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NCT06925542PHASE1Recruiting

A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease

CRISPR Therapeutics

Start Date

3/10/2025

Completion Date

12/31/2031

Summary

This is a single-arm, open-label, multicenter, ascending dose Phase 1 study evaluating the safety and preliminary efficacy of CTX112 in adult subjects with refractory autoimmune diseases, including active systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or idiopathic inflammatory myopathy (IIM).

Detailed Description

This study may enroll up to 80 subjects in total. CTX112 is a CD19 directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of refractory autoimmune diseases. The cells are from healthy adult volunteer donors that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).

Eligibility Criteria

Age Range: 18 years to 70 years

Key Inclusion Criteria: 1. Age ≥18 years and \< 70 years of age. 2. Subjects must voluntarily sign a written informed consent and be willing and able to comply with all study requirements. 3. Adequate hematologic, renal, liver, cardiac and pulmonary organ function. 4. Subjects must agree to use acceptable methods of contraception. 5. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures. 6. Diagnosis of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM). For systemic lupus erythematosus (SLE) subjects: \- Diagnosis of SLE by a board-certified rheumatologist that conforms with 2019 ACR/EULAR criteria. For lupus nephritis subjects, active, biopsy-proven proliferative lupus nephritis Class III or IV, either with or without the presence of Class V, and appropriate National Institutes of Health index activity score using the 2018 International Society of Nephrology/Renal Pathology Society criteria. For Systemic Sclerosis (SSc) subjects: \- Diagnosis of diffuse cutaneous systemic sclerosis (dcSSC) or SSc-ILD that conforms with 2013 ACR/EULAR criteria. Subjects should meet active skin or lung disease criteria. For Idiopathic Inflammatory Myopathy (IIM) subjects: \- Diagnosis with dermatomyositis (DM), polymyositis (PM) or myositis as part of rheumatologic overlap syndrome, antisynthetase (ASyS), or immune-mediated necrotizing myopathy (IMNM) that conforms with 2017 ACR/EULAR criteria for inflammatory myopathies. Subjects must meet moderate severe, skin, or lung involvement criteria. Key Exclusion Criteria: 1. Prior anti-CD19 therapy or any gene therapy/genetically modified cell therapy. 2. Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant. 3. Severe active or history of central nervous (CNS) involvement. 4. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease with CNS involvement other than SLE, SSc or IIM. 5. Mixed connective tissue disease with no clear predominant disease. 6. Presence of study disease manifestations or other conditions that are likely to pose increase safety risks and/or confound disease assessments, or pose significant risk to those receiving CAR T cell therapy. 7. History of primary or secondary immunodeficiency. 8. Presence or history of certain bacterial, viral or fungal infection. 9. Malignancy in the last 5 years (with the exception of cancers deemed to be low likelihood for recurrence). 10. Diagnosis of a genetic disorder associated with bone marrow failure or myelodysplastic syndrome. 11. History or current diagnosis of catastrophic anti-phospholipid syndrome or anti phospholipid syndrome that requires ongoing anticoagulation. 12. Pregnant or lactating. 13. Presence or history of disease requiring treatment that is not compatible with the study protocol; presence or history of other conditions that are not compatible with the study protocol.

Interventions

BIOLOGICAL

CTX112

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Conditions

SLE (Systemic Lupus)Lupus Erythematosus, SystemicLupus NephritisSystemic SclerosisInflammatory Myopathy, IdiopathicMyositisDiffuse Cutaneous Systemic Sclerosis

Locations

Stanford University Medical Center

Redwood City, California 94063

United States

Northwestern Medicine, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois 63110

United States

University of Iowa

Iowa City, Iowa 52242

United States

Manning Family Children's Hospital of New Orleans

New Orleans, Louisiana 70118

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Washington University School of Medicine

St Louis, Missouri 63130

United States

University of North Carolina TraCS Institute - CTRC

Chapel Hill, North Carolina 27599

United States

University of Augsburg

Augsburg, 86156

Germany

Universitätsklinikum Köln

Cologne, 50937

Germany

Medizinische Hochschule Hannover (MHH)

Hanover, 30625

Germany

UCT University Medical Center Mainz

Mainz, 55131

Germany

Research Site 10

Córdoba, 14004

Spain

Research Site 9

Pamplona, 31008

Spain

Research Site 11

Seville, 41013

Spain