A Multicenter, Randomized, Parallel-group, Double-blind, Two-arm, Phase III Study to Evaluate the Safety and Efficacy of Anifrolumab Compared with Placebo in Male and Female Participants 18 to 70 Years of Age Inclusive with Systemic Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 61
- 主要终点
- Proportion achieving Revised Composite Response Index in Systemic Sclerosis-25 (Revised-CRISS-25) response where Revised-CRISS-25 is a composite endpoint in which a responder is defined as a participant who meets all the following criteria:
研究概览
简要总结
To demonstrate the superiority of anifrolumab to placebo with or without standard therapy on measures of signs, symptoms, and impacts associated with SSc.
研究设计
- 分配方式
- Na
- 主要目的
- Safety Follow up
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Adult patients from 18 to 70 years of age inclusive
- •Stable background therapies can be used including hydroxychloroquine, methotrexate, azathioprine, mycophenolatemofetil, mycophenolic sodium, mycophenolic acid, oralglucocorticoids or tacrolimus
- •Uninvolved skin at injection sites
- •Women of childbearing potential with a negative urine pregnancy test
- •Body weight ≤ 145.0 kg (≤ 319.7 lb)
- •Confirmed classification of SSc according to 2013 (American College of Rheumatology/European League Against Rheumatism(ACR/EULAR)) classification criteria
- •Limited or diffuse cutaneous subsets
- •SSc disease duration ≤ 6 years from first non-Raynaud’s phenomenon manifestation at the time of signing the ICF
- •Either Health Assessment Questionnaire Disability Index (HAQ-DI) score ≥ 0.25 points or Patient Global Assessment (PtGA) score≥ 3 points
- •Modified Rodnan Skin Score (mRSS) > 10 with DiseaseDuration <18 months and/or Diagnosis of ILD by Chest CT
- •If a participant does not meet Inclusion Criterion #7, mRSS ≥15 with disease duration ≥ 18 months and active disease at screening with at least one of the following: -Elevated CRP unrelated to other conditions or ESR -New skin involvement/progression by mRSS score change -presence of at least one tendon friction rub within 3 months of screening
排除标准
- •Anticentromere antibody seropositivity on central laboratory
- •Hematopoietic stem cell transplantation or solid organ/limb transplantation
- •Any severe case of Herpes Zoster (HZ) infection as defined by the protocol
- •Known malignancy or a history of malignancy within 5 years, with exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
- •Major surgery within 8 weeks prior to and/or during study enrollment
- •Known active current or history of recurrent infections
- •Any condition that, in the opinion of the investigator or AstraZeneca, would interfere with efficacy or safety evaluation of the study intervention or put participant at safety risk
- •Severe cardiopulmonary disease as defined by the protocol
- •History of systemic sclerosis renal crisis within past 12 months [Estimated glomerular filtration rate (eGFR) < 45mL/min.]
- •Overlap syndromes, Systemic lupus erythematosus(SLE) with anti-dsDNA antibody seropositivity or Anti-citrullinated protein antibodies-positive (ACPA-positive) rheumatoid arthritis, or SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
- •History of, or current, any other inflammatory diseases, eg, inflammatory bowel disease, skin disease, that, in the opinion of the investigator, could interfere with efficacy and safety assessments or require immunomodulatory therapy
- •Evidence of moderately severe concurrent nervous system, renal, endocrine, hepatic (eg, underlying chronic liver disease [Child Pugh A, B, C hepatic impairment]), or gastrointestinal disease (eg, clinical signs of malabsorption or needing parenteral nutrition) not related to SSc, as determined by the investigator.
研究组 & 干预措施
Anifrolumab Placebo
干预措施: Anifrolumab Placebo (Drug)
Anifrolumab, ANIFROLUMAB
干预措施: Anifrolumab (Drug)
Anifrolumab, ANIFROLUMAB
干预措施: ANIFROLUMAB (Drug)
结局指标
主要结局
Proportion achieving Revised Composite Response Index in Systemic Sclerosis-25 (Revised-CRISS-25) response where Revised-CRISS-25 is a composite endpoint in which a responder is defined as a participant who meets all the following criteria:
Proportion achieving Revised Composite Response Index in Systemic Sclerosis-25 (Revised-CRISS-25) response where Revised-CRISS-25 is a composite endpoint in which a responder is defined as a participant who meets all the following criteria:
Improvement in at least 2 components [≥ 5% increase for Percent predicted forced vital capacity (ppFVC) and/or≥ 25% decrease for mRSS, HAQ-DI, PtGA, Clinician Global Assessment (CGA)
Improvement in at least 2 components [≥ 5% increase for Percent predicted forced vital capacity (ppFVC) and/or≥ 25% decrease for mRSS, HAQ-DI, PtGA, Clinician Global Assessment (CGA)
Worsening in no more than one component (≥ 5% decrease for ppFVC and/or ≥ 25% increase for mRSS, HAQ-DI, PtGA, CGA)
Worsening in no more than one component (≥ 5% decrease for ppFVC and/or ≥ 25% increase for mRSS, HAQ-DI, PtGA, CGA)
No significant SSc-related event as defined in Step 1 (Khanna et al 2021)
No significant SSc-related event as defined in Step 1 (Khanna et al 2021)
Otherwise, a participant is a non-responder
Otherwise, a participant is a non-responder
次要结局
- Treatment related difference in proportion achieving Revised-CRISS-25 components
- Treatment related difference in proportion achieving interstitial lung disease progression
- Treatment related difference in mean change from baseline in mRSS
- Treatment related difference in patient reported outcomes based on the Scleroderma Skin patient reported outcome
- Treatment related difference in mean change from baseline in pulmonary function
- Evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of subcutaneous Anifrolumab
- Treatment related difference in safety and tolerability with or without standard therapy in participants with SSc
- Long term treatment related difference in safety and tolerability with or without standard therapy in participants with SSc
研究者
AstraZeneca Clinical Study Information Center
Scientific
Astrazeneca AB