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. Males or females, ≥ 18 years of age at the time of signing the informed consent document.
2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the informed consent.
5. Have moderate plaque psoriasis at screening and baseline as defined by

   1. BSA (Body Surface Area)5% to 10% and
   2. sPGA (Physician's Global Assessment) 3 (moderate) based on a 0 to 5 point scale
6. Must be in general good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, and clinical laboratories.
7. No prior exposure to systemic treatments or biologics for the treatment of psoriatic arthritis, psoriasis, or any other indication that could impact the assessment of psoriasis.
8. Females of childbearing potential (FCBP)must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
9. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) while on investigational product and for at least 28 days after the last dose of investigational product

Exclusion Criteria:

1. Other than psoriasis, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,immunologic disease, or other major disease that is currently uncontrolled.
2. Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
3. Any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, guttate, inverse, or pustular psoriasis), other than plaque psoriasis.
4. Prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
5. Pregnant or breast feeding.
6. Active substance abuse or a history of substance abuse within 6 months prior to signing the informed consent.
7. Malignancy or history of malignancy, except for:

   1. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
   2. treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of signing the informed consent.
8. Topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol). Use of phototherapy within 4 weeks prior to randomization.
9. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
10. Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study.
11. Prior treatment with apremilast.
B: Inclusion Criteria:

* Subject has had stable moderate to severe plaque psoriasis for at least 6 months
* Subject has received at least one previous phototherapy or systemic psoriasis therapy or has been a candidate to receive phototherapy or systemic psoriasis therapy in the opinion of the investigator.
* Subject has involved BSA ≥ 10% and PASI ≥ 12 at screening and at baseline.

Exclusion Criteria:

* Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, medication-induced, or medication-exacerbated psoriasis.
* Evidence of skin conditions at the time of the screening visit (eg, eczema, guttate psoriasis) that would interfere with evaluations of the effect of IP on psoriasis.
* Subject has any active CTCAE grade 2 or higher infection
* Subject has a significant concurrent medical condition or laboratory abnormalities, as defined in the study protocol.
* Subject has used the following therapies within 14 days of the first dose: UVB therapy or topical psoriasis therapies other than Class I or II topical steroids
* Subject has used the following therapies within 28 days of the first dose: Class I or II topical steroids, UVA therapy (with or without psoralen), or systemic psoriasis therapies
* Subject has used the following therapies within 3 months of the first dose: adalimumab, alefacept, etanercept, infliximab, certolizumab, or live vaccines
* Subject has used an anti-IL12/IL23 inhibitor within 6 months of the first dose
* Subject has previously used an anti-IL17 biologic therapy, efalizumab, or rituximab
C: Inclusion Criteria:

1. Males and females 18 years of age and older.
2. Subject completed the VIP Study
3. Subject willing and able to avoid prolonged exposure of skin affected by psoriasis to natural or sunlight or tanning beds during the course of the study
4. Subject is willing and able to avoid topical or systemic prescription treatments for psoriasis besides adalimumab during the course of the study
5. Women are eligible to participate in the study if they meet one of the following criteria:

   1. Women of childbearing potential must undergo pregnancy testing during the baseline visit and agree to use one of the following methods of contraception throughout the 13-month study:

      * Oral contraceptives;
      * Transdermal contraceptives
      * Injectable or implantable methods
      * Intrauterine devices
      * Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or
      * Vasectomized partner
      * Subjects using oral or parental forms of contraceptives must have been using those methods of birth control for at least three months prior to the baseline visit.
   2. Women who have undergone tubal ligation
   3. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate
   4. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study.
6. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination.
7. Able and willing to give written informed consent and to comply with requirements of this study protocol.

Exclusion Criteria:

1. Previous adverse event following exposure to a TNF-alpha antagonist that led to discontinuation of the TNF inhibitor and contraindicates future treatment.
2. Previous lack of response to a TNF-alpha antagonist led to discontinuation.
3. Diagnosis of erythrodermic psoriasis, generalized pustular psoriasis, or medication-induced or medication-exacerbated psoriasis.
4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
5. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
6. Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study.
7. History of diabetes mellitus, type 1 or type 2 (patients with type 2 diabetes may be enrolled if the duration of diabetes is \<10 years and HbA1c is \<7.0%)
8. Uncontrolled hypertension, with measured systolic blood pressure \>180 mmHg or diastolic blood pressure \>90 mmHg
9. History of demyelinating diseases or lupus.
10. Subject has infection or risk factors for severe infections, for example:

    * Known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections;
    * Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection;
    * Active tuberculosis (TB) disease;
    * Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results as determined within 6 months of the baseline visit for VIP-E; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously.
    * Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline;
    * Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline;
    * Subject will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
11. Subject has history of hematological or solid malignancy within the past five years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.
12. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
13. Clinic laboratory analyses showing any of the following abnormal results:

    * Hemoglobin (Hgb) \< 10 g/dL in females or \<12 g/dL in males;
    * White blood cell (WBC) count \<2.5 x 109/L

      * Subject can be included if WBC count is \<2.5 x x 109/L and absolute neutrophil count (ANC) is \>1000 cells / mm3.
    * WBC count \> 15 x 109/L;
    * Platelet count \< 100 x 109/L;
    * Serum aspartate transaminase (AST) or alanine transaminase (ALT) \>2.5 upper limits of normal (ULN);
    * Serum total bilirubin ≥2 mg/dL (≥26 µmol/L)
14. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
15. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to baseline and remain stable throughout the duration of the study.
D: 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.

Answer: D