Clinical trial NCT06946199: An Open-label Study of Cizutamig in Refractory Seropositive Rheumatoid Arthritis
Official title: An Open-label Study Evaluating the Safety and Preliminary Clinical Activity of Cizutamig in Patients With Refractory Seropositive Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Rheumatoid Arthritis (RA)
Keywords: cizutamig
rheumatoid arthritis
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2025-04-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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. Cizutamig is designed to have high affinity for BCMA and relatively low affinity for CD3 to achieve elimination of autoantibody-producing cells and reduce cytokine production and the risk of CRS. Clinical trials of Cizutamig 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 (PD), 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 intravenous infusion and monitored from the first dose of cizutamig until Week 52.

Eligibility criteria: Inclusion Criteria:

1. 18 to 75 years old at the time of signing the informed consent form (ICF)
2. Diagnosis of adult-onset RA as defined by the 2010 ACR/EULAR classification criteria for at least 3 months prior to Screening.
3. Class I-III RA
4. Moderately to severely active RA.
5. Positive test results for RF and/or ACPA at Screening.
6. Inadequate treatment response defined as either lack of clinical benefit or intolerability to treatment with at least 1 tsDMARD and/or bDMARD after 12 weeks of treatment duration
7. Stable use of any of the background therapy (alone or in combination) up to Day 1

Exclusion Criteria:

1. Inadequate clinical laboratory parameters at Screening
2. Patients with active infection
3. Receipt of or inability to discontinue any excluded therapies
4. Receipt of live vaccine within 4 weeks prior to Screening
5. Presence of any concomitant autoimmune disease
6. Active or known history of catastrophic anti-phospholipid syndrome (APS)
7. APS or thrombotic event not adequately controlled by anticoagulation therapy
8. History of progressive multifocal leukoencephalopathy
9. History of primary immunodeficiency or a hereditary deficiency of the complement system
10. Central nervous system (CNS) disease
11. Presence of 1 or more significant concurrent medical conditions per investigator judgment
12. Have a diagnosis or history of malignant disease within 5 years
13. 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
14. Inability to comply with protocol-mandated requirements
15. History of severe allergic or anaphylactic reactions to mAb therapy (or recombinant antibody-related fusion proteins) or any constituents of study drug.
16. Intolerability to required prophylactic anti-infective medications .
17. History of or planned organ transplant and/or autologous or allogeneic hematopoietic stem cell transplantation for the duration of the study.
18. Major surgery requiring use of general anesthesia within 12 weeks prior to Screening or planned or expected major surgery during the study period (from Screening to patient's last visit).
19. Any serious medical condition or abnormality on clinical laboratory testing
20. Women who are pregnant or breastfeeding.
21. Sexually active male patients who do not agree to refrain from donating semen

Primary outcomes:
measure: Safety and tolerability
timeFrame: Baseline to Month 12
Secondary outcomes:
measure: Pharmacokinetics of cizutamig
timeFrame: Baseline to Month 12 (Day1-4, 8-11, 15, 22, 29, 36 Week 8, 52)
measure: Pharmacokinetics of cizutamig
timeFrame: Baseline to Month 12 (Day1-4, 8-11, 15, 22, 29, 36 Week 8, 52)
measure: Pharmacokinetics of cizutamig
timeFrame: Baseline to Month 12 (Day1-4, 8-11, 15, 22, 29, 36 Week 8, 52)
measure: Pharmacokinetics of cizutamig
timeFrame: Baseline to Month 12 (Day1-4, 8-11, 15, 22, 29, 36 Week 8, 52)
Other outcomes:
measure: Pharmacodynamics of cizutamig
timeFrame: Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 8, 12, 16, 24, 36, 52)
measure: Pharmacodynamics of cizutamig
timeFrame: Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 52)
measure: Pharmacodynamics of cizutamig
timeFrame: Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 52)
measure: Immunogenicity of cizutamig
timeFrame: Baseline to Month 12 (Day1, Day 8, 15, 22, 29, 36, Week 8, 12, 16, 24, 52)
measure: Patient-reported outcomes
timeFrame: Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52)
measure: Effect on affected tissues
timeFrame: From the baseline to Month 12 (Screening and Day 29)
measure: Clinical activity of cizutamig
timeFrame: Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52)
Locations:
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Qiubai Li, Professor
role: PRINCIPAL_INVESTIGATOR
References: