A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab (AIN457) in Patients With Giant Cell Arteritis (TitAIN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Percentage of Participants in Sustained Remission Until Week 28
研究概览
简要总结
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.
详细描述
This randomized, parallel-group, double-blind, placebo-controlled, multicenter, Phase II study was designed to evaluate the efficacy of secukinumab compared to placebo in combination with a 26-week prednisolone taper regimen in terms of sustained remission in patients with newly diagnosed or relapsing Giant Cell Arteritis (GCA) who were naïve to biological therapy. The study consisted of a Screening Period of up to 6 weeks (maximum duration), a 52-week Treatment Period and an 8-week Safety Follow-up Period
Patients who did not achieve remission by Week 12, experienced a flare after remission or could not adhere to the prednisolone taper regimen entered "escape". Upon entering "escape", patients received prednisolone at a dose determined by the physician's clinical judgment and continued to receive secukinumab or placebo in a blinded manner.
Safety evaluation was included in all visits including two safety follow-up visits performed 8 and 12 weeks after the last study drug administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
干预措施: Prednisolone (Drug)
Secukinumab
Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
干预措施: Secukinumab 300 mg, s.c. (Drug)
Secukinumab
Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
干预措施: Prednisolone (Drug)
Placebo
Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants in Sustained Remission Until Week 28
时间窗: Until week 28
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper regimen. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of Giant Cell Arteritis (GCA) and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or C-reactive Protein (CRP) (\>/=10.0 mg/L) attributable to GCA. Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
次要结局
- Percentage of Participants in Remission at Week 12(Week 12)
- Time to First GCA Flare After Clinical Remission(Up to Week 52 (included))
- Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks(from Baseline to week 28, from baseline to week 52 weeks)
- Percentage of Participants With GCA Who Had Sustained Remission Until Week 52(Until Week 52)
- Number of Participants on Prednisolone Dose ≤ 5mg/Day(Week 19, Week 28, Week 52)
- Physicians Global Assessment (PhGA) of Disease Activity: Change From Baseline Score Via Visual Analogue Scale (VAS)(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52)
- Patients Global Assessment (PGA) of Disease Activity: Change From Baseline Via Visual Analogue Scale (VAS)(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52)
- Change From Baseline in FACIT-Fatigue Scale(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52)
- Change From Baseline in Short-Form (SF)-36 Questionnaire(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52)
- Change From Baseline in EQ-5D-5L (EuroQol 5D) Questionnaire(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, Week 28, Week 52)
- Change From Baseline in C-Reactive Protein (CRP) Level(Baseline, Week 28, Week 52)