This study will compare the efficacy and safety of DFD-06 Cream to Vehicle Cream for topical treatment of moderate to severe plaque psoriasis after 3, 7, and 14 days of treatment.

This study will be a multicenter (approximately 30 sites), randomized, vehicle-controlled, double-blind, and parallel group design. Approximately 264 subjects with moderate to severe plaque psoriasis will be randomized to treatment with DFD-06 Cream or Vehicle Cream. Subjects will use study product twice daily for 14 days. Subject visits are scheduled at Screening, Baseline (Day 1) and Days 4, 8, and 15. Clinical determinations of disease severity will be performed using the total sign score (TSS) for the target lesion and Investigator Global Assessment (IGA) for overall severity.

Inclusion Criteria:

1. Subject understands the study procedures and agrees to participate by giving written informed consent. Subjects must be willing to authorize use and disclosure of protected health information collected for the study.
2. Subject must be at least 18 years of age.
3. Subject must present with a clinical diagnosis of stable (at least 3 months) plaque-type psoriasis.
4. Subject with psoriasis involving 3% or greater BSA, not including the face, scalp, groin, axillae and other intertriginous areas.
5. Subject must have an IGA grade of 3 or 4 (moderate to severe) at the Baseline Visit.
6. Female subjects of childbearing potential must agree to use contraception during the study which can include abstinence with an adequate secondary option should the subject become sexually active. All women of childbearing potential must complete a urine pregnancy test (test must have a sensitivity of at least 25mIU/ml for human chorionic gonadotropin) at the Baseline Visit (Visit 2) and the test result must be negative to be eligible for enrollment.
7. Subject must be in good general health as determined by the investigator and supported by the medical history and normal or not clinically significant abnormal vital signs (blood pressure and pulse).

Exclusion Criteria:

1. Current diagnosis of unstable forms of psoriasis including guttate, erythrodermic, exfoliative or pustular psoriasis.
2. Other inflammatory skin disease that may confound the evaluation of the plaque psoriasis (e.g., atopic dermatitis, contact dermatitis, tinea corporis).
3. Presence of pigmentation, extensive scarring, or pigmented lesions or sunburn which could interfere with the rating of efficacy parameters.
4. History of psoriasis unresponsive to biological or topical treatments.
5. History of organ transplant requiring immunosuppression, HIV, or other immunocompromised state.
6. Use within 180 days prior to Baseline Visit of biologic treatment for psoriasis (e.g., infliximab, adalimumab, etanercept, ustekinumab, secukinumab, or alefacept).
7. Have received treatment for any type of cancer within 5 years of the Baseline Visit except skin cancer and cervical cancer (in situ) are allowed if at least 1 year before the Baseline Visit.
8. Use within 60 days prior to the Baseline Visit of: 1) systemic or topical immunosuppressive drugs (e.g., tacrolimus, pimecrolimus), 2) systemic antipsoriatic treatment (e.g., methotrexate, cyclosporine, hydroxyurea) or 3) oral retinoids (e.g., acitretin, isotretinoin).
9. Use within 30 days prior to the Baseline Visit of: 1) systemic steroids, 2) PUVA therapy, 3) systemic anti-inflammatory agents (e.g., mycophenolate mofetil, sulfasalazine, 6-thioguanine), or 4) UVB therapy. Inhaled, intraocular, and intranasal steroids are allowed.
10. Use within 14 days prior to the Baseline Visit of: 1) topical antipsoriatic drugs (e.g., salicylic acid, anthralin, coal tar, calcipotriene), 2) topical retinoids (e.g., tazarotene, tretinoin) or 3) topical corticosteroids.
11. Subjects who have participated in a study of an investigational drug 60 days prior to the Baseline Visit.