A Phase 1b, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-007, an Allogeneic Anti-CD19 Chimeric Antigen Receptor Natural Killer Cell (CD19 CAR-NK) Therapy, in Adult Subjects With Refractory Lupus Nephritis or Refractory Systemic Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The main aim of the trial is to learn how well adults with refractory lupus nephritis (LN) or refractory systemic sclerosis (SSc) tolerate TAK-007 and to check for side effects (adverse events).
Other aims are to learn how effective treatment with TAK-007 is in adults with refractory LN or refractory SSc, what effects TAK-007 has on the human body, and whether participants will produce antibodies against TAK-007.
详细描述
The drug being tested in this trial is called TAK-007. TAK-007 is being tested to treat people with refractory LN or refractory SSc. This trial will look at the safety and tolerability of TAK-007.
The trial will enroll approximately 26 participants. Participants will receive a single dose or multiple doses of TAK-007, which is an anti-CD19 chimeric antigen receptor natural killer cell (CD19 CAR-NK) therapy.
Participants with refractory LN will be treated with 3 days of intravenous (IV) lymphodepleting chemotherapy (LDC) and then after a gap of at least 2 days, a single IV dose of TAK-007 on Day 1. For participants with refractory SSc the trial has 2 parts. In Part 1, participants with refractory SSc will be treated with 3 days of IV LDC and then after a gap of at least 2 days, a single IV dose (Part 1a - single dose) or three IV doses (Part 1b - multiple doses) of TAK-007. Based on the data of Part 1, Part 2 (expansion) may be initiated in participants with refractory SSc to further evaluate the impact of LDC followed by single dose or multiple doses of TAK-007.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10^6 TAK-007 on Day 1.
干预措施: Chemotherapy Agents (Drug)
LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with LN will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10^6 TAK-007 on Day 1 with a potential to explore an alternate dose level if deemed appropriate.
干预措施: TAK-007 (Biological)
LN Cohort: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with LN will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10^6 TAK-007 on Day 1 with a potential to explore an alternate dose level if deemed appropriate.
干预措施: Chemotherapy Agents (Drug)
SSc Cohort: Part 1a: Single Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by a single dose of IV 800 × 10^6 TAK-007 on Day 1.
干预措施: TAK-007 (Biological)
SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15.
干预措施: TAK-007 (Biological)
SSc Cohort: Part 1b: Multiple Dose TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Participants with SSc will receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15.
干预措施: Chemotherapy Agents (Drug)
SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Based on the data of Part 1, Part 2 may be initiated for participants with SSc to receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by either single dose of IV 800 × 10^6 TAK-007 on Day 1 or multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15.
干预措施: TAK-007 (Biological)
SSc Cohort: Part 2 (Dose Expansion): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
Based on the data of Part 1, Part 2 may be initiated for participants with SSc to receive IV LDC, for 3 days in conditioning phase (Days -5, -4, and -3), followed by either single dose of IV 800 × 10^6 TAK-007 on Day 1 or multiple doses of IV 800 × 10^6 TAK-007 on Days 1, 8, and 15.
干预措施: Chemotherapy Agents (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Up to Day 30
DLTs are defined as any event throughout the study meeting the protocol-defined criteria that occur by Day 30 after administration of TAK-007 infusion on Day 1.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose of LDC up to end of study (EOS) [up to Month 24]
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. TEAEs are defined as any AE that begins on or after the start date of LDC.
次要结局
- Change From Baseline in Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL) on High-Resolution Computed Tomography (HRCT) Scan of the Thorax in Participants With Refractory SSc(Baseline up to Month 24)
- Cmax: Maximum Observed Plasma Concentration for TAK-007(Pre-dose and at multiple time points post-dose up to Month 24)
- Tmax: Time to Reach the Cmax for TAK-007(Pre-dose and at multiple time points post-dose up to Month 24)
- Tlast: Time of Last Measurable Concentration Above the Lower Limit of Quantitation for TAK-007(Pre-dose and at multiple time points post-dose up to Month 24)
- Change From Baseline in CD19+ B Cell Counts(Baseline up to Month 24)
- Change From Baseline in Plasma Cytokine Levels(Baseline up to Month 3)
- Change From Baseline in Clinician's Global Assessment (CGA) Score(Baseline up to Month 24)
- Percentage of Participants With Antidrug Antibodies Categorized as Anti-Human Leukocyte Antigen (HLA) and Anti- Chimeric Antigen Receptor (CAR)(Up to Month 24)
- Duration of CRR in Participants With Refractory LN(Up to Month 24)
- Time to DORIS Remission in Participants With Refractory LN(Up to Month 24)
- Duration of DORIS Remission in Participants With Refractory LN(Up to Month 24)
- Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels in Participants With Refractory LN(Baseline up to Month 24)
- AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-007(Pre-dose and at multiple time points post-dose up to Month 24)
- Percentage of Participants With Replication Competent Retrovirus (RCR) in Blood(Up to Month 24)
- Change From Baseline in Adjusted Carbon Monoxide Diffusing Capacity (DLCO) % Predicted in Participants With Refractory SSc(Baseline up to Month 24)
- Change From Baseline in Patient Global Assessment (PtGA) in Participants With Refractory SSc(Baseline up to Month 24)
- Percentage of Participants With Refractory LN Achieving a Reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Relative to Baseline(Baseline through Month 24)
- Percentage of Participants With Refractory LN Achieving Complete Renal Response (CRR)(Up to Month 24)
- Time to CRR in Participants With Refractory LN(Up to Month 24)
- Time to LLDAS in Participants With Refractory LN(Up to Month 24)
- Duration of LLDAS in Participants With Refractory LN(Up to Month 24)
- Change From Baseline in Antinuclear Antibody (ANA) Levels in Participants With Refractory LN(Baseline up to Month 24)
- Change From Baseline in Serum Creatinine Levels in Participants With Refractory LN(Baseline up to Month 24)
- Change From Baseline in eGFR in Participants With Refractory LN(Baseline up to Month 24)
- Change From Baseline in Complement (C3, C4) Levels in Participants With Refractory LN(Baseline up to Month 24)
- Percentage of Participants With Refractory LN Achieving Lupus Low Disease Activity State (LLDAS)(Up to Month 24)
- Percentage of Participants With Refractory LN Meeting the Definition of Remission in Systemic Lupus Erythematosus (DORIS) Criteria(Up to Month 24)
- Change From Baseline in Proteinuria Levels in Participants With Refractory LN(Baseline up to Month 24)
- Change From Baseline in Forced Vital Capacity (FVC) in Participants With Refractory SSc(Baseline up to Month 24)
- Change From Baseline in Percentage (%) Predicted Forced Vital Capacity (ppFVC) in Participants With Refractory SSc(Baseline up to Month 24)
- Percentage of Refractory SSc Participants With no Worsening of Pulmonary Function(Up to Month 24)
- Change From Baseline in Modified Rodnan Skin Score (mRSS) in Participants With Refractory SSc(Baseline up to Month 24)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) in Participants With Refractory SSc(Baseline up to Month 24)
- Percentage of Participants Achieving Revised Composite Response Index in Systemic Sclerosis (R-CRISS) Response(Up to Month 24)