A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Characterizing the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab Following Subcutaneous Administration in Adult Systemic Lupus Erythematosus Subjects With Type I Interferon Test High Result and Active Skin Manifestations.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- 21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
研究概览
简要总结
This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result and active skin manifestations while receiving Standard of Care (SOC) treatment. In addition, the efficacy of anifrolumab on SLE skin manifestations will be characterized.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 through 70 years
- •Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 American College of Rheumatology (ACR) classification criteria with at least one being:
- •Positive antinuclear antibody (ANA) or
- •Elevated anti-dsDNA antibodies or
- •anti-Smith (anti-Sm) antibodies
- •Interferon high test result
- •Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10
- •Currently receiving at least 1 of the following for treatment of SLE:
- •Oral prednisone or equivalent of ≤40 mg/day for a minimum of 2 weeks prior to signing the Informed Consent Form (ICF) and with stable dose for at least 2 weeks prior to randomization
- •Any of the following medications for at least 12 weeks prior to signing the ICF, and at a stable doses for at least 8 weeks prior to randomization: (i) Azathioprine ≤200 mg/day (ii) Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day
- •Must not have signs of active or latent tuberculosis (TB).
- •Must not be pregnant or breastfeeding.
排除标准
- •Active severe or unstable neuropsychiatric SLE
- •Active severe SLE-driven renal disease
- •Any severe herpes infection at any time
- •Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.
- •Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
- •Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF
- •History of cancer, apart from:
- •Squamous or basal cell carcinoma of the skin if successfully treated.
- •Cervical cancer in situ if successfully treated
研究组 & 干预措施
Placebo matching for lower dose of Anifrolumab
1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50
干预措施: Placebo (Drug)
Anifrolumab - Lower dose
1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50
干预措施: Anifrolumab (Drug)
Anifrolumab - Higher dose
2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50
干预措施: Anifrolumab (Drug)
Placebo matching for higher dose of Anifrolumab
2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50
干预措施: Placebo (Drug)
结局指标
主要结局
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
时间窗: Week 12
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. For each individual participant and assessment, the level of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control, as the median of 100-(((baseline-Week 12)/baseline)\*100) for the 21 genes. At a population level, the results are presented as mean the above.
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab
时间窗: Week 12
Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
Maximum Concentration of Anifrolumab in Serum After First Dose
时间窗: Week 0
Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
21-gene Type 1 IFN Signature Score (Fold-change)
时间窗: Week 12
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. Levels of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control.
次要结局
- Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)(Baseline to Week 60)
- Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline(Baseline to Week 60)
- Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline(Baseline to Week 60)
- Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.(Baseline to Week 60)
- Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)(Baseline to Week 52)
- Change From Baseline for Vital Signs(Baseline to Week 60)
- Number of Participants With Antidrug Antibody (ADA)(Baseline to Week 52)
- Change From Baseline for Physical Examination(Baseline to Week 60)
- Change From Baseline for 12-lead ECG(Baseline to Week 52)
- Number of Participants With Neutralizing Antibodies (nAb)(Baseline to Week 52)
- Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline(Baseline to Week 60)
- Value of Total Protein Urinalysis Test to Detect Change From Baseline(Baseline to Week 60)
- Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)(Baseline to Week 60)
- Value of Haemoglobin Blood Test to Detect Change From Baseline(Baseline to Week 60)
- Value of Haematology Blood Tests to Detect Change From Baseline(Baseline to Week 60)