A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis

• Status: Completed
• Trial end date: 2021-06-08
• Target enrollment: 0
• Participant gender: All

Summary

This randomized, parallel-group, double-blind, placebo-controlled, multicenter, Phase II study is 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 are naïve to biological therapy.

The study will consist of 6-week (maximum duration) screening period, a 52-week treatment period and a 8-week safety follow-up period.

Patients who do not achieve remission by Week 12, experience a flare after remission or cannot adhere to the prednisolone taper regimen will enter "escape". Upon entering "escape", patients will receive prednisolone at a dose determined by the physician's clinical judgment and continue to receive secukinumab or placebo in a blinded manner.

Safety evaluation will be included in all visits including two safety follow-up visits performed 8 and 12 weeks after the last study drug administration.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Antibodies, Monoclonal; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

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.

Other protocol-defined inclusion/exclusion criteria may apply.