A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis
Condition: Giant Cell Arteritis
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
Intervention: Secukinumab 300 mg, s.c.; Prednisolone; Placebo
Intervention description: Secukinumab 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.; Prednisolone was provided as tablets (1 mg, 5 mg, 10 mg, 20 mg tablets) for daily administration as tapered regimen from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 (last dose); Placebo 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.
Intervention MeSH terms: Prednisolone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 52.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: GCA; ain457; Secukinumab; Subcutaneous; Vessel Inflammation; corticosteroid tapering; newly diagnosed or relapsing giant cell arteritis; prednisolone taper regimen; "escape"

Summary:

      This study was designed to evaluate the efficacy and safety of secukinumab compared to
      placebo to maintain disease remission up to 28 weeks including corticosteroid tapering, as
      well as up to 1 year (52 weeks) in patients with newly diagnosed or relapsing giant cell
      arteritis (GCA) who were naïve to biological therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Diagnosis of GCA classified according to the following criteria:

          -  Age at onset of disease ≥ 50 years.

          -  History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L.

          -  Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal
             artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw
             pain upon mastication) AND/OR symptoms of polymyalgia rheumatica (PMR) defined as
             shoulder and/or hip girdle pain associated with inflammatory morning stiffness

          -  Temporal artery biopsy revealing features of GCA AND/OR

          -  evidence of large-vessel vasculitis by angiography or cross-sectional imaging study
             such as magnetic resonance angiography (MRA), computed tomography angiography (CTA),
             positron emission tomography-computed tomography (PET CT), or ultrasound

        Patients with new onset GCA or relapsing GCA (Definition new onset: diagnosis of GCA within
        6 weeks of Baseline Visit; Definition relapsing GCA: diagnosis of GCA (in accordance with
        inclusion criterion no. 4) > 6 weeks before Baseline Visit and in the meantime achieved
        remission (absence of signs and symptoms attributable to GCA and normalization of ESR (< 30
        mm/hr) and CRP (<10.0mg/L) included) including previous treatment with ≥ 25 mg/day
        prednisolone equivalent for ≥ 2 weeks.)

        Active disease as defined by the presence of signs and symptoms of GCA (cranial or PMR) and
        elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L, attributed to active GCA within 6 weeks of
        Baseline.

        Prednisolone dose of 25-60 mg/day at Baseline.

        Exclusion Criteria:

        Previous exposure to secukinumab or other biologic drug directly targeting
        Interleukin(IL)-17 or IL-17 receptor.

        Patients treated with any cell-depleting therapies including but not limited to anti-CD20
        or investigational agents (e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19).

        Patients who have previously been treated with any biologic agent including but not limited
        to tocilizumab, sirukumab, abatacept, or tumor necrosis factor alpha (TNFα) inhibitors
        (infliximab, adalimumab, etanercept, certolizumab, golimumab).

        Patients who have previously been treated with tofacitinib or baricitinib.

        Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to
        Baseline.

        Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to
        Baseline.

        Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or
        mycophenolate mofetil within 4 weeks of Baseline.

        Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine
        washout has been performed in which case the patient must be treated within 4 weeks of
        Baseline.

        Patients treated with an alkylating agent except for cyclophosphamide as mentioned above.

        Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.

        Chronic systemic glucocorticoid therapy over the last 4 years or longer; or inability, in
        the opinion of the investigator, to withdraw glucocorticoid therapy through
        protocol-defined taper regimen due to suspected or established adrenal insufficiency.

        Patients requiring chronic (i.e. not occasional "prn") high potency opioid analgesics for
        pain management.

        Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic,
        pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which
        in the opinion of the investigator immunosuppressed the patient and/or places the patient
        at unacceptable risk for participation in an immunomodulatory therapy.

        History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum
        creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).

        Screening total white blood cell (WBC) count < 3000/μL, or platelets < 100 000/μL or
        neutrophils < 1500/μL or hemoglobin < 8.3 g/dL (83 g/L).

        Major ischemic event, unrelated to GCA, within 12 weeks of screening.

        Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at
        screening or randomization.

        Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study
        participation until 12 weeks after last study treatment administration.