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

Description

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)/ lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), and diffuse cutaneous systemic sclerosis (DcSSc).

Trial Eligibility

Inclusion Criteria: General Inclusion Criteria: 1. 17 years of age and older. 2. Participants must have adequate organ function as defined in the protocol. SLE/LN-specific Inclusion Criteria: 1. 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. 2. Participants must have current or history of elevated anti-double stranded deoxyribonucleic acid (anti-dsDNA) and/or elevated anti-Smith antibody test. 3. Participants with diabetes or hypothyroidism should have well-controlled disease, with stable medications for at least 4 weeks prior to Screening. SLE-specific Inclusion Criteria: 1. Participants who have: 1. 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 2. 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 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. For participants with Dermatomyositis (DM) or Polymyositis (PM): 1. Meet 2017 American College of Rheumatology (ACR)/ European Alliance of Associations for Rheumatology (EULAR) diagnostic criteria for definite or probable DM or PM. 2. If PM, have at least one myositis-specific antibody (MSA) at Screening or muscle biopsy available for review. 2. For participants with anti-synthetase syndrome (ASyS), have a diagnosis of ASyS, with elevated transfer ribonucleic acid (tRNA) synthetase autoantibodies at screening. 3. Have active IIM at screening: 1. For DM, activity is defined as having at least 3 criteria from the CSM including Manual Muscle Testing (MMT-8) score \<142/150 criteria and agreement by the Adjudication Committee; or, if MMT criteria are not met, all of the following must be present: i. A cutaneous visual analogue score (VAS) score of \>3 cm on a 10 cm VAS scale: MDAAT, and ii. Elevation of at least one muscle enzyme (creatine kinase \[CK\]; aldolase; lactate dehydrogenase \[LDH\]; alanine aminotransferase \[ALT\]; or aspartate aminotransferase \[AST\]) to a minimum level of 1.3 X upper limit of normal (ULN), and iii. 1 additional core set measure. 2. For PM, activity is based on elevated muscle enzymes and/or typical findings on magnetic resonance imaging (MRI) and agreement by the Adjudication Committee. 3. For ASyS, activity is defined based on the involved organ and will be assessed by the Adjudication Committee. DcSSc-specific Inclusion Criteria: 1. Meets the 2013 ACR/EULAR criteria for SSc with a total score of ≥9. 2. Meets criteria for DcSSc, including skin involvement proximal to the elbow and/or knee. 3. mRSS units ≥15 at Screening; for participants agreeing to biopsy, skin thickening from SSc in the forearm suitable for biopsy. Exclusion Criteria: General Exclusion Criteria: 1. Participants on hemodialysis. 2. Other comorbid conditions as defined in the protocol. 3. History of bone marrow/hematopoietic stem cell or solid organ transplant. 4. 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. 5. Thromboembolic events within last 12 months. 6. Participants with severe hepatic dysfunction, defined as grade C-Child-Pugh. SLE-specific Exclusion Criteria: 1. Participants with BILAG A for neuropsychiatric SLE. 2. Any current, acute, and severe lupus-related flare that needs immediate treatment. 3. Drug-induced SLE rather than idiopathic SLE. 4. 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. 5. Participants with a urinary protein creatinine ratio (UPCR) of \>3 grams per gram (g/g). 6. Participants with estimated glomerular filtration rate \<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: 1. Participants with BILAG A for neuropsychiatric SLE. 2. Any current, acute, and severe lupus-related flare that needs immediate treatment. 3. Drug-induced SLE rather than idiopathic SLE. 4. Participants with predominantly LN Class V, or Class VI on the most recent biopsy according to the 2018 revised ISN/RPS criteria. 5. 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: 1. 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. 2. Have severe muscle damage as defined in the protocol. 3. Participants with ILD will be excluded if there is severe end stage lung disease as defined in the protocol. DcSSc-specific Exclusion Criteria 1. 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. 2. Participants with ILD will be excluded if there is severe end stage lung disease as defined in the protocol.

Study Info

Interventions

Locations Recruiting

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