Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety & Tolerability of Two Doses of ACT-128800, an Oral S1P1 Receptor Agonist, Administered up to Twenty-eight Weeks in Patients With Moderate to Severe Chronic Plaque Psoriasis
Brief Summary: This study will assess the efficacy, safety and tolerability of two doses of ACT 128800 in patients with moderate-to-severe chronic plaque psoriasis.


Options:
A: Inclusion Criteria:

1. Able and willing to give written informed consent.
2. Men or women is ≥18 and ≤ 75 years of age at time of screening.
3. Stable moderate to severe plaque psoriasis for at least 6 months before Screening.
4. Moderate to severe psoriasis as defined at Baseline by:

   BSA of ≥ 10% involvement at the Baseline visit. PGA score of ≥ 3 at the Baseline visit. PASI score of ≥ 12 at the Baseline visit.
5. Acceptable to systemic therapy, as judged by the investigator.
6. Previously received at least one traditional psoriasis treatment (for example, methotrexate, cyclosporine A, psoralen plus UVA or UVB, tretinoin, Chinese medicine, etc.), and was insensitive, intolerant, contraindicated to, or failed the treatment, as judged by the investigator.
7. At time of screening, lab tests have to meet the following:

   1. Hemoglobin ≥ 90 g/L
   2. WBC ≥ 3.5 × 10\^9/L
   3. Platelets ≥ 100 × 10\^9/L
   4. Serum creatinine ≤1.5 × upper limit of normal (ULN)
   5. AST and ALT ≤2 × ULN
8. For women of child-bearing age, a negative serum pregnancy test during screening, and a negative urine pregnancy test at baseline.
9. During the study to 150 days after the last dose of study medicine, subjects should use effective contraceptive measures
10. Subject is willing and able to comply with the visit schedule and other requirements of the study.

Exclusion Criteria:

1. At screening visit, subjects with erythrodermic psoriasis, pustule psoriasis, bit type psoriasis, drug-induced psoriasis, other skin lesions (such as eczema), other systemic autoimmune inflammatory lesions, which may affect the efficacy evaluation of the treatment.
2. The subject has surgery plan during the study period (excluding surgery that is related to the study disease), except that there will be no increased risk for the subjects or no influence on the study treatment or adherence to the study as judged by the investigator.
3. Participants were given the following treatment, or will be required to receive the following treatment during the study period:

   1. The use of topical drugs within the first two weeks before screening;
   2. The use of UVA and/or UVB treatment, and non-biological drugs (such as methotrexate, cyclosporin, tretinoin, traditional Chinese medicine, proprietary Chinese medicine, etc) within the first four weeks before screening;
   3. In the first 4 weeks before screening, the use of Etanercept or Etanercept; in the first 12 weeks before screening, the use of other biological agents
4. Subjects had live vaccination in the first four weeks before screening, or have the intention to receive live vaccination during the study period.
5. Subjects with history of mycobacterium tuberculosis infection, or with active tuberculosis, or with latent tuberculosis, or with suspected tuberculosis infection judged by clinical phenotypes.
6. Anti-HIV antibody positive, or antibody positive for treponema pallidum, or anti-HCV antibody positive, or HBV HBsAg and/or HBcAb positive at screening.
7. Accompanying active infection or history:

   1. Within 4 weeks before screening, systemic anti-infection treatment;
   2. Within 8 weeks before screening, severe infection with hospitalization or intravenous anti-infection treatment;
   3. Recurrent, chronic, or other active infections, which may increase the study risk as evaluated by the investigator.
8. Known malignancy or history of malignancy (except for the following: in situ skin squamous carcinoma after thorough treatment with no sign of recurrence, basal cell carcinoma, cervical cancer in situ, or skin squamous carcinoma at least five years prior to randomization with no signs of recurrence after treatment).
9. Ongoing, severe, progressive, or uncontrolled diseases, including but not limited to diseases at the endocrine system, blood system, urinary system, liver and gallbladder, respiratory system, nervous system, cardiovascular system, gastrointestinal system or infectious diseases, with increased risk to participate the study as assessed by the investigator.
10. The subjects with active neuropathies, such as multiple sclerosis, Guillain-Barre Syndrome, optic neuritis, transverse myelitis, or neurological symptoms suggestive of the demyelinating diseases of the central nervous system.
11. Moderate to severe heart failure (NYHA III/IV)
12. History of allergic reactions to the active components of the study drugs (HLX03 and adalimumab (Humira®)) and their formulation gradients, or medicines belonging to the same pharmacology and biological category.
13. Participated in another study and received an experimental related drugs within the previous 3 months before screening.
14. Pregnant or lactating women.
15. History of alcohol or substance abuse or dependence, mental disorders.
16. Any condition that will lead to no treatment benefit or affect efficacy evaluation, as judged by the investigator.
B: Inclusion Criteria:

* Adult males and females aged 18 to 60 years (inclusive) with moderate to severe chronic plaque psoriasis who require systemic treatment.

Exclusion Criteria:

* Patients with other forms of psoriasis and patients who are currently treated for autoimmune disorders other than psoriasis.
* Systemic or topical treatments for psoriasis other than emollients. Ongoing bacterial, viral or fungal infections.

History or presence of malignancy.

* Additional inclusion and exclusion criteria apply with respect to medical conditions and concomitant treatments which could affect patients' risk from participating in the study.
C: Inclusion criteria:

* Male or female patients with age ≥18 years at screening.
* Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before the first administration of study drug.
* Have stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis at both Screening and Baseline (Randomisation):

  1. Have an involved body surface area (BSA) ≥10% and
  2. Have a Psoriasis Area and Severity Index (PASI) score ≥12 and
  3. Have a static Physician Global Assessment (sPGA) score of ≥3.
* Must be candidates for systemic therapy or phototherapy for psoriasis treatment, as assessed by the investigator.
* Must be a candidate for treatment with Stelara® (ustekinumab) according to local label.

Exclusion criteria:

* Patients with:

  1. non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)
  2. current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium)
  3. active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis that might confound trial evaluations according to investigator's judgment
* Previous exposure to BI 655066.
* Previous exposure to ustekinumab (Stelara®).
D: Inclusion Criteria:

1. Signed and personally dated written informed consent
2. Male / female
3. Aged 18 years or older
4. With a diagnosis of chronic plaque psoriasis for at least 12 months before enrollment in the study
5. With the severity of psoriasis defined as moderate to severe, as reflected in meeting all the following criteria:

   * PASI \> 10
   * BSA (body surface area) \> 10 %
   * PGA moderate to severe
6. With general good health, or a stable medical condition not considered likely to interfere with the conduct of the clinical study, as determined by the investigator based upon results of medical history, laboratory results and physical examination
7. Prior therapy with systemic drugs for psoriasis or naïve to systemic treatment but identified as a candidate for systemic treatment.
8. With a complete record of at least 12 months of other previous topical and systemic treatments, if any
9. Adhering to the following wash-out periods Topical treatment Wash-out Period Corticosteroids Vitamin A analogues Vitamin D analogues Anthracene derivatives Tar Salicylic acid preparations 2 weeks Systemic treatment Biologics with antipsoriatic activity 3 months Conventional systemic antipsoriatic drugs and phototherapy 1 month Immunosuppressive medication (if not covered by any of the above treatments) Cytostatics 6 months Medications with known harmful influences on the kidneys 5 x halftime
10. For females of child-bearing potential: a negative serum pregnancy test at screening and willing to use highly effective methods of birth control during the study period and for 60 days after the last dose of investigational product. Additionally they must agree to have pregnancy tests while on study medication. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
11. Males (including those who have had vasectomy) must agree to use barrier contraception while on study medication
12. Willing to keep sun exposure reasonably constant and not to use tanning booths or other UV light sources for the duration of the trial

Exclusion Criteria:

1. For females: pregnant or lactating
2. With a diagnosis of guttate, erythrodermic or pustular psoriasis
3. With a hematological abnormality as follows: platelet count \< 100,000/mm3, WBC count \< 3,000 cells/ mm3, lymphocyte count \< 1.000/µl, hemoglobin, hematocrit, or red blood cell count outside 30 % of the upper or lower limits of normal for the lab
4. With a history of malignancies except for non melanoma skin cancer
5. Suffering from significant gastrointestinal problems (ulcers, diarrhea, etc.)
6. Known to have significant renal impairment
7. Are detected to have abnormal liver enzymes \>2x the upper limit of the normal range
8. With active infectious disease
9. On systemic therapy with drugs that may interfere with the investigational products taken within the defined wash-out period
10. With a history of alcohol or drug abuse
11. Known HIV-positive status or suffering from any other immunosuppressive disease
12. Known to be hypersensitive to ingredients of the investigational products
13. Previous enrolled in this study or participating in any other drug investigational trial within the 30 days (or five half-lives whichever is longer) prior to enrolment.
14. Not willing to give consent for transmission of personal "pseudonymised" data
15. Unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study

Answer: B