Giant Cell Arteritis MedDRA version: 23.1 Level: PT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: Cosentyx
Product Name: Secukinumab
Product Code: AIN457
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SECUKINUMAB
CAS Number: 1229022-83-6
Current
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study must meet all of the following criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study. 3. Male or non-pregnant, non-lactating female patients at least 50 years of age. 4. 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. 5. 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 (=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: Patients who fulfill any of the following criteria are not eligible for inclusion: 1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. 2. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for a minimum of 20 weeks after the last dose of secukinumab. 3. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. 4. 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). 5. Patients who have previously been treated with any biologic agent including but not limited to tocilizumab, sirukumab, abatacept, or tumor necrosis factor alpha (TNFa) inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab). 6. Patients who have previously been treated with tofacitinib or baricitinib. 7. Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline. 8. Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to Baseline. 9. Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or mycophenolate mofetil within 4 weeks of Baseline. 10. 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. 11. Patients treated with an alkylating agent except for cyclophosphamide as mentioned above. 12. Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA. 13. 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. 14. Patients requiring chronic (i.e. not occasional “prn”) high potency opioid analgesics for pain management. 15. Patients treated with any investigational agent within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline. 16. Contraindication or hypersensitivity to secukinumab. 17. Active ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of secukinumab therapy. 18. 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 immunocomprises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy. 19. Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (= 160/95 mmHg), congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes. 20. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFTs) such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or serum bilirubin. 21. History of renal trauma, glomerulonephritis, or patients with one kidney only, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of secukinumab compared to placebo, in combination with a 26-week prednisolone taper regimen, based on the proportion of patients with GCA who have sustained remission until week 28.;Primary end point(s): Proportion of GCA patients in sustained remission at Week 28.;Timepoint(s) of evaluation of this end point: Week 28;Secondary Objective: To evaluate the efficacy of secukinumab in combination with a 26-week prednisolone taper regimen vs. placebo in patients with GCA measured by: • Remission rate at Week 12 • Time to first flare after remission • Cumulative corticosteroid dose up to Week 28 and 52 • Patients in sustained remission up to Week 52 • Proportion of patients on prednisolone dose = 5mg/day at Week 19/28/52 • Changes from baseline in disease activity and quality of life measures at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 for the following: - Physician’s global assessment (PhGA) visual analog scale (VAS) - Patient reported outcomes (PROs): Patient global assessment (PGA) VAS; Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue); Short form 36 (SF36); EuroQoL 5D (EQ-5D) Laboratory parameters (Baseline vs. Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52): CRP; ESR To evaluate the safety/tolerability and immunogenicity of secukinumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy • Remission rate at Week 12 • Time to first flare after remission • Cumulative corticosteroid dose up to Week 28 and 52 • Patients in sustained remission up to Week 52 • Proportion of patients on prednisolone dose = 5mg/day at Week 19/28/52 • Changes from baseline in disease activity and quality of life measures at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 for the following: - Physician’s global assessment (PhGA) visual analog scale (VAS) - Patient reported outcomes (PROs): Patient global assessment (PGA) VAS; Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue); Short form 36 (SF36); EuroQoL 5D (EQ-5D) - Laboratory parameters (Baseline vs. Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52): CRP; ESR - Safety/tolerability and immunogenicity of secukinumab ;Timepoint(s) of evaluation of this end point: Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | — |
Countries
Germany
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed