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

Plain English Summary

A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease is a Phase 1 clinical trial sponsored by CRISPR Therapeutics studying SLE (Systemic Lupus), Lupus Erythematosus, Systemic, Lupus Nephritis, Systemic Sclerosis, Inflammatory Myopathy, Idiopathic, Myositis, Diffuse Cutaneous Systemic Sclerosis. This trial tests a new gene-edited cell therapy called CTX112. It is for adults with severe, hard-to-treat autoimmune diseases like lupus, scleroderma, or inflammatory myopathy. Participants will receive CTX112 and be monitored for safety and early signs of effectiveness. There are no approved alternative treatments for patients who haven't responded to standard therapies. The trial aims to enroll 80 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 to 69 can join. You must have a confirmed diagnosis of severe lupus, systemic sclerosis, or inflammatory myopathy that hasn't improved with other treatments. You need to have generally good organ function (heart, lungs, kidneys, liver) and blood counts. You cannot have had prior gene therapy, cell therapy, or organ transplants. This trial is studying SLE (Systemic Lupus), Lupus Erythematosus, Systemic, Lupus Nephritis, Systemic Sclerosis, Inflammatory Myopathy, Idiopathic, Myositis, Diffuse Cutaneous Systemic Sclerosis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how safe CTX112 is by tracking any side effects in the first month after receiving the treatment. The specific primary outcome measures are: 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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial explores a novel gene-editing approach to potentially reset the immune system in patients with severe autoimmune diseases that have not responded to existing treatments. This research targets SLE (Systemic Lupus), Lupus Erythematosus, Systemic, Lupus Nephritis, Systemic Sclerosis, Inflammatory Myopathy, Idiopathic, Myositis, Diffuse Cutaneous Systemic Sclerosis, where improved treatment options are needed.

Investor Insight

This Phase 1 trial represents an early-stage investment in a potentially groundbreaking CRISPR-based therapy for autoimmune diseases, a large and growing market, with a high bar for success due to the Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of CTX112 and how it compares to other treatment options. Participation involves receiving the CTX112 infusion and attending regular follow-up appointments for monitoring over several years. You will need to use effective contraception during the trial. This trial is currently recruiting participants. The trial is being conducted at 8 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 80 participants

Interventions

• BIOLOGICAL: CTX112 — CTX112 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components)

Primary Outcomes

• 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)

Secondary Outcomes

• 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)
• 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)
• 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)

Full 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.

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Systemic Lupus Erythematosus (SLE)
• Lupus Nephritis
• Systemic Sclerosis
• Diffuse Cutaneous Systemic Sclerosis
• Idiopathic Inflammatory Myopathy
• Dermatomyositis
• Polymyositis
• Antisynthetase Syndrome
• Immune-Mediated Necrotizing Myopathy
• Autoimmune Diseases

More SLE (Systemic Lupus) Trials

View all SLE (Systemic Lupus) clinical trials