A Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis
Condition: Psoriasis Vulgaris
MeSH terms: Psoriasis
Intervention: Brodalumab; Fumaric acid esters
Intervention description: Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2-antibody that binds with high affinity to human interleukin 17 receptor A (IL-17RA).> Blocking IL-17RA inhibits IL-17 cytokine-induced responses and results in reduced or normalised inflammation of the skin in subjects with psoriasis.; Fumaric acid esters have been used to treat psoriasis since 1959. Systemic therapy with fumaric acid esters is based on an established dosing scheme with a gradual increase to improve tolerability, especially with regards to gastrointestinal side effects.
Intervention MeSH terms: Brodalumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 210.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective is to demonstrate added benefit of brodalumab versus a selected
      systemic comparator in treatment of moderate to severe plaque psoriasis in Germany in
      subjects who have not previously received systemic treatment for psoriasis. > Fumaric acid
      esters have been selected as the comparator because it is an established systemic treatment
      of psoriasis in Germany.>
    

Eligibility criteria:

        Main Criteria for Inclusion:>

          -  Men or women ≥18 years of age at the time of screening.>

          -  Subjects with chronic plaque type psoriasis diagnosed at least 6 months before
             randomisation.>

          -  Subjects with moderate to severe plaque psoriasis in whom topical therapy is not
             adequate and who are candidates for systemic therapy, defined at randomisation by PASI
             >10, affected BSA >10%, and DLQI >10.>

          -  Subject has no known history of active tuberculosis.>

          -  Subject has a negative test for tuberculosis taken at screening (negative Quantiferon
             test).>

          -  Subject and/or subject's designee is/are capable of administering subcutaneous
             injections.>

        Main Criteria for Exclusion:>

          -  Previous or current systemic treatment of plaque psoriasis or known contraindication
             for systemic therapy.>

          -  Previous or current PUVA (psoralens and ultraviolet A) therapy.>

          -  Washouts and non-permitted drugs:>

               1. Have received phototherapy (UVA light therapy without psoralens, UVB light
                  therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or>

               2. Have had topical psoriasis treatment within 2 weeks of baseline (exceptions:
                  bland emollients without urea or beta or alpha hydroxy acids)>

               3. Have received any biologic immune modulating treatments used for indication other
                  than psoriasis within 4 weeks of baseline or within a period of 5 half-lives of
                  the IMP, whichever is longer>

               4. Have received any other systemic immune modulating treatment (including but not
                  limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or
                  parenteral corticosteroids etc. used for indications other than psoriasis) within
                  4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is
                  longer.>

          -  Subjects with any of the following laboratory abnormalities at screening:>

               1. Leukocyte cell count below 3×10^9/L or lymphocyte count below 0.7×10^9/L>

               2. Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2× ULN (upper
                  level of normal limit)>

               3. Absolute neutrophil count < 2×10^9/L>

               4. Serum creatinine > ULN.>

          -  History of depressive disorder within the last 2 years including current
             antidepressive treatment.>

          -  Subjects with a history of suicidal behaviour (suicide attempt). >

          -  Any suicidal ideation of severity 4 or 5 based on the eC-SSRS questionnaire at
             screening.>

          -  A PHQ-8 score of ≥10 corresponding to moderate to severe depression at screening.>