NCT04033926已完成2 期
A Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Active Polymyositis or Dermatomyositis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Mean Change in the Total Improvement Score (TIS) From Start to End of Zetomipzomib (KZR-616) Treatment Period
研究概览
简要总结
This was a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of treatment with KZR-616 in patients with active polymyositis (PM) or dermatomyositis (DM). Patients were evaluated for eligibility during the Screening Period. Eligible patients were stratified by diagnosis of DM or PM and randomized 1:1 to Arm A or Arm B of the study.
During the 32-week treatment period, patients received study drug subcutaneously (SC) once weekly with 2 treatment periods of 16 weeks each.
This study was conducted on an outpatient basis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients at least 18 years of age
- •Body Mass Index (BMI) of 18 to 40 kg/m^2
- •Diagnosis of probable or definite DM or PM by the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria
- •Must have their data reviewed by an adjudication committee to confirm eligibility unless at least 1 of the following is present:
- •Muscle biopsy with evidence of active myositis within the last 6 months prior to or at Screening
- •Electromyography or magnetic resonance imaging with evidence of active myositis within the last 6 months prior to Screening
- •A creatine kinase (CK) ≥4 × upper limit of normal (ULN).
- •Must have demonstrable muscle weakness as measured by the Manual Muscle Testing-8 muscle Groups (MMT-8) with a score ≥80/150 but ≤136/150 units and any 2 of the following:
- •Physician Global Assessment (MDGA) visual analog scale (VAS) ≥2 cm
- •Patient Global Assessment of Disease Activity (PtGADA) VAS ≥2 cm
- •At least one muscle enzyme laboratory measurement ≥1.3 × ULN
- •Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS ≥1 cm.
- •Documented inadequate response OR have demonstrated documented toxicity or intolerance to prior standard of care therapies
- •Has had age-appropriate cancer screening that is up to date and negative for evidence of malignancy as per local standard of care
排除标准
- •Has significant muscle damage or has a muscle damage VAS score ≥5 cm on the MDI
- •Any other form of myositis or myopathy other than PM or DM
- •Any condition that precludes the ability to quantitate muscle strength
- •Has severe interstitial lung disease or has a pulmonary damage VAS score ≥5 cm on the Myositis Damage Index (MDI)
- •Presence of autoinflammatory disease
- •Use of nonpermitted medications or treatments within the specified washout periods prior to screening
- •Patient has had recent serious or ongoing infection, or risk for serious infection
- •Any of the following laboratory values at Screening:
- •Estimated glomerular filtration rate <45 mL/min
- •Hemoglobin <10 g/dL
- •White blood cell (WBC) count <3.0 × 10^9/L
- •Absolute neutrophil count (ANC) <1.5 × 10^9/L (1500/mm^3)
- •Platelet count <100 × 10^9/L
- •Serum AST or serum ALT >2.5 × ULN (unless considered consistent with muscle origin)
- •Serum alkaline phosphatase >2.5 × ULN
- •Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert's syndrome)
- •Thyroid stimulating hormone outside of the central laboratory normal range
- •Immunoglobulin G (IgG) <500 mg/dL.
- •Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure, or prolonged QT interval
- •Major surgery within 12 weeks before Screening or planned during the study period
- •Clinical evidence of significant unstable or uncontrolled diseases
- •Any active or suspected malignancy, including myeloproliferative or lymphoproliferative disorder, or history of documented malignancy within the last 5 years before Screening or within 3 years of diagnosis of myositis, except appropriately excised and cured cervical carcinoma in situ or basal or squamous cell carcinoma of the skin
研究组 & 干预措施
Arm A
Other
- Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks
- Treatment Period 2: Placebo SC weekly for 16 weeks
干预措施: KZR-616 (Drug)
Arm A
Other
- Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks
- Treatment Period 2: Placebo SC weekly for 16 weeks
干预措施: Placebo (Drug)
Arm B
Other
- Treatment Period 1: Placebo SC weekly for 16 weeks
- Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks
干预措施: KZR-616 (Drug)
Arm B
Other
- Treatment Period 1: Placebo SC weekly for 16 weeks
- Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change in the Total Improvement Score (TIS) From Start to End of Zetomipzomib (KZR-616) Treatment Period
时间窗: 16 weeks in each Treatment Period (32 weeks total)
The primary efficacy endpoint was mean change from start to end of zetomipzomib (KZR-616) Treatment Periods in the Total Improvement Score (TIS), which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. Mean change in TIS was calculated by comparing the Baseline and post Baseline observations for patients in both KZR-616 treatment periods combined. Note: TIS scores for placebo treatment periods are presented in this outcome measure but were not included in the primary outcome measure analysis.
次要结局
- Proportion of Patients With TIS Response(16 weeks in each Treatment Period (32 weeks total))
- Number of Patients Meeting the International Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement (DOI)(16 weeks in each Treatment Period (32 weeks total))
- Mean Percent Change From Baseline From Start to End of Treatment in the IMACS Individual CSAMs(16 weeks in each Treatment Period (32 weeks total))
- PK of Zetomipzomib [KZR-616] (Cmax)(Up to 5 hours)
- Mean Change in CDASI From Start to End of Zetomipzomib (KZR-616) Treatment(16 weeks in each Treatment Period (32 weeks total))
- Mean Change in PP-NRS From Start to End of Zetomipzomib (KZR-616) Treatment(16 weeks in each Treatment Period (32 weeks total))
- PK of Zetomipzomib [KZR-616] (Tmax)(Up to 5 hours)
- PK of Zetomipzomib [KZR-616] (AUC)(Up to 5 hours)
- PK of KZR-59587 (Cmax)(Up to 5 hours)
- PK of KZR-59587 (Tmax)(Up to 5 hours)
- PK of KZR-59587 (AUC)(Up to 5 hours)
研究者
研究点 (1)
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