Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: Inclusion Criteria:

1. Subjects must give a written and signed informed consent.
2. Men or women at least 18 years old at the time of signing the ICF
3. Moderate to severe plaque psoriasis diagnosed at least 6 months before signing the informed consent form.
4. Patients received at least one course of phototherapy or systemic therapy for psoriasis or are candidates for such treatment according to the investigator.
5. Body surface area (BSA) affected by psoriasis of 10% or greater, the PASI score of 10 or greater, and the sPGA score of 3 or greater at screening.
6. Negative pregnancy urine test in female subjects (no test is required in women who are post-menopausal for at least 2 years and in surgically sterile women).
7. The patient must be able to follow the Protocol procedures (in the investigator's opinion).
8. Patients of childbearing potential and their partners with preserved reproductive function must implement reliable contraceptive methods starting from signing informed consent to 20 weeks after the last dose of the study therapy. This requirement does not apply to the patients after surgical sterilization and to females who are post-menopausal for 2 years or longer. Reliable contraception methods suggest using one barrier method in combination with one of the following: spermicides, intrauterine device/oral contraceptives

Exclusion Criteria:

1. Baseline erythrodermic, pustular, and guttate psoriasis or any other skin diseases (e.g. eczema) that can affect/complicate assessment of psoriasis treatment
2. Use of the following medications:

   * Prior use of monoclonal antibodies targeting IL17 or its receptor
   * Prior use of more than one drug containing monoclonal antibodies or their fragments
   * Prior use of monoclonal antibodies within 12 weeks before signing the informed consent.
   * Any systemic medications for psoriasis (including glucocorticoids, methotrexate, sulfasalazine, cyclosporine, acitretin, mycophenolate mofetil, аpremilast, calcitriol derivatives, etc.) used within 4 weeks before signing the ICF If prior systemic therapy with non-biologics was stopped due to any reasons, the screening period can be extended up to 8 weeks during which no new non-biologics are allowed.
   * Use of phototherapy within 4 weeks before signing the ICF
   * Topical medications for psoriasis used within 2 weeks before signing the ICF
   * Vaccination with live or attenuated vaccines within 8 weeks before signing the ICF
3. Any active systemic infection or recurrent infection at screening/randomization
4. HIV, hepatitis B, hepatitis C, or syphilis
5. Blood biochemistry abnormalities appearing as:

   1. baseline creatinine \> 2 × ULN
   2. baseline ALT, AST or alkaline phosphatase \> 2.5 × ULN
   3. baseline bilirubin \> 1.5 × ULN
6. WBC count \< 3.0 × 109/L; ANC \< \<2.0× 109/L; platelet count \< 100 × 109/L, or hemoglobin \< 90 g/L at baseline
7. Any psychiatric conditions including severe depressive disorders and/or any history of suicidal thoughts or suicidal attempts ;
8. Signs of clinically significant depression (Beck's score of 16 or more at screening)
9. Alcohol or substance abuse
10. Tuberculosis now or in the past
11. Latent TB infection (positive results of the Diaskintest or QuantiFERON test, or T-spot).
12. Concurrent diseases ongoing at screening that may increase the risk of adverse events during the study or affect the evaluation of psoriasis symptoms (mask, enhance or alter the symptoms of psoriasis, or cause clinical or laboratory signs/symptoms similar to those of psoriasis):

    * active inflammatory diseases or aggravation of chronic inflammatory diseases other than psoriasis
    * Stable angina class III-IV, unstable angina or a history of myocardial infarction within 1 year before signing the informed consent
    * Cardiac failure moderate to severe (NYHA class III-IV)
    * Treatment-resistant hypertension
    * A history of severe asthma or angioedema
    * Moderate to severe respiratory failure, COPD grade ¾
    * Diabetes mellitus with unsatisfactory glycemic control, when the level of glycated hemoglobin HbA1С ≥8% (results are valid if the test was performed at the screening or within 3 months before signing the ICF)
    * The patient has thyrotoxicosis, which persists in the presence of thyreostatic medications, or hypothyroidism despite of the thyroid hormone treatment
    * Systemic autoimmune diseases (including but not limited to SLE, rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective tissue disease , intersection syndrome, etc.)
    * Any other underlying conditions (including but not limited to metabolic, hematologic, hepatic, renal, pulmonary, neurological, endocrine, cardiac, gastrointestinal conditions and infections) that, in the opinion of the investigator, may affect the course of psoriasis, affect the assessment of signs/symptoms of psoriasis, or put patients using the study treatment at additional risk
13. Malignancies with less than 5 years of remission
14. Known severe allergies (anaphylaxis or drug allergy to two or more drug products)
15. Known allergy or intolerance to monoclonal antibody drugs (murine, chimeric, humanized, or human) or any other components of the test drug or comparator
16. Major surgery within 30 days before the screening, or a major surgery being scheduled at any time during the study
17. Severe infections (including those that required hospitalization or parenteral antibacterial/antimycotic/antiprotozoal treatment) within 6 months before signing the ICF
18. Systemic antibacterial/antimycotic/antiprotozoal treatment within 2 months before the signing the ICF
19. More than 4 episodes of respiratory infection within 6 months before signing the ICF
20. Episodes of severe mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, etc.) within 6 months before signing the ICF
21. A history of epileptic attacks or seizures
22. Any concurrent diseases during which, in the investigator's opinion, the study treatment can harm the patient
23. Pregnancy, breastfeeding, or planning for pregnancy while participating in the study
24. Participation in any other clinical study within 3 months before signing the ICF or simultaneous participation in other clinical studies
25. Patients will not be re-enrolled in this study if they were randomized to this study and then discontinue the participation
B: Inclusion Criteria:

* Subject has provided informed consent
* Chronic plaque psoriasis for at least 6 months prior to Screening
* PASI (Psoriasis Area and Severity Index) \>=12 and BSA (body surface area) \>=10% and IGA (Investigator's Global Assessment) score 3 or greater on a 5-point scale
* Candidates for systemic psoriasis therapy and/or phototherapy and/or chemophototherapy
* Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of study drug
* Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of study medication

Exclusion Criteria:

* Subjects with erythrodermic, guttate, pustular form of psoriasis, or drug-induced psoriasis
* Subject has any severe, progressive and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastrointestinal or neurological disease
* Subject has any significant concurrent medical condition or laboratory abnormalities, as defined in the study protocol
* Subject taking prohibited psoriatic medications
* Subject receiving any live vaccines within 8 weeks prior to the Baseline and subjects receiving Bacillus Calmette-Guerin (BCG) vaccination within 1 year prior to study drug administration
* Subject has previously received treatment with any anti-interleukin-17 (anti-IL-17) therapy or has been exposed to more than 1 biological response modifier (limited to anti-tumor necrosis factor (TNF) or IL-12/23) for psoriatic arthritis or psoriasis prior to the Baseline
* Subject has any current sign or symptom that may indicate an active infection (except for common cold)
C: 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.
D: Inclusion Criteria:

* Adults over 18 years of age with a diagnosis of chronic moderate to severe plaque psoriasis for at least 12 months; in generally good health; on stable dose of non-prohibited medications; able to stop current psoriasis therapy (systemic or topical) for several weeks prior to and during study participation.

Exclusion Criteria:

* Serious underlying disease including viral disorders such as hepatitis or HIV or skin condition that would interfere with skin biopsies or evaluation of psoriasis; conditions that could interfere with drug absorption after oral administration; history of malignancy or auto-immune disease.
* Use of oral or injected corticosteroids (steroids).

Answer: C