A Study of CNTY-101 in Participants With Refractory B Cell-mediated Autoimmune Diseases (CALiPSO-1)

Century Therapeutics

Status and phase: Enrolling; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06255028

CNTY-101-151-01

2024-518797-13 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 48 estimated patients

Sex: All

Ages: 17+ years old

Volunteers: No Healthy Volunteers

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:

2. 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

3. 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):

2. For Dermatomyositis (DM), meet 2017 American College of Rheumatology/European Alliance of Associations of Rheumatology (ACR/EULAR) diagnostic criteria for definite or probable DM.

3. 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.

4. 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 Exclusion Criteria:

1. Participants on hemodialysis.
2. Other comorbid conditions as defined in the protocol.
3. 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.
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 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:

1. Participants with BILAG A for neuropsychiatric SLE.
2. 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.
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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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48 participants in 4 patient groups

Arm A: CNTY-101 in SLE Participants

Experimental group

Description:

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.

Treatment:

Drug: Lymphodepleting Chemotherapy

Biological: CNTY-101

Biological: IL-2

Arm B: CNTY-101 in LN Participants

Experimental group

Description:

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.

Treatment:

Drug: Lymphodepleting Chemotherapy

Biological: CNTY-101

Biological: IL-2

Arm C: CNTY-101 in IIM Participants

Experimental group

Description:

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.

Treatment:

Drug: Lymphodepleting Chemotherapy

Biological: CNTY-101

Biological: IL-2

Arm D: CNTY-101 in DcSSC Participants

Experimental group

Description:

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.

Treatment:

Drug: Lymphodepleting Chemotherapy

Biological: CNTY-101

Biological: IL-2