A Phase 1 Open-label, Multiregional, Multicenter, Basket Study Evaluating the Safety and Efficacy of KITE-363, an Autologous Anti-CD19/CD20 CAR T-cell Therapy in Participants With Refractory Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 52
- 试验地点
- 11
- 主要终点
- Phase 1b: Systemic Sclerosis (SSc) Cohort: Proportion of Participants With Improvement in Disease Activity by the Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) at Month 6
研究概览
简要总结
This study will have two Phases: Phase 1a and Phase 1b. The goal of this clinical study is to learn more about the study drug KITE-363, to establish dosing, tolerability, safety, and preliminary efficacy of KITE-363 in participants with refractory autoimmune diseases.
The primary objectives of this study are:
Phase 1a: To evaluate the safety and tolerability of KITE-363 in participants with autoimmune disease. To determine the recommended dose for Phase 1b.
Phase 1b: To evaluate the safety and efficacy of KITE-363 in participants with autoimmune disease.
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
- •Inclusion Criteria for systemic lupus erythematosus (SLE) and lupus nephritis (LN):
- •Age ≥ 18 years
- •Meet the European Alliance of Associations for Rheumatology (EULAR)- American College of Rheumatology (ACR) 2019 classification criteria for SLE
- •Presence of either double-stranded deoxyribonucleic acid (DNA) anti- double-stranded DNA (anti-dsDNA) and/or anti-Smith antibodies at screening per local laboratory.
- •Moderate to severe, active disease defined as at least one British Isles Lupus Assessment Group (BILAG-A) score or 2 BILAG B (excluding constitutional and/or neuropsychiatric organ system).
- •Refractory to steroids and inadequate response or intolerance to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, anifrolumab, rituximab, obinutuzumab, methotrexate, azathioprine, cyclosporin, tacrolimus, or voclosporin.
- •For LN: Refractory to steroids and inadequate response or intolerance to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, rituximab, obinutuzumab, azathioprine, cyclosporin, tacrolimus, or voclosporin
- •Inclusion Criteria for LN:
- •Renal biopsy-proven Class III or intravenous (IV) ± V LN according to the revised International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria within 6 months prior to or during screening
- •Evidence of active LN at screening
- •Inclusion Criteria for systemic sclerosis (SSc):
- •Age ≥ 18 years
- •Diffuse Systemic Sclerosis (SSc) according to ACR/EULAR 2013 classification criteria with active skin disease and/or progressive SSc-interstitial lung disease (ILD) OR limited SSc with progressive ILD.
- •Refractory or intolerance to 1 of the following for a minimum of 3 months and/or contraindication: mycophenolate mofetil or its derivatives, methotrexate, tocilizumab (or other IL-6 inhibitor), rituximab (or other B-cell depleting agent), nintedanib (or other antifibrotic agents), cyclophosphamide.
- •High-resolution computer tomography (HRCT) scan and pulmonary function test (PFT) within 3 months prior to screening.
- •Inclusion Criteria for idiopathic inflammatory myopathy (IIM):
- •Age ≥ 18 years
- •Probable or definite IIM based on EULAR/ACR 2017 classification (excluding inclusion body myositis).
- •Active disease demonstrated by electromyography (EMG), magnetic resonance imaging (MRI) or muscle enzymes
- •Moderate to severe disease activity
- •Positive for myositis specific antibodies for patients with non-dermatomyostitis IIM
- •HRCT scan and PFT within 3 months prior to screening.
- •Refractory or intolerance to at least 1 month of glucocorticoids and standardized use of at least 2 immunosuppressant/modulator (eg, intravenous gamma globulins, methotrexate, mycophenolate mofetil and its derivatives, azathioprine, cyclophosphamide, calcineurin inhibitors, Janus kinase (JAK) inhibitors, rituximab or other B-cell depleting agent).
- •Inclusion Criteria for all Cohorts:
- •Adequate hepatic, renal, pulmonary, and cardiac function.
排除标准
- •Exclusion Criteria for all Cohorts:
- •Females of childbearing potential who are pregnant or breast feeding.
- •Dialysis within the past year.
- •History of malignancy, within the last 5 years.
- •Hypogammaglobulinemia requiring immunoglobulin replacement.
- •History of autologous or allogeneic stem cell transplant and/or organ transplant.
- •Prior treatment with cellular therapy, gene therapy and/or T-cell engager therapy.
- •Known history of HIV infection, or hepatitis B or C virus infections.
- •Active or untreated latent tuberculosis (TB).
- •Active or uncontrolled infections.
- •Nonspecific, overlap, mixed autoimmune diseases not clearly identified into any of the studied cohorts.
- •Exclusion Criteria for LN:
- •Significant pre-existing damage or rapidly progressive glomerulonephritis (GN).
- •Exclusion Criteria for SLE:
- •Drug-induced SLE.
- •Catastrophic antiphospholipid syndrome.
- •Thrombotic thrombocytopenic purpura.
- •Active or unstable lupus neuropsychiatric manifestations within last 6 months.
- •Exclusion Criteria for SSc:
- •Infected digital ulceration or necrosis with signs of infection.
- •Severe pulmonary hypertension.
- •History of systemic sclerosis renal crisis within 12 months prior to enrollment.
- •History of active bleeding related to gastric antral vascular ectasia.
- •Exclusion Criteria for IIM:
- •Other inflammatory and noninflammatory myopathies.
- •Severe, irreversible muscle damage.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
干预措施: Fludarabine (Drug)
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
干预措施: KITE-363 (Biological)
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.
干预措施: KITE-363 (Biological)
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
干预措施: Cyclophosphamide (Drug)
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.
干预措施: Cyclophosphamide (Drug)
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Phase 1b: Systemic Sclerosis (SSc) Cohort: Proportion of Participants With Improvement in Disease Activity by the Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) at Month 6
时间窗: Month 6
Phase 1b: Systemic lupus erythematosus (SLE): Proportion of participants meeting DORIS remission and Lupus low Disease Activity State (LLDAS) criteria at Month 6
时间窗: Month 6
Phase 1b: Lupus Nephritis (LN): Proportion of Participants Meeting DORIS Remission
时间窗: Month 6
Phase 1b: LN: Proportion of Participants Achieving a Complete Renal Response at Month 6
时间窗: Month 6
Phase 1b: Idiopathic Inflammatory Myopathy (IIM): Proportions of Participants Meeting European League Against Rheumatism (EULAR)-American College of Rheumatology (ACR) Moderate and Major response 2016 Criteria in Total Improvement Score (TIS) at Month 6
时间窗: Month 6
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363
时间窗: Up to 2 years
Phase 1b: All Cohorts Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs)
时间窗: Up to 2 years
次要结局
- Characterization of Product, Including T-cell Phenotype as Assessed by Percent Change From Baseline in cluster of differentiation 3 (CD3)+ Cells and T Cells(Baseline up to 2 years)
- Pharmacokinetic parameter: Serum Concentration of KITE-363 CAR T-cells(Up to 2 years)
- Pharmacokinetic parameter: Peak Concentration (Cmax) for KITE-363 CAR T-cells(Up to 2 years)
- Pharmacokinetic parameter: AUC for KITE-363 CAR T-cells(Up to 2 years)
- Pharmacokinetic parameter: Time to Peak Serum Concentration (Tmax) for KITE-363 CAR T-cells(Up to 2 years)
- Pharmacodynamic Parameters: Serum Concentration of Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors in blood over time(Up to 2 years)
- Pharmacodynamic Parameters: Peak Serum Concentration (Cmax) for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors(Up to 2 years)
- Pharmacodynamic Parameters: AUC for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors(Up to 2 years)
- Pharmacodynamic Parameters: Time to Peak Serum Concentration (Tmax) for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors(Up to 2 years)
- Percentage of Participants with Antibodies Against KITE-363 CAR T cells(Up to 2 years)
- Change from Baseline in Levels of B cells(Up to 2 years)