Autoimmune Diseases, Myositis, Systemic Lupus Erythematosus, Systemic Scleroderma
Conditions
Brief summary
Patients with refractory autoimmune diseases often have limited treatment options and ongoing disease activity despite standard therapies. CRT-402 is an in vivo Cluster of differentiation 19 (CD19)-targeted CAR-T cell therapy designed to deplete CD19-positive B cells and promote immune system reset. This study evaluates the safety, tolerability, preliminary efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of CRT-402 in participants with active refractory systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM).
Detailed description
This is a multicenter, open-label, Phase 1/2, first-in-human, dose escalation and expansion study designed to assess the safety and tolerability, as well as define the recommended Phase 2 dose (RP2D) of CRT-402 in participants with refractory autoimmune disease.
Interventions
DRUGCRT-402
CRT-402 administered by intravenous infusion.
Sponsors
Myeloid Therapeutics
CREATE Medicines
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * Diagnosis of active, refractory systemic lupus erythematosus, systemic sclerosis, or idiopathic inflammatory myopathy meeting established classification criteria, with inadequate response or intolerance to standard therapy. * Adequate renal, hepatic, cardiac, and pulmonary function per protocol-defined criteria. * Participants of reproductive potential must agree to use protocol-specified contraception during the study and for a defined period after dosing. * Females of childbearing potential must have a negative pregnancy test before treatment. * Must be willing and able to attend study visits and follow all study requirements.
Exclusion criteria
* Clinical suitability for a less burdensome and/or approved therapeutic approach, as judged by the Investigator, * Any medical condition or laboratory abnormality that, in the Investigator's judgment, would place the participant at unacceptable risk or confound interpretation of study data, * Prior Cluster of differentiation 19 (CD19)-directed, cell, or gene therapy, * History of bone marrow/ hematopoietic stem cell or solid organ transplantation, * Active or inadequately treated infection, including Human immunodeficiency (HIV), hepatitis B or C, or tuberculosis, * Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), and dose-limiting toxicities (DLTs). | Up to 52 weeks | Adverse events (AEs) are any new or worsening medical problems that occur after starting the study treatment. |
| Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). | Up to 52 weeks | cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome ICANS will be graded using standard consensus criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess emergence of anti-drug antibodies (ADAs) | Up to 52 weeks | Serum for anti-drug antibody analysis will be collected at designated visits indicated in the Schedule of Assessments (SOA). Samples will be collected using standard site practices. |
| Pharmacokinetic parameter: Maximum observed plasma concentration (Cmax) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Area under the curve (AUC) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Time to Maximum Concentration (tmax) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Plasma clearance (CL) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Volume of distribution (Vd) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Mean Residence Time (MRT) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Apparent terminal half-life (t1/2) | Day 1 through Day 22 | — |
| Pharmacokinetic parameter: Terminal elimination rate constant (λz). | Day 1 through Day 22 | — |
| Overall Response Rate (ORR), measured by disease-specific composite response criteria. | Week 24 | — |
Countries
Australia
Contacts
CONTACTClinical Department
STUDY_DIRECTORAdam Raff, MD, PhD
SVP Clinical Development, CREATE Medicines
Outcome results
None listed