Rheumatoid Arthritis (RA)
Conditions
Keywords
cizutamig, rheumatoid arthritis
Brief summary
The purpose of the study is to evaluate the safety and efficacy of BCMAxCD3 T-cell engager (cizutamig) in patients with refractory seropositive RA.
Detailed description
B cells mature into plasmablasts and plasma cells that are prolific antibody producers and the predominant source of pathogenic autoantibodies, a hallmark of RA. Autoantibodies contribute to the pathogenesis of RA in several ways, including formation of immune complexes, activation of complement and downstream cell lysis. Clinical trials of cizutamig (BCMAxCD3 T-cell engager) demonstrated safety and efficacy in RRMM. Cizutamig offers a promising mechanism of action for refractory seropositive RA. This study aims to assess the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary clinical activity of cizutamig administered in patients with refractory seropositive RA. Patients will be invited to participate in the study, to receive cizutamig and monitored after dosing with cizutamig through Week 52.
Interventions
DRUGCizutamig
Cizutamig will be administered per the dose escalation cohort
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 18 to 75 years old at the time of signing the informed consent form 2. Diagnosis of adult-onset RA as defined by the 2010 ACR/EULAR classification criteria 3. Moderately to severely active RA. 4. Positive test results for RF and/or ACPA at Screening. Inadequate treatment response defined as either lack of clinical benefit or intolerability to treatment with tsDMARD and/or bDMARD
Exclusion criteria
1. Inadequate clinical laboratory parameters at Screening 2. Patients with active infection 3. Receipt of live vaccine within 4 weeks prior to Screening 4. Presence of any concomitant autoimmune disease 5. History of progressive multifocal leukoencephalopathy 6. History of primary immunodeficiency or a hereditary deficiency of the complement system 7. Central nervous system disease 8. Presence of 1 or more significant concurrent medical conditions per investigator judgment 9. Have a diagnosis or history of malignant disease within 5 years 10. Serious mental illness, alcohol or drug abuse, dementia, or any other condition that would impair the patient's ability to receive the planned treatment or to understand informed consent at the study site as determined by local practice
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in safety laboratory assessments through end of study: hematology | Baseline to Month 12 | — |
| Changes from baseline in vital signs through end of study: blood pressure | Baseline to Month 12 | — |
| Changes from baseline in vital signs through end of study: pulse oximetry | Baseline to Month 12 | — |
| Changes from baseline in ECG parameters through end of study: PR interval | Baseline to Month12 | — |
| Changes from baseline in ECG parameters through end of study: QRS interval | Baseline to Month 12 | — |
| Changes from baseline in ECG parameters through end of study: QTcF interval | Baseline to Month 12 | — |
| Changes from baseline in safety laboratory assessments through end of study: serum chemistry | Baseline to Month 12 | — |
| Incidence and severity of treatment-emergent adverse events through end of study | Baseline to Month 12 | Incidence and severity of TEAEs through end of study. |
| Changes from baseline in vital signs through end of study: body temperature | Baseline to Month 12 | — |
| Changes from baseline in vital signs through end of study: heart rate | Baseline to Month 12 | — |
| Changes from baseline in vital signs through end of study: respiratory rate | Baseline to Month 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters for Cizutamig: time of maximum concentration | Baseline to Month 12 |
| PK parameters for Cizutamig: area under the concentration-time curve | Baseline to Month 12 |
| PK parameters for Cizutamig: clearance | Baseline to Month 12 |
| PK parameters for Cizutamig: volume of distribution | Baseline to Month 12 |
| PK parameters for Cizutamig: half-life | Baseline to Month 12 |
| Pharmacokinetic (PK) for Cizutamig: Cmax | Baseline to Month 12 |
Countries
China
Contacts
Primary ContactQiubai Li, Professor
Backup ContactDi Wu
Outcome results
None listed