Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Multicentre, Double-Blind, Placebo-Controlled Study of ISA247 in Plaque Psoriasis Patients
Brief Summary: The purpose of this study is to determine which dose of voclosporin is effective in the treatment of plaque psoriasis compared to placebo.


Options:
A: 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)
B: 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.
C: Inclusion Criteria:

* Plaque psoriasis ≥ 6 months prior to screening.
* Diagnosis of stable, plaque psoriasis; i.e. psoriasis must not be spontaneously improving or worsening in the 4 weeks prior to the screening visit.
* Plaque psoriasis involving ≥10% of the body surface area (BSA) at screening and prior to randomization at the day 0 visit.
* PASI score ≥10 at screening and prior to randomization at the day 0 visit.
* Not pregnant or nursing or planning to become pregnant during the course of the study.
* Sexually active women of childbearing potential or less than 1 year post-menopausal and sexually active men who are not surgically sterile must use a reliable form of birth control during study treatment and for at least 3 months after the last dose of study drug. Surgically sterile females are not considered to be of childbearing potential. Reliable forms of birth control include oral or depot contraceptives, and double-barrier methods.
* Written informed consent prior to washout and screening procedures.
* Able to keep study appointments and cooperate with all study requirements, in the opinion of the investigator.

Exclusion Criteria:

* Has generalized erythrodermic, guttate, or pustular psoriasis.
* Have other dermatoses that would interfere with the evaluation of psoriasis, at the discretion of the investigator.
* A current malignancy or history of malignancy within 5 years or a history of lymphoma at any time. Subjects can be enrolled with a history of squamous or basal cell carcinoma that has been surgically excised or removed with curettage and electrodesiccation.
* Has current, uncontrolled bacterial, viral, or fungal infections that require intravenous antibiotics or antifungals or had had such infections within 60 days prior to screening.
* A history of streptococcal infection that required oral antibiotics within 30 days prior to screening.
* A known history of tuberculosis.
* Serologic evidence or known latent human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) virus.
* Uncontrolled hypertension as defined by systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥ 90 mm Hg.
* MDRD GFR ≤ 60 ml/min.
* Variation between the screening and Visit 1 GFR ≥30%.
* Alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase ≥ 3x upper limit of normal (ULN).
* White blood cell count ≤ 2.8 x 109/L.
* Triglycerides ≥ 3x ULN.
* Requires the following prohibited medications or treatments during the washout or treatment period: drugs potentiating the nephrotoxicity of voclosporin such as NSAID's or ACE inhibitors, drugs interfering with its pharmacokinetics; drugs considered to contribute to psoriasis flare; or, systemic and topical psoriasis medication (including psoralen/ultraviolet A light treatment) that may interfere with assessment of study drug efficacy.
* Has used any investigational drug or device within 28 days or 5 half lives (whichever is longer) prior to the screening visit.
* Has taken biological agent(s), except flu shots, tetanus shots, or boosters, within 3 months of the start of treatment. Biological agents include any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries of man.
* Previous exposure to voclosporin.
* A history of clinically defined allergy to cyclosporine or any of the constituents of the voclosporin formulation (vitamin E, medium chain triglyceride oil, Tween 40, ethanol).
* A history of alcoholism or drug addiction within 1 year prior to study entry.
* Weighs \<45 kg (99 lbs) or \> 140 kg (308 lbs).
* A history of disease, including mental/emotional disorder that would interfere with the subject's participation in the study, or that might cause the administration of ISA247 to pose a significant risk to the subject, in the opinion of the investigator.
D: Inclusion Criteria:

* Have a diagnosis of plaque-type psoriasis (with or without \[Psoriatic Arthritis\]PsA) for at least 6 months before the first administration of study drug
* A woman of childbearing potential must have a negative urine pregnancy test at screening and at Week 0 and agree to urine pregnancy testing before receiving injections
* Agree not to receive a live virus or live bacterial vaccination during the study, or within 3 months after the last administration of study drug
* Agree not to receive a Bacille Calmette-Guérin (BCG) vaccination during the study, or within 12 months after the last administration of study drug
* Agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study

Exclusion Criteria:

* Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
* Has previously received guselkumab or secukinumab
* Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (example bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), fungal infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers
* Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance; or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly
* Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins

Answer: C