GNC-038 tetra-specific antibody injection for adults with moderate-to-severe systemic lupus erythematosus

A Randomized Controlled Phase I Clinical Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of GNC-038 Tetra-specific Antibody Injection in Systemic Lupus Erythematosus

This study will test whether GNC-038, a tetra-specific antibody injection, is safe and can reduce disease activity in adults with moderate-to-severe systemic lupus erythematosus.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06857214 on ClinicalTrials.gov

What this trial studies

This phase I program starts with a phase Ia single-arm dose-escalation portion and proceeds to a randomized, placebo-controlled phase Ib. The trial will collect safety, pharmacokinetic/pharmacodynamic (PK/PD), and preliminary efficacy data in patients with measurable disease activity and autoantibody positivity. Phase Ia will identify tolerated dose ranges and characterize PK/PD, and phase Ib will compare active dosing against placebo while participants remain on stable background standard-of-care therapy. The study is being conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine.

Who should consider this trial

Good fit: Adults 18–75 years old with moderate-to-severe SLE (SLEDAI-2K >7), positive ANA or elevated anti-dsDNA, detectable peripheral CD19+ B cells, a stable standard-of-care regimen for ≥30 days, and life expectancy >6 months are the intended participants.

Not a fit: Patients with mild SLE, absent peripheral CD19+ B cells, significant organ dysfunction, pregnancy, or those outside the 18–75 age range are unlikely to benefit from this early-phase study.

Why it matters

Potential benefit: If successful, GNC-038 could provide a new targeted therapy that lowers lupus activity and reduces flares for patients who do not respond fully to current treatments.

How similar studies have performed: B-cell–targeted therapies such as rituximab and belimumab have benefited some SLE patients, but tetra-specific antibodies like GNC-038 are a novel approach that has not yet been proven in humans.

Eligibility criteria

Inclusion Criteria:

1. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form;
2. No gender limit;
3. Age: ≥18 years old and ≤75 years old;
4. Life expectancy greater than 6 months;
5. SLE was diagnosed according to the 2019 EULAR/ACR revised criteria;
6. Patients with moderate to severe systemic lupus erythematosus, SLEDAI-2K score \&gt at screening; 7 points;
7. A stable standard-of-care regimen was maintained for at least 30 days before the first dose;
8. ANA ≥ 1:80 or anti-dsdna antibody higher than the upper limit of normal range (ULN) as determined by central laboratory at screening;
9. The presence of CD19+ B cells in the peripheral blood of the patient;
10. The organ function level before the first administration met the requirements;
11. Female subjects of childbearing potential or male subjects with a fertile partner must use highly effective contraception from 7 days before the first dose until 24 weeks after the termination of treatment and should commit not to donate eggs (eggs, oocytes)/sperm for assisted reproduction for 1 year after the last study treatment. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose;
12. Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

1. Severe lupus nephritis within 8 weeks before screening;
2. She had uncontrolled lupus crisis within 8 weeks before screening and was not suitable for the study as assessed by the investigator;
3. Active encephalopathy or psychosis within 6 months before screening;
4. Primary diagnosis of different autoimmune or inflammatory diseases;
5. B cell-depleting therapy within 6 months before initiation of GNC-038 treatment;
6. Received CAR-T therapy within 6 months before GNC-038 treatment;
7. Cytokine-targeting biologic agents used within 12 weeks before dose administration;
8. Use of anti-tumor necrosis factor drugs within 8 weeks before administration;
9. Use of any JAK inhibitor within 2 weeks before dosing;
10. Receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug;
11. Major organ transplantation history or hematopoietic stem cell/bone marrow transplantation;
12. Presence of: 1) active hepatitis B at screening; 2) hepatitis C or HIV infection; 3) syphilis infection;
13. A history of any cardiovascular disease described in the protocol within 6 months before screening;
14. Poorly controlled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg);
15. Prolonged QT interval at rest (QTcf \> 450 msec in men or \> 470 msec in women);
16. A history of ≥ grade 2 bleeding within 30 days before screening or the need for long-term continuous anticoagulant therapy;
17. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-038;
18. Women who are pregnant or breastfeeding;
19. Have a history or evidence of suicidal thoughts within 6 months before signing ICF, which is considered by the researcher to be a significant risk of suicide;
20. Diagnosed with malignant tumor within 5 years before signing ICF;
21. Other situations of poor compliance, unwillingness or inability to comply with the study protocol as judged by the investigator;
22. History of splenectomy;
23. Investigators considered a history of alcohol or drug abuse in the 12 months before screening;
24. Any active infection requiring systemic antibiotic treatment within 2 weeks before or during screening;
25. A history of severe and/or disseminated viral infection;
26. Active M. tuberculosis infection may be present.

Where this trial is running

Shanghai, Shanghai Municipality

• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Sa Xiao, PHD

Conditions: Systemic Lupus Erythematosus