A Study of CNTY-101 in Participants With Moderate to Severe Systemic Lupus Erythematosus (SLE) (CALiPSO-1)

The CALiPSO-1 Study: A Study of CNTY-101, a CD19-targeted CAR iNK Cell Product, in Participants With Moderate to Severe Systemic Lupus Erythematosus

CALiPSO-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety and efficacy of CNTY-101 in participants with moderate to severe systemic lupus erythematosus.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: CNTY-101; Drug: Lymphodepleting Chemotherapy; Biological: IL-2

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nikolaus Trede; Phone Number: 8885067670; Email: calipso-1_clinicalteam@centurytx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 elevated anti- double stranded deoxyribonucleic acid (anti-dsDNA) and/or elevated anti-Smith antibody test at Screening (a single retest of previously positive participants who were negative at screening will be allowed).
3. Participants with diabetes or hypothyroidism should have well-controlled disease, with stable medications for at least 4 weeks prior to screening.

4. Participants who despite at least 2 lines of prior standard immunosuppressive therapies for ≥12 weeks 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

Exclusion Criteria:

1. Unable to washout prohibited or maintain stable allowed SLE therapy for 4 weeks prior to LDC therapy.
2. Participants on hemodialysis.
3. Participants with active lupus nephritis (prior history of biopsy-documented International Society of Nephrology/Renal Pathology Society Class VI Lupus Nephritis).
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. Participants with BILAG A for neuropsychiatric SLE.
6. Thromboembolic events within last 12 months.
7. Participants with severe hepatic dysfunction, defined as grade C-Child-Pugh.
8. Diagnosis of drug-induced SLE rather than idiopathic SLE.
9. Participants with either proteinuria >3 grams per day (g/day), or a urinary protein creatinine ratio (UPCR) of >3 grams per gram (g/g). At least 2 measurements of proteinuria or UPCR over the past 6 months is required to confirm control of renal disease.
10. Study participant with chronic kidney failure stage 4, manifested by 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation Phase; Lymphodepleting chemotherapy (LDC) will be 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), administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.	Biological: CNTY-101; CNTY-101 cells for intravenous (IV) infusion; Drug: Lymphodepleting Chemotherapy; LDC as prespecified in the protocol.; Biological: IL-2; IL-2 subcutaneous (SC) injection
Experimental: Part 2: Dose Expansion Phase; Treatment using the recommended phase 2 regimen (RP2R) confirmed during Part 1 of the study.	Biological: CNTY-101; CNTY-101 cells for intravenous (IV) infusion; Drug: Lymphodepleting Chemotherapy; LDC as prespecified in the protocol.; Biological: IL-2; IL-2 subcutaneous (SC) injection

What is the study measuring?

Primary Outcome Measures

Outcome 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) With/Without IL-2	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Century Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Autoimmune disease; Cellular therapy; CNTY-101; CAR NK; CAR iNK; Induced pluripotent stem cell (iPSC); Anti-CD19 therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CNTY-101-151-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No