An Open-label Study of GB261 in Refractory Seropositive Systemic Lupus Erythematosus

NCT ID: NCT06945068

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2026-11-30

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of CD20xCD3 T-cell engager (GB261) in patients with refractory seropositive systemic lupus erythematosus.

Detailed Description

B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). CD20 is a transmembrane receptor that is highly expressed on approximately 95% of B lineage cells. The use of anti-CD20 for B cell depletion represents a significant breakthrough in the treatment of B-cell-mediated autoimmune diseases. GB261 is a novel CD20/CD3 bispecific TCE that is designed to have very low affinity for CD3 and high affinity for CD20 to enable efficient T cell-mediated killing while minimizing risk of cytokine release syndrome (CRS). GB261 has shown promising safety and anti-tumor activity in a Phase 1/2 study in patients with relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. GB261 offers a promising mechanism of action for SLE. This study aims to assess the safety, tolerability, PK, pharmacodynamics (PD), immunogenicity, and preliminary clinical activity of GB261 administered in patients with SLE. Patients will be invited to participate in the study, to receive GB261 intravenous infusion and monitored from the first dose of GB261 until Week 52.

Conditions

Systemic Lupus Erythematosus (SLE)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GB261 intravenous intervention

GB261 will be administered by intravenous infusion, including 3 escalating dose levels and subsequent dose expansion. Timepoint of treatment: Day 1, Day 8 and Day 15. Anticipated enrollment: 9-18 participants in Dose Escalation group; 10 participants in Dose Expansion group.

Group Type: EXPERIMENTAL

GB261

Intervention Type: BIOLOGICAL

GB261 will be dosed according to the assigned group.

Interventions

GB261

GB261 will be dosed according to the assigned group.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. 18 to 75 years old at the time of signing the informed consent form (ICF)

2. Diagnosis of SLE according to the 2019 American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR) classification criteria

3. 3. Positive for 2 out of 3 antibodies at Screening: a. Anti-dsDNA; b. Anti-Smith antibodies; c. Antinuclear antibody (ANA) titer ≥1:80

4. Active SLE disease

5. Inadequate response

6. Current and stable use of some medication up to Day 1

7. Current and stable use of some medication must be discontinued ≥1 week prior to Day 1

SLE patients with active LN are eligible to be included in the study only if all of the following additional criteria apply:

1. Active, biopsy-proven, proliferative LN Class III or IV according to the 2018 International Society of Nephrology/Renal Pathology Society criteria

2. Inadequate response

3. Stable angiotensin-converting enzyme inhibitors/angiotensin receptor blockers for at least 4 weeks prior to Screening

Exclusion Criteria

1. Inadequate clinical laboratory parameters at Screening:

2. Patients will be excluded if they are known to have 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 prior to Screening

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. History of or planned organ transplant and/or autologous or allogeneic hematopoietic stem cell transplantation for the duration of the study.

17. 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).

18. Any serious medical condition or abnormality on clinical laboratory testing

19. Women who are pregnant or breastfeeding.

20. Sexually active male patients who do not agree to refrain from donating semen

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Qiubai Li

Director, Head of Department of Rheumatology and Immunology, Principal Investigator, Professor, Wuhan Union Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qiubai Li, Professor

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Wuhan Union Hospital

Wuhan, Hubei, China

Countries

China

Central Contacts

Qiubai Li, Professor

Role: CONTACT

qiubaili@hust.edu.cn

85726808 ext. 027

Di Wu

Role: CONTACT

373181302@qq.com

+8618790696175 ext. 86

Facility Contacts

Qiubai Li, Professor

Role: primary

qiubaili@hust.edu.cn

85726808 ext. 027

Lijuan Jiang, PhD

Role: backup

85726808 ext. 027

Other Identifiers

UHCT250170

Identifier Type: -

Identifier Source: org_study_id