baseline and a post-baseline measurement for binary questions. Participants who did not meet the clinical response criteria or had missing data were considered non-responders for Non-Responder Imputation (NRI) analysis.

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	20	24	24
Number [Percentage of participants]	85.0 157.4%	29.2 54.1%	75.0 138.9%

29. Secondary Outcome

Title	Mean Adherence on Medication and Satisfaction With Therapy (STAQ)
Description	Systemic Therapy Adherence Questionnaire (STAQ) is a 38 item questionnaire that was developed by shortening and adapting the Topical Treatment Adherence Questionnaire (TTAQ) for administration to participants under systemic therapy. The following STAQ items are of special interest for this study. STAQ item 13 (The treatment does not affect my sex life) STAQ item 16 (I am enjoying life again as a result of the treatment) STAQ item 20 (The side effects of the treatment were acceptable) STAQ item 31 (I am satisfied with the efficacy of the treatment) STAQ item 32 (I am satisfied with the tolerability of the treatment) STAQ item 35 (The positive aspects of the treatment outweigh the negative ones). The STAQ items are on a 4-point Likert scale with scores between 0 (strong disagreement) and 3 (strong agreement). LS mean was calculated using ANCOVA with term for treatment.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a post-baseline measurement for Systemic Therapy Adherence Questionnaire (STAQ).

Arm/Group Title	Ixekizumab	Fumaric Acid Esters	Methotrexate
Arm/Group Description	160 mg ixekizumab given as two SC injections followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Measure Participants	49	22	48
STAQ item 13	2.84	2.75	2.78
STAQ item 16	2.82	2.00	2.43
STAQ item 20	2.76	2.00	2.42
STAQ item 31	2.88	2.09	2.29
STAQ item 32	2.86	1.95	2.50
STAQ item 35	2.80	2.14	2.53

Adverse Events

Time Frame	Up to 48 Weeks
Adverse Event Reporting Description	All the randomized participants who received at least one dose of the study drug.
Arm/Group Title	Ixekizumab-Treatment Period		Fumaric Acid Esters-Treatment Period		Methotrexate-Treatment Period		Ixekizumab-Extension Period		Fumaric Acid Esters-Extension Period		Methotrexate-Extension Period		Follow-up Period
Arm/Group Description	160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.		Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.		7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.		160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.		Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.		7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.		Participants were allowed to continue the treatment administered during the treatment and extension period.
All Cause Mortality
	Ixekizumab-Treatment Period		Fumaric Acid Esters-Treatment Period		Methotrexate-Treatment Period		Ixekizumab-Extension Period		Fumaric Acid Esters-Extension Period		Methotrexate-Extension Period		Follow-up Period
	Affected / at Risk (%)	# Events	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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixekizumab-Treatment Period		Fumaric Acid Esters-Treatment Period		Methotrexate-Treatment Period		Ixekizumab-Extension Period		Fumaric Acid Esters-Extension Period		Methotrexate-Extension Period		Follow-up Period
	Affected / at Risk (%)	# Events	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	1/54 (1.9%)		3/52 (5.8%)		1/52 (1.9%)		3/48 (6.3%)		1/19 (5.3%)		4/31 (12.9%)		4/113 (3.5%)
Blood and lymphatic system disorders
Lymphadenopathy	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	1/113 (0.9%)	1
Cardiac disorders
Atrioventricular block complete	1/54 (1.9%)	1	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/54 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Colitis	0/54 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Gastritis erosive	0/54 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Hepatobiliary disorders
Hepatic cirrhosis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	1/113 (0.9%)	1
Infections and infestations
Erysipelas	0/54 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Gastroenteritis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	1/113 (0.9%)	1
Infected dermal cyst	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/54 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0	1/48 (2.1%)	1	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Osteoarthritis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	1/31 (3.2%)	1	0/113 (0%)	0
Invasive lobular breast carcinoma	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	1/48 (2.1%)	1	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Pancreatic neuroendocrine tumour	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	1/48 (2.1%)	1	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Nervous system disorders
Sciatica	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	1/113 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	1/31 (3.2%)	1	0/113 (0%)	0
Other (Not Including Serious) Adverse Events
	Ixekizumab-Treatment Period		Fumaric Acid Esters-Treatment Period		Methotrexate-Treatment Period		Ixekizumab-Extension Period		Fumaric Acid Esters-Extension Period		Methotrexate-Extension Period		Follow-up Period
	Affected / at Risk (%)	# Events	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	37/54 (68.5%)		39/52 (75%)		38/52 (73.1%)		24/48 (50%)		15/19 (78.9%)		18/31 (58.1%)		0/113 (0%)
Blood and lymphatic system disorders
Lymphopenia	0/54 (0%)	0	5/52 (9.6%)	5	2/52 (3.8%)	2	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Ear and labyrinth disorders
Middle ear inflammation	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Vertigo	2/54 (3.7%)	2	3/52 (5.8%)	3	3/52 (5.8%)	5	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	2/54 (3.7%)	2	19/52 (36.5%)	26	6/52 (11.5%)	6	1/48 (2.1%)	1	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Diarrhoea	1/54 (1.9%)	1	24/52 (46.2%)	29	6/52 (11.5%)	6	1/48 (2.1%)	1	1/19 (5.3%)	1	1/31 (3.2%)	1	0/113 (0%)	0
Dyspepsia	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Flatulence	0/54 (0%)	0	3/52 (5.8%)	3	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Nausea	1/54 (1.9%)	1	3/52 (5.8%)	4	5/52 (9.6%)	14	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Oral mucosal eruption	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Vomiting	0/54 (0%)	0	3/52 (5.8%)	4	0/52 (0%)	0	1/48 (2.1%)	1	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
General disorders
Fatigue	4/54 (7.4%)	4	3/52 (5.8%)	3	8/52 (15.4%)	14	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Injection site erythema	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	2/19 (10.5%)	10	3/31 (9.7%)	13	0/113 (0%)	0
Injection site pruritus	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	3	1/31 (3.2%)	1	0/113 (0%)	0
Injection site reaction	7/54 (13%)	23	0/52 (0%)	0	0/52 (0%)	0	1/48 (2.1%)	9	3/19 (15.8%)	6	6/31 (19.4%)	31	0/113 (0%)	0
Injection site swelling	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	2/19 (10.5%)	10	3/31 (9.7%)	9	0/113 (0%)	0
Infections and infestations
Bronchitis	1/54 (1.9%)	1	1/52 (1.9%)	1	1/52 (1.9%)	1	2/48 (4.2%)	2	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Gastroenteritis	1/54 (1.9%)	1	1/52 (1.9%)	1	0/52 (0%)	0	2/48 (4.2%)	2	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Impetigo	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Nasopharyngitis	20/54 (37%)	23	9/52 (17.3%)	13	18/52 (34.6%)	21	18/48 (37.5%)	25	6/19 (31.6%)	7	10/31 (32.3%)	15	0/113 (0%)	0
Sinusitis	0/54 (0%)	0	1/52 (1.9%)	1	1/52 (1.9%)	1	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Tinea pedis	2/54 (3.7%)	2	0/52 (0%)	0	1/52 (1.9%)	1	1/48 (2.1%)	1	2/19 (10.5%)	2	0/31 (0%)	0	0/113 (0%)	0
Tooth infection	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/54 (0%)	0	0/52 (0%)	0	3/52 (5.8%)	3	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Investigations
Aspartate aminotransferase increased	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	1/31 (3.2%)	1	0/113 (0%)	0
Gamma-glutamyltransferase increased	0/54 (0%)	0	3/52 (5.8%)	3	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Weight increased	1/54 (1.9%)	1	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Metabolism and nutrition disorders
Hyperlipidaemia	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/54 (3.7%)	2	0/52 (0%)	0	4/52 (7.7%)	6	1/48 (2.1%)	1	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Back pain	1/54 (1.9%)	1	2/52 (3.8%)	2	5/52 (9.6%)	5	3/48 (6.3%)	3	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Bursitis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Musculoskeletal pain	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Myalgia	0/54 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1	0/48 (0%)	0	2/19 (10.5%)	4	0/31 (0%)	0	0/113 (0%)	0
Pain in extremity	1/54 (1.9%)	1	1/52 (1.9%)	1	0/52 (0%)	0	1/48 (2.1%)	1	1/19 (5.3%)	1	1/31 (3.2%)	1	0/113 (0%)	0
Nervous system disorders
Dizziness	2/54 (3.7%)	2	0/52 (0%)	0	1/52 (1.9%)	1	1/48 (2.1%)	1	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Headache	7/54 (13%)	7	4/52 (7.7%)	4	9/52 (17.3%)	12	1/48 (2.1%)	1	1/19 (5.3%)	1	2/31 (6.5%)	2	0/113 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Cough	1/54 (1.9%)	1	2/52 (3.8%)	2	1/52 (1.9%)	1	1/48 (2.1%)	1	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Oropharyngeal pain	3/54 (5.6%)	3	1/52 (1.9%)	1	1/52 (1.9%)	1	1/48 (2.1%)	1	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/54 (3.7%)	2	0/52 (0%)	0	1/52 (1.9%)	1	0/48 (0%)	0	0/19 (0%)	0	2/31 (6.5%)	2	0/113 (0%)	0
Dermatitis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Eczema	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	2/48 (4.2%)	4	2/19 (10.5%)	2	2/31 (6.5%)	2	0/113 (0%)	0
Ingrowing nail	0/54 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Nail psoriasis	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Night sweats	0/54 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Xanthelasma	0/54 (0%)	0	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0
Vascular disorders
Flushing	0/54 (0%)	0	13/52 (25%)	19	0/52 (0%)	0	0/48 (0%)	0	0/19 (0%)	0	0/31 (0%)	0	0/113 (0%)	0
Haematoma	1/54 (1.9%)	1	0/52 (0%)	0	0/52 (0%)	0	0/48 (0%)	0	1/19 (5.3%)	1	0/31 (0%)	0	0/113 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.