A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of TAK-079 in Combination With Standard Background Therapy in Patients With Moderate to Severe Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 19
- 主要终点
- Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of TAK-079 in comparison with matching placebo, administered once every 3 weeks over a 12-week dosing period in participants with active SLE who are receiving stable background therapy for SLE.
详细描述
TAK-079 is being tested in a study population with moderate to severe SLE. This study will evaluate the safety and biologic activity of TAK-079 or matching placebo in combination with stable SLE background therapy.
The study will enroll approximately 24 participants across 3 sequentially enrolling cohorts. Each cohort will enroll 8 participants, where 6 participants will be assigned to TAK-079 injection, and 2 participants will be assigned to Placebo. Participants will receive TAK-079 or matching placebo in combination with principal investigator directed background therapy for SLE.
This multi-center trial will be conducted in the United States. Participants will make multiple visits to the clinic, and will be followed up for the safety assessment for the additional 12 weeks up to Week 24 after receiving their last dose of study drug. Based on the clinical assessments, participants may complete or may advance to long-term safety follow up period for an additional 12-week safety monitoring period up to Week 36.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant been diagnosed with SLE as defined by either the 2012 Systemic Lupus International Collaborating Clinics or the American College of Rheumatology diagnostic criteria.
- •The participant has a systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score greater than or equal to (>=)
- •The participant is positive for anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies and/or anti-extractable nuclear antigens (ENA) antibodies.
排除标准
- •The participant had an opportunistic infection less than or equal to (<=)12 weeks before initial study dosing or is currently undergoing treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria.
- •The participant currently has, or recently had, an acute or chronic infection requiring one or more of the following interventions: Hospitalization <=30 days before the screening visit. - Administered parenteral (IV or intramuscular) antibacterial, antiviral, antifungal, or antiparasitic agents <=30 days before the screening visit.
- •The participant has drug-induced SLE or any other rheumatologic or autoimmune disease (excluding secondary Sjögren syndrome or mixed connective tissue disease).
研究组 & 干预措施
Pooled Placebo
TAK-079 placebo-matching injection, subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks. Placebo data will be pooled across all the dose levels.
干预措施: TAK-079 Placebo (Drug)
TAK-079 45 mg
TAK-079 45 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
干预措施: TAK-079 (Drug)
TAK-079 90 mg
TAK-079 90 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
干预措施: TAK-079 (Drug)
TAK-079 135 mg
TAK-079 135 mg injection subcutaneously, once every 3 weeks in combination with principal investigator-directed background therapy for SLE for up to 12 weeks.
干预措施: TAK-079 (Drug)
结局指标
主要结局
Number of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
时间窗: From the study start to end of the study (up to Week 36)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug. An SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
时间窗: From the study start up to end of the study (up to Week 36)
The severity of TEAEs will be graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 definitions of Grade 1 through Grade 5. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Percentage of Participants With ≥ 1 Adverse Event (AE) Leading to Treatment Discontinuation
时间窗: From the study start up to end of the study (up to Week 36)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
次要结局
- AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079(Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose; Day 22 pre-dose and at multiple time points (up to 108 hours) post-dose; Days 43 and 64 pre-dose and at multiple time points (up to 5 hours) post-dose.)
- Number of Participants With Change From Baseline in Immune Cell Subsets Determined Based on Receptor Occupancy(Baseline up to Day 85 (EOT))
- Number of Participants With Positive Anti-drug Antibodies(Baseline up to Day 85 (EOT))
- Cmax: Maximum Observed Plasma Concentration for TAK-079(Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose; Day 22 pre-dose and at multiple time points (up to 108 hours) post-dose; Days 43 and 64 pre-dose and at multiple time points (up to 5 hours) post-dose)
- Change From Baseline in Cytokines Level(Baseline up to Day 85)
- Number of Participants With Change From Baseline In Immune Cell Subsets(Baseline up to Day 85 (End of Treatment [EOT]))