The CALiPSO-1 Study: A Study of CNTY-101, a CD19-targeted CAR iNK Cell Product, in Participants With Refractory B Cell-mediated Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs
研究概览
简要总结
CALiPSO-1 is a Phase 1, multi-centre, dose-confirmation study to evaluate the safety and efficacy of CNTY-101 in participants with refractory B cell-mediated autoimmune diseases including those with moderate to severe systemic lupus erythematosus (SLE) with or without lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), and diffuse cutaneous systemic sclerosis (DcSSc).
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
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General Inclusion Criteria:
- •17 years of age and older.
- •Participants must have adequate organ function as defined in the protocol.
- •SLE/LN-specific Inclusion Criteria:
- •Participants must have a diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus for at least 6 months.
- •Participants must have current or history of elevated anti-double stranded deoxyribonucleic acid (anti-dsDNA), anti-Smith, anti-histone, and/or anti-nucleosome antibodies.
- •SLE-specific Inclusion Criteria:
- •1. Participants who have:
- •A Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥8 (including at least 4 points from non-laboratory assessments; excluding alopecia, mucosal ulcers, and fever) and at least 2 British Isles Lupus Assessment Group B (BILAG B) organ system scores and/or
- •At least one British Isles Lupus Assessment Group A (BILAG A) organ system score, including cardiac (peri- or myocarditis), respiratory (pleuritis or lung involvement), vascular and renal.
- •LN-specific Inclusion Criteria:
- •1. Participants with active, biopsy-proven, proliferative LN Class III or IV, either with or without the presence of class V, according to the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria. Biopsy must be within 12 months prior to Screening or during Screening.
- •IIM-specific Inclusion Criteria:
- •1. Classification of IIM (juvenile-onset IIM may be included):
- •For Dermatomyositis (DM), meet 2017 American College of Rheumatology/European Alliance of Associations of Rheumatology (ACR/EULAR) diagnostic criteria for definite or probable DM.
- •For participants with anti-synthetase syndrome (ASyS), meet Classification Criteria for anti-synthetase syndrome per the Classification Criteria for Anti-Synthetase Syndrome (CLASS) Project with a positive tRNA synthetase autoantibody at Screening or per medical history.
- •For Polymyositis (PM)/ necrotizing myopathy (NM), meet 2017 ACR/ EULAR classification criteria for definite or probable PM/NM and meet one of the following criteria:
- •i. Positive myositis specific antibody (MSA) at Screening or per medical history or ii. Muscle biopsy at Screening or per medical history available for review
- •DcSSc-specific Inclusion Criteria:
- •Meets the 2013 ACR/EULAR criteria for SSc with a total score of ≥
- •Meets criteria for DcSSc, including skin involvement proximal to the elbow and/or knee.
- •mRSS units ≥15 at Screening; for participants agreeing to biopsy, skin thickening from SSc in the forearm suitable for biopsy.
排除标准
- •General Exclusion Criteria:
- •Participants on hemodialysis.
- •Other comorbid conditions as defined in the protocol.
- •History of allogeneic bone marrow/hematopoietic stem cell or solid organ transplant at any time. History of autologous stem cell transplant >100 days prior to Screening is allowed.
- •Recent or clinically significant central nervous system (CNS) disease, including but not limited to cerebrovascular accident, epilepsy, severe brain injury, dementia, Parkinson's disease, cerebellar disease, seizures, organic brain syndrome, lupus headache, or psychosis at any time prior to study.
- •Thromboembolic events within last 12 months.
- •Participants with severe hepatic dysfunction, defined as grade C-Child-Pugh.
- •SLE-specific Exclusion Criteria:
- •Participants with BILAG A for neuropsychiatric SLE.
- •Any current, acute, and severe lupus-related flare that needs immediate treatment.
- •Drug-induced SLE rather than idiopathic SLE.
- •Participants with a diagnosis of LN Classes III, IV, V, or VI on the most current biopsy according to the 2018 revised ISN/RPS criteria.
- •Participants with estimated glomerular filtration rate (eGFR) <45 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (measured by Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) or serum creatinine >2.5 milligrams per deciliter (mg/dL).
- •LN-specific Exclusion Criteria:
- •Participants with BILAG A for neuropsychiatric SLE.
- •Any severe lupus-related flare such as acute CNS lupus (eg, psychosis, seizure), catastrophic antiphospholipid syndrome, or rapidly progressive glomerulonephritis that, in the opinion of the Investigator, would cause an unacceptable safety risk.
- •Drug-induced SLE rather than idiopathic SLE.
- •Participants with predominantly LN Class V, or Class VI on the most recent biopsy according to the 2018 revised ISN/RPS criteria.
- •Participants with estimated glomerular filtration rate <30 mL/min/1.73 m^2 (measured by Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) or serum creatinine >2.5 mg/dL.
- •IIM- specific Exclusion Criteria:
- •Participants on hemodialysis or estimated glomerular filtration rate <45 mL/min/1.73 m^2 (measured by Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) or serum creatinine >2.5 mg/dL.
- •Have severe muscle damage as defined in the protocol.
- •Participants with ILD will be excluded if there is severe end stage lung disease as defined in the protocol.
- •DcSSc-specific Exclusion Criteria
- •Participants on hemodialysis or estimated glomerular filtration rate <45 mL/min/1.73 m^2 (measured by Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) or serum creatinine >2.5 mg/dL.
- •Participants with ILD will be excluded if there is severe end stage lung disease as defined in the protocol.
研究组 & 干预措施
Arm A: CNTY-101 in SLE Participants
During Part 1 (Dose Confirmation Phase), participants with SLE will undergo lymphodepleting chemotherapy (LDC) followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental human recombinant interleukin 2 (IL-2).
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.
干预措施: CNTY-101 (Biological)
Arm A: CNTY-101 in SLE Participants
During Part 1 (Dose Confirmation Phase), participants with SLE will undergo lymphodepleting chemotherapy (LDC) followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental human recombinant interleukin 2 (IL-2).
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.
干预措施: IL-2 (Biological)
Arm A: CNTY-101 in SLE Participants
During Part 1 (Dose Confirmation Phase), participants with SLE will undergo lymphodepleting chemotherapy (LDC) followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental human recombinant interleukin 2 (IL-2).
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.
干预措施: Lymphodepleting Chemotherapy (Drug)
Arm B: CNTY-101 in LN Participants
During Part 1 (Dose Confirmation Phase), participants with LN will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: CNTY-101 (Biological)
Arm B: CNTY-101 in LN Participants
During Part 1 (Dose Confirmation Phase), participants with LN will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: IL-2 (Biological)
Arm B: CNTY-101 in LN Participants
During Part 1 (Dose Confirmation Phase), participants with LN will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: Lymphodepleting Chemotherapy (Drug)
Arm C: CNTY-101 in IIM Participants
During Part 1 (Dose Confirmation Phase), participants with IIM will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: CNTY-101 (Biological)
Arm C: CNTY-101 in IIM Participants
During Part 1 (Dose Confirmation Phase), participants with IIM will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: IL-2 (Biological)
Arm C: CNTY-101 in IIM Participants
During Part 1 (Dose Confirmation Phase), participants with IIM will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: Lymphodepleting Chemotherapy (Drug)
Arm D: CNTY-101 in DcSSC Participants
During Part 1 (Dose Confirmation Phase), participants with DcSSC will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: CNTY-101 (Biological)
Arm D: CNTY-101 in DcSSC Participants
During Part 1 (Dose Confirmation Phase), participants with DcSSC will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: IL-2 (Biological)
Arm D: CNTY-101 in DcSSC Participants
During Part 1 (Dose Confirmation Phase), participants with DcSSC will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.
After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.
During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.
干预措施: Lymphodepleting Chemotherapy (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs
时间窗: Up to 29 days
Percentage of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days after first CNTY-101 infusion
Recommended Phase 2 Regimen (RP2R) of CNTY-101 With/Without IL-2 (With or Without Optimized LDC)
时间窗: Up to 3 months after the first CNTY-101 infusion
次要结局
- Percentage of Participants With TEAEs and Serious Adverse Events (SAEs)(Day 1 up to 1 year)
- Percentage of Participants With Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Severity of CRS and ICANS(Day 1 up to 1 year)
- Percentage of Participants With Clinically Significant Laboratory Abnormalities and Severity of Laboratory Abnormalities(Day 1 up to 1 year)
- Percentage of Participants With SLE - Responder Index 4 (SRI-4) Response(Up to 1 year)
- Percentage of Participants With Low Disease Activity by Lupus Low Disease Activity State (LLDAS)(Up to 1 year)
- Percentage of Participants in Remission as Measured by Definitions of Remission in SLE (DORIS) Remission(Up to 1 year)
- Percentage of Participants With Total Improvement Score (TIS) ≥20, ≥40, and ≥60(Up to 1 year)
- Mean TIS(Baseline up to 1 year)
- Change From Baseline in Each Core Set Measures (CSM)(Baseline up to 1 year)
- Change From Baseline in CSM Component of Manual Muscle Testing (MMT)-8 Score(Baseline up to 1 year)
- Change From Baseline in CSM Component of Patient Global Assessment (PtGA)(Baseline up to 1 year)
- Change From Baseline in CSM Component of Physician Global Assessment (PhGA)(Baseline up to 1 year)
- Change From Baseline in CSM Component of Muscle Enzyme Levels(Baseline up to 1 year)
- Change From Baseline in CSM Component of Health Assessment Questionnaire- Disability Index (HAQ-DI) Score(Baseline up to 1 year)
- Change From Baseline in CSM Component of Extramuscular Assessment by Myositis Disease Activity Assessment Tool (MDAAT)(Baseline up to 1 year)
- For Participants With Interstitial Lung Disease (ILD): Time to Improvement in Forced Vital Capacity (FVC%) ≥10%(Up to 1 year)
- For Participants With ILD: Percentage of Participants With Improvement in FVC% ≥10%(Up to 1 year)
- For Participants with ILD: Change From Baseline in Percent FVC (%FVC)(Baseline up to 1 year)
- For Participants With ILD: Change From Baseline in Percent Diffusion Capacity of The Lung for Carbon Monoxide (%DLCO)(Baseline up to 1 year)
- For Participants With ILD: Time to Progression in Interstitial Lung Disease (ILD)(Up to 1 year)
- For Participants With ILD: Percentage of Participants With Progression in ILD(Up to 1 year)
- For Participants With ILD: Change in Participant Reported Dyspnea Over Time as Measured by University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)(Up to 1 year)
- Change in American College of Rheumatology Combined Response in Diffuse Cutaneous Systemic Sclerosis (ACR-CRISS) Scores(Up to 1 year)
- Percentage of Responders as Measured by ACR-CRISS Score(Up to 1 year)
- Change From Baseline in ACR-CRISS Scores(Baseline up to 1 year)
- Change From Baseline in Fibrosing Skin Disease Based on Modified Rodnan Skin Score (mRSS)(Baseline up to 1 year)
- Change From Baseline in Scleroderma Health Assessment Questionnaire (SHAQ)(Baseline up to 1 year)
研究者
Century Therapeutics Clinical Team
Scientific
Century Therapeutics Inc.