Evaluating CTX112 for treating refractory autoimmune diseases in adults

A Phase 1 Dose Evaluation Study of the Safety and Preliminary Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Adult Subjects With Refractory Autoimmune Disease

This study is testing a new CAR T cell treatment called CTX112 to see if it can help adults with tough autoimmune diseases like lupus and scleroderma feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: CRISPR Therapeutics (Industry-sponsored)
• Drugs / interventions: CAR T, chimeric antigen receptor, immunotherapy
• Locations: 8 sites (Redwood City, California and 7 other locations)
• Trial ID: NCT06925542 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label, multicenter Phase 1 study assessing the safety and preliminary efficacy of CTX112, a CAR T cell immunotherapy, in adults with refractory autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis, and idiopathic inflammatory myopathy. The study aims to enroll up to 80 subjects who will receive genetically modified T cells derived from healthy donors, utilizing CRISPR-Cas9 technology for treatment. Participants will be monitored for safety and effectiveness throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with a diagnosis of systemic lupus erythematosus, systemic sclerosis, or idiopathic inflammatory myopathy.

Not a fit: Patients with autoimmune diseases that are not refractory or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from refractory autoimmune diseases.

How similar studies have performed: Other studies utilizing CAR T cell therapies have shown promise in treating various conditions, suggesting potential success for this novel approach in autoimmune diseases.

Eligibility 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.

Where this trial is running

Redwood City, California and 7 other locations

• Research Site 4 — Redwood City, California, United States (Recruiting)
• Research Site 2 — Chicago, Illinois, United States (Recruiting)
• Research Site 8 — Iowa City, Iowa, United States (Recruiting)
• Research Site 6 — Boston, Massachusetts, United States (Recruiting)
• Research Site 1 — St Louis, Missouri, United States (Recruiting)
• Research Site 5 — Chapel Hill, North Carolina, United States (Recruiting)
• Research Site 7 — Augsburg, Germany (Not_yet_recruiting)
• Research Site 3 — Hanover, Germany (Recruiting)

Study contacts

• Study coordinator: Clinical Trials

Conditions SLE; Lupus Erythematosus, Systemic; Lupus Nephritis; Systemic Sclerosis; Inflammatory Myopathy, Idiopathic; Myositis; Diffuse Cutaneous Systemic Sclerosis; CAR T