Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed IL-17A Therapies
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Brodalumab
Intervention description: Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Intervention MeSH terms: Brodalumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Psoriasis; brodalumab

Summary:

      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.
    

Eligibility criteria:

        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.