A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease
Purpose
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).
Conditions
- SLE (Systemic Lupus)
- Lupus Erythematosus, Systemic
- Lupus Nephritis
- Systemic Sclerosis
- Inflammatory Myopathy, Idiopathic
- Myositis
- Diffuse Cutaneous Systemic Sclerosis
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental CTX112 |
Administered by IV infusion following lymphodepleting chemotherapy |
|
Recruiting Locations
Research Site 4
Redwood City 5386834, California 5332921 94063
Redwood City 5386834, California 5332921 94063
Research Site 2
Chicago 4887398, Illinois 4896861 63110
Chicago 4887398, Illinois 4896861 63110
Research Site 8
Iowa City 4862034, Iowa 4862182 52242
Iowa City 4862034, Iowa 4862182 52242
Research Site 6
Boston 4930956, Massachusetts 6254926 02118
Boston 4930956, Massachusetts 6254926 02118
Research Site 1
St Louis 4407066, Missouri 4398678 63130
St Louis 4407066, Missouri 4398678 63130
Research Site 5
Chapel Hill 4460162, North Carolina 4482348 27599
Chapel Hill 4460162, North Carolina 4482348 27599
More Details
- Status
- Recruiting
- Sponsor
- CRISPR Therapeutics
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).