Systemic Lupus Erythematosus, Lupus Nephritis, Idiopathic Inflammatory Myopathies, Diffuse Cutaneous Systemic Sclerosis
Conditions
Keywords
CAR iNK, CAR NK, Cellular therapy, Systemic Lupus Erythematosus, SLE, Induced pluripotent stem cell (iPSC), Anti-CD19 therapy, CNTY-101, Autoimmune disease, Lupus Nephritis, Lupus, Idiopathic Inflammatory Myopathies, Diffuse Cutaneous Systemic Sclerosis, IIM, DcSSc, Myositis, Polymyositis, Dermatomyositis, Anti-synthetase syndrome, Systemic sclerosis, Sclerosis
Brief summary
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).
Interventions
BIOLOGICALCNTY-101
CNTY-101 cells for intravenous (IV) infusion
BIOLOGICALIL-2
IL-2 subcutaneous (SC) injection
LDC as prespecified in the protocol.
Sponsors
Century Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
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), anti-Smith, anti-histone, and/or anti-nucleosome antibodies. 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, 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): 1. For Dermatomyositis (DM), meet 2017 American College of Rheumatology/European Alliance of Associations of Rheumatology (ACR/EULAR) diagnostic criteria for definite or probable DM. 2. 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. 3. 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: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Severity of TEAEs | Up to 29 days |
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | 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) | Up to 3 months after the first CNTY-101 infusion |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) | Baseline 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 |
| Percentage of Participants With TEAEs and Serious Adverse Events (SAEs) | 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 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 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 |
Countries
United States
Outcome results
None listed