Systemic Lupus Erythematosus (SLE)
Conditions
Keywords
Systemic Lupus Erythematosus, GB261
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.
Interventions
BIOLOGICALGB261
GB261 will be dosed according to the assigned group.
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 (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 Additional Inclusion Criteria for SLE with Active LN 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | Baseline to Month 12 | Incidence and severity of TEAEs through end of study. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded by ASTCT criteria, other AEs are assessed by CTCAE V5.0 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of GB261 | Baseline to Month 12 (Day1-4, 8-11, 15-18, 22, 29, 36 Week 8, 52) | PK profiles and parameters, including Peak Plasma Concentration (Cmax), derived for GB261 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient-reported outcomes | Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52) | Change from baseline through Week 52 in Health Assessment Questionnaire - Disability Index (HAQ-DI). Range \[0, 3\], higher score represents more severe disability. |
| Pharmacodynamics of GB261 | Baseline to Month 12(Screening, Day1, Day 8, 15, 22, 29, 36, Week 8, 16, 24, 36, 52) | Changes from baseline in CD19+ B cells counts. |
| Clinical activity of GB261 | Baseline to Month 12 (Screening, Day1, Day 8, 15, 29, Week 8, 12, 16, 24, 36, 52) | Change from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Range\[0, 105\], higher score represents worse disease activity |
| Effect on affected tissues | From the baseline to Month 12 (Screening and Day 29). | Changes from baseline in cellular composition. Lymph node biopsy or Bone marrow biopsy. |
| Immunogenicity of GB261 | Baseline to Month 12 (Day1, Day 8, 15, 22, 29, 36, Week 8, 12, 16, 24, 52) | Proportion of patients with ADAs before and after treatment |
Countries
China
Contacts
Primary ContactQiubai Li, Professor
Backup ContactDi Wu
Outcome results
None listed