This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Forty patients will be enrolled in this 16-week open-label study. Patients will receive 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. The primary efficacy endpoint will be the proportion of patients achieving a score of "0-clear" or "1-almost clear" in the sPGA score after 16 weeks of treatment. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab.

This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Failure of IL-17A therapy will be defined as previous treatment with either secukinumab or ixekizumab for at least 3 months without achieving PASI-75 response or a 50% loss of original improvement. Forty patients will be enrolled in this 16-week open-label study. Patients will be enrolled at three to four different sites in the US. After enrollment, study visits will occur at monthly intervals, with patients receiving 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. At each visit, patients will be evaluated for change in sPGA (Physician's Global Assessment), PASI score, and any signs or symptoms of adverse events. Laboratory screening will include tests for tuberculosis and neutropenia. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab. Efforts will be made to provide drug to these study patients, including those who do not have insurance.

Inclusion Criteria:

• Male or female subject at least 18 years of age
• Subject is able to provide written informed consent and comply with the requirements of this study protocol.
• Have both a sPGA score of ≥3 and BSA ≥ 5% prior to randomization.
• Subjects who are women of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Acceptable methods of birth control include intrauterine device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must have been initiated at least 1 month before entering the study); tubal ligation; abstinence and barrier methods with spermicide. Otherwise, if not of childbearing potential, subjects must: have a sterile or vasectomized partner; have had a hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for at least a year.
• Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) negative at the time of screening, or if patient has a history of positive PPD or QuantiFERON, he/she has initiated or completed the appropriate prophylaxis.
• Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history and laboratory profile.
• Subject has previously failed treatment with an IL-17A agent, secukinumab or ixekizumab, (where available, defined as previous treatment with either drug for at least 3 months without achieving PASI-75 response or a 50% loss of original improvement).
• Last administration of secukinumab or ixekizumab ≥ 28 days prior to Baseline.

Exclusion Criteria:

• Have predominantly pustular, erythrodermic, and/or guttate forms of psoriasis.
• History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) at Screening. Subjects with a positive or indeterminate PPD or QFT test may participate in the study if a full tuberculosis work up (according to local practice/guidelines) is completed within 12 weeks prior to randomization and establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated at least for 4 weeks prior to randomization and the course of prophylaxis is planned to be completed.
• Subjects with a history of HIV, or history of positive HCV or HBV
• Use of any of the following therapies within 4 weeks prior to Baseline (Visit 2): systemic non-biologic psoriasis therapies (including, but not limited to): psoralens and ultraviolet A (PUVA) therapy, cyclosporine, methotrexate, azathioprine, corticosteroids, apremilast, tofacitinib, oral retinoids, mycophenolate mofetil, sirolimus; 1, 25 dihydroxyvitamin D analogs; or phototherapy (including UVB or self-treatment with tanning beds or therapeutic sunbathing) or topical psoriasis therapy with psoralens.
• Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline (Visit 2).
• Use of any investigational drug or any systemic drug for psoriasis within four weeks prior to Baseline (Visit 2).
• Serious concomitant illness that could require the use of systemic corticosteroids or otherwise interfere with the patient's participation in the trial.
• Clinically important deviation as judged by the investigator (such WBC< 3) from normal limits in physical examination, vital sign measurements, clinical laboratory tests results, not associated with a chronic, well-controlled medical condition.
• Any active live-vaccines 3 months prior to baseline and throughout the study.
• Have a current or history of lymphoproliferative disease within 5 years prior to Baseline (Visit 2); or have current or history of any malignant disease within 5 years prior to Baseline (Visit 2).
• History of suicide attempt, or are clinically judged by investigator to be at risk of suicide.
• History of Crohn's disease.
• Had a serious infection, been hospitalized, or received IV antibiotics for an infection, within 12 weeks prior to Baseline (Visit 2).
• Known immunodeficiency, or history of infection typical of an immunocompromised host.
• At screening, have a neutrophil count <1500 cells/uL.
• At screening, have a lymphocyte count <800 cells/uL.
• At screening, have a platelet count <100,000 cells/uL.
• At screening, have a total white blood count (WBC) < 3000 cells/uL.
• At screening, have a hemoglobin <8.5 g/dL.
• Have donated >450 mL of blood within 4 weeks prior to screening (Visit 1), or intend to donate blood during the course of the study.
• Women who are lactating or breastfeeding.
• Any other condition that precludes the patient from following and completing the protocol, in the opinion of the investigator.

16 weeks