A Study of CNTY-101 in Participants With Refractory B Cell-mediated Autoimmune Diseases

NCT06255028 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CNTY-101-151-012024-518797-13
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

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).

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis; Idiopathic Inflammatory Myopathies; Diffuse Cutaneous Systemic Sclerosis

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (27)

• 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

Study Arms (4)

Arm A: CNTY-101 in SLE Participants

EXPERIMENTAL

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.

Biological: CNTY-101; Biological: IL-2; Drug: Lymphodepleting Chemotherapy

Arm B: CNTY-101 in LN Participants

EXPERIMENTAL

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.

Biological: CNTY-101; Biological: IL-2; Drug: Lymphodepleting Chemotherapy

Arm C: CNTY-101 in IIM Participants

EXPERIMENTAL

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.

Biological: CNTY-101; Biological: IL-2; Drug: Lymphodepleting Chemotherapy

Arm D: CNTY-101 in DcSSC Participants

EXPERIMENTAL

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.

Biological: CNTY-101; Biological: IL-2; Drug: Lymphodepleting Chemotherapy

Interventions

CNTY-101 BIOLOGICAL

CNTY-101 cells for intravenous (IV) infusion

Arm A: CNTY-101 in SLE Participants; Arm B: CNTY-101 in LN Participants; Arm C: CNTY-101 in IIM Participants; Arm D: CNTY-101 in DcSSC Participants

IL-2 BIOLOGICAL

IL-2 subcutaneous (SC) injection

Arm A: CNTY-101 in SLE Participants; Arm B: CNTY-101 in LN Participants; Arm C: CNTY-101 in IIM Participants; Arm D: CNTY-101 in DcSSC Participants

Lymphodepleting Chemotherapy DRUG

LDC as prespecified in the protocol.

Arm A: CNTY-101 in SLE Participants; Arm B: CNTY-101 in LN Participants; Arm C: CNTY-101 in IIM Participants; Arm D: CNTY-101 in DcSSC Participants

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and older.
• Participants must have adequate organ function as defined in the protocol.
• 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.
• \. 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.
• \. 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.
• \. 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
• Meets the 2013 ACR/EULAR criteria for SSc with a total score of ≥9.
• Meets criteria for DcSSc, including skin involvement proximal to the elbow and/or knee.

You may not qualify if:

• 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.
• 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).
• 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.

Sponsors & Collaborators

• Century Therapeutics, Inc.: lead

Study Sites (6)

Keck School of Medicine of University of Southern California

Los Angeles, California, 90033, United States

Location

UC Davis

Sacramento, California, 957817, United States

Location

Lurie Children's; Northwestern Medicine - Northwestern Medical Group

Chicago, Illinois, 60611, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Fred Hutch

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis; Myositis; Scleroderma, Diffuse; Autoimmune Diseases; Polymyositis; Dermatomyositis; Scleroderma, Systemic; Sclerosis

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Skin Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 12, 2024
• Study Start: February 6, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)