A Study of GNC-038 Tetra-specific Antibody Injection in Patients With Systemic Lupus Erythematosus

Phase 1

Not yet recruiting

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: Placebo; Drug: GNC-038

• Registration Number: NCT06857214
• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

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.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-26
• Study First Submitted QC: 2025-02-26
• Last Update Submitted: 2025-02-26
• Study Start: 2025-03
• Study First Posted: 2025-03-04
• Last Update Posted: 2025-03-04
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 54

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The control group will be set up in phase Ib, participants will receive placebo.
GNC-038	GNC-038	Participants receive GNC-038 in the first cycle. Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.

Primary Outcome Measures

Name	Time	Method
Phase Ia: Dose limiting toxicity (DLT)	Up to approximately 28 days	DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)	Up to approximately 28 days	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Phase Ia: Treatment-Emergent Adverse Event (TEAE)	Up to approximately 24 months	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-038. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-038.
Phase Ia: Cmax	Up to approximately 24 months	Maximum serum concentration (Cmax) of GNC-038 will be investigated.
Phase Ia: Tmax	Up to approximately 24 months	Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.
Phase Ia: T1/2	Up to approximately 24 months	Half-life (T1/2) of GNC-038 will be investigated.
Phase Ia: AUC0-t	Up to approximately 24 months	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
Phase Ia: CL (Clearance)	Up to approximately 24 months	CL in the serum of GNC-038 per unit of time will be investigated.
Phase Ib: Recommended Phase II Dose (RP2D)	Up to approximately 24 months	The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-038.
Phase Ib: SRI-4 response rate	Up to approximately 24 months	SRI-4 response rate will be investigated.

Secondary Outcome Measures

Name	Time	Method
Anti-drug antibody (ADA)	Up to approximately 24 months	Frequency of anti-GNC-038 antibody (ADA) will be investigated.
Phase Ia: Receptor Occupancy (RO)	Up to approximately 24 months	Receptor Occupancy (RO) will be investigated.
Phase Ib: Change from baseline in SLEDAI-2K	Up to approximately 24 months	Change from baseline in SLEDAI-2K will be investigated.
Phase Ib: Changes in Quality of Life (SF-36)	Up to approximately 24 months	Changes in Quality of Life (SF-36) will be investigated.
Phase Ib: Proportion of subjects achieving Lupus Low Disease Activity Status (LLDAS)	Up to approximately 24 months	Proportion of subjects achieving Lupus Low Disease Activity Status (LLDAS) will be investigated.
Phase Ib: Proportion of subjects achieving disease remission (DORIS)	Up to approximately 24 months	Proportion of subjects achieving disease remission (DORIS) will be investigated.

Trial Locations

Locations (1)

Renji Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China