Diffuse Cutaneous Systemic Sclerosis, Inflammatory Myopathy, Idiopathic, Lupus Erythematosus, Systemic, Lupus Nephritis, Myositis, SLE (Systemic Lupus), Systemic Sclerosis
Conditions
Keywords
CAR T, Lupus, SLE, Lupus Nephritis, Allogeneic, CD19, Cell Therapy, Scleroderma, Myositis, Systemic sclerosis, Idiopathic Inflammatory Myopathy, Inflammatory Myopathy, Diffused Cutaneous Systemic Sclerosis, Gene Therapy, Autoimmune, SSc, IIM
Brief 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).
Interventions
BIOLOGICALCTX112
CTX112 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components)
Sponsors
CRISPR Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety of CTX112 in adult subjects with refractory autoimmune diseases, including SLE, SSc or IIM | From CTX112 infusion up to 28 days post-infusion | Incidence of dose-limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the pharmacodynamic response of CTX112 in adult subjects with refractory autoimmune diseases, including SLE, SSc or IIM | From CTX112 infusion up to 60 months post-infusion | Change from baseline in disease specific autoantibody markers |
| To assess the pharmacokinetics (PK) of CTX112 in adult subjects with refractory autoimmune diseases, including SLE, SSc or IIM | From CTX112 infusion up to 60 months post-infusion | Levels of CTX112 in blood over time |
| To assess the preliminary efficacy of CTX112 in adult subjects with refractory autoimmune diseases, including active SLE, SSc or IIM. | From CTX112 infusion up to 60 months post-infusion | For SLE subjects: disease response rates based on SLEDAI-2K instrument; DORIS and LLDAS criteria For SSc subjects: disease response rates based on ACR-CRISS (including mRSS, forced vital capacity, HAQ-DI, Physician Global Assessment, Patient Global Assessment) For IIM subjects: disease response rates based on ACR/EULAR total Improvement score (including MMT8, EMDA, forced vital capacity, Physician Global Assessment, Patient Global Assessment, muscle enzyme level) |
Countries
Germany, Spain, United States
Contacts
CONTACTClinical Trials
Outcome results
None listed