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

A Phase 1/2 Dose Evaluation Trial of the Safety and Preliminary Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Adult Participants With Refractory Neurologic Autoimmune Disease.

This is a single-arm, open-label, multicenter, ascending dose Phase 1/2 trial evaluating the safety and preliminary efficacy of CTX112 in adult participants with neurological autoimmune diseases (AIDs), including Progressive Multiple Sclerosis, relapsing Neuromyelitis Optica Spectrum Disorder, relapsing Myelin Oligodendrocyte Glycoprotein Antiody-Associated Disease, refractory AutoImmune Encephalitis, and refractory Stiff Person Syndrome

This trial will evaluate the safety and preliminary efficacy of CTX112 in adult participants with Progressive Multiple Sclerosis (PMS), relapsing Neuromyelitis Optica Spectrum Disorder (NMOSD), relapsing Myelin Oligodendrocyte Glycoprotein Antiody-Associated Disease (MOGAD), refractory AutoImmune Encephalitis (AIE), and refractory Stiff Person Syndrome (SPS). PMS, NMOSD, MOGAD, AIE, and SPS are neurological AIDs where B cells play a significant role. Compartmentalized central nervous system (CNS) inflammation can also occur, leaving a proportion of patients unresponsive to biologics, including clusters of differentiation 19 and 20 (CD19 and CD20)-monoclonal antibodies (mAbs). Both anti-CD19 and anti-CD20 mAbs penetrate the blood-brain barrier (BBB) poorly, limiting the degree of B-cell depletion attainable within the CNS compartment. No curative treatment exists for these conditions, and despite the best available therapies a substantial proportion of patients continue to experience relapses and/or accruing disability and suffer from low quality of life combined with high morbidity and mortality. Current options focus largely on treating or preventing relapses, typically with peripherally acting agents that require repeated parenteral administration. This underscores an urgent need for novel therapies able to cross the BBB and target the CNS B-cell compartment, thereby potentially eliciting a deep immune reset and durable remission in patients who have failed multiple lines of standard therapy. Preliminary evidence suggests that chimeric antigen receptor (CAR) T cells may offer long-lasting benefits, with extended treatment-free remissions and a manageable safety and tolerability profile.CTX112 is a CD19 directed CAR-T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of refractory autoimmune diseases. The cells are collected from healthy adult volunteer donors and 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). As with autologous CD19-targeting CAR T cell therapy, CTX112 has the potential to generate clinical responses in patients with PMS, relapsing NMOSD, relapsing MOGAD, refractory AIE and SPS following a one-time treatment, but with the benefit of immediate availability and without the need for the patient to undergo apheresis for collection of T cells.

This trial may enroll up to 220 participants. The total duration of trial intervention for each participant is up to 5 years.

Inclusion Criteria:

1. Age ≥18 years and <70 years at screening.
2. Body weight >40 kg.
3. Participants must voluntarily sign a written informed consent and be willing and able to comply with all trial requirements. Legal authorized representative, additional assent and witness may be used as appropriate.
4. Adequate hematologic, renal, liver, cardiac and pulmonary function.
5. Participants must agree to use acceptable methods of contraception.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other trial procedures.
7. Confirmed diagnosis of PMS, relapsing NMOSD, relapsing MOGAD, refractory AIE, and refractory SPS

Exclusion Criteria:

1. Prior treatment with any gene therapy or genetically modified cell therapy.
2. Prior solid organ (e.g., heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
3. Presence of another clinically significant central nervous (CNS) pathology or another condition that in the opinion of the investigator may increase CART cell-related toxicities or confound disease assessments for the main indication.
4. Presence of other active autoimmune disease or other conditions that are likely to pose increased safety risks and/or confound disease assessments, or pose significant risk to those receiving CART cell therapy.
5. Presence or history of certain bacterial, viral or fungal infection.
6. Malignancy in the last 5 years (with the exception of cancers deemed to be low likelihood for recurrence).
7. History or current diagnosis that requires uninterrupted, ongoing anticoagulation.
8. Pregnant or lactating.
9. 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.
10. History of suicide attempts within 3 years prior to screening.
11. Any contraindications to lumbar puncture or MRI scans