Clinical trial NCT06857214: A Study of GNC-038 Tetra-specific Antibody Injection in Patients With Systemic Lupus Erythematosus
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2025-03-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, controlled, phase I clinical study with safety, efficacy, and pharmacokinetic/pharmacodynamic characteristics in patients with systemic lupus erythematosus.

Detailed description: This study is divided into a phase Ia study and a phase Ib study. The phase Ib study has a randomized controlled design with a placebo control group. The phase Ia study has a single-arm design, and the phase Ib study will be carried out on the basis of the Phase Ia study.

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.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to approximately 28 days
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to approximately 28 days
measure: Phase Ia: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Phase Ia: Cmax
timeFrame: Up to approximately 24 months
measure: Phase Ia: Tmax
timeFrame: Up to approximately 24 months
measure: Phase Ia: T1/2
timeFrame: Up to approximately 24 months
measure: Phase Ia: AUC0-t
timeFrame: Up to approximately 24 months
measure: Phase Ia: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
measure: Phase Ib: SRI-4 response rate
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
measure: Phase Ia: Receptor Occupancy (RO)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Change from baseline in SLEDAI-2K
timeFrame: Up to approximately 24 months
measure: Phase Ib: Changes in Quality of Life (SF-36)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Proportion of subjects achieving Lupus Low Disease Activity Status (LLDAS)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Proportion of subjects achieving disease remission (DORIS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: