An Open-label Study of Cizutamig in Refractory Seropositive Rheumatoid Arthritis

An Open-label Study Evaluating the Safety and Preliminary Clinical Activity of Cizutamig in Patients With Refractory Seropositive Rheumatoid Arthritis

The purpose of the study is to evaluate the safety and efficacy of BCMAxCD3 T-cell engager (cizutamig) in patients with refractory seropositive RA.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Cizutamig; Biological: Cizutamig

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn
• Study Contact Backup: Name: Di Wu; Phone Number: 86 18790696175; Email: 373181302@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Wuhan Union Hospital
      • Contact: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn
      • Contact: Cheng Wang, PhD; Phone Number: 027 85726808

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cizutamig	Drug: Cizutamig; Cizutamig will be administered per the dose escalation cohort; Biological: Cizutamig; Cizutamig will be administered per the dose escalation cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
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 safety laboratory assessments through end of study: serum chemistry		Baseline to Month 12
Changes from baseline in safety laboratory assessments through end of study: hematology		Baseline to Month 12
Incidence and severity of treatment-emergent adverse events through end of study	Incidence and severity of TEAEs through end of study.	Baseline to Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic (PK) for Cizutamig: Cmax	Baseline to Month 12
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics of cizutamig	Changes from baseline in CD19+ B cells counts	Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 8, 12, 16, 24, 36, 52)
Pharmacodynamics of cizutamig	Changes from baseline in inflammatory cytokines	Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 52)
Pharmacodynamics of cizutamig	Changes from baseline in soluble BCMA	Baseline to Month 12 (Screening, Day1, Day 8, 15, 22, 29, 36, Week 52)
Immunogenicity of cizutamig	Proportion of patients with ADAs before and after treatment	Baseline to Month 12 (Day1, Day 8, 15, 22, 29, 36, Week 8, 12, 16, 24, 52)
Patient-reported outcomes	Change from baseline through Week 52 in HAQ-DI. Range [0, 3]，higher score represents more severe disability.	Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52)
Effect on affected tissues	Changes from baseline in cellular composition. Lymph node biopsy or Bone marrow biopsy.	From the baseline to Month 12 (Screening and Day 29)
Clinical activity of cizutamig	Change from baseline in DAS28-hsCRP, higher score represents worse disease activity	Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52)

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Principal Investigator: Qiubai Li, Professor, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; cizutamig
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: UHCT250171

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No