A Study of GNC-038 Tetra-specific Antibody Injection in Patients With 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 is a randomized, controlled, phase I clinical study with safety, efficacy, and pharmacokinetic/pharmacodynamic characteristics in patients with systemic lupus erythematosus.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: GNC-038; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: 15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Shuang Ye
      • Principal Investigator: Shuang YE
      • Principal Investigator: Qiong Fu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 > 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: GNC-038; Administration by intravenous infusion. Once a week (IV, QW), twice in total.
Placebo Comparator: Placebo; The control group will be set up in phase Ib, participants will receive placebo.	Drug: Placebo; The control group will be set up in phase Ib, and an appropriate dose will be selected based on phase Ia data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: Dose limiting toxicity (DLT)	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.	Up to approximately 28 days
Phase Ia: Treatment-Emergent Adverse Event (TEAE)	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.	Up to approximately 24 months
Phase Ia: Cmax	Maximum serum concentration (Cmax) of GNC-038 will be investigated.	Up to approximately 24 months
Phase Ia: Tmax	Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.	Up to approximately 24 months
Phase Ia: T1/2	Half-life (T1/2) of GNC-038 will be investigated.	Up to approximately 24 months
Phase Ia: AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.	Up to approximately 24 months
Phase Ia: CL (Clearance)	CL in the serum of GNC-038 per unit of time will be investigated.	Up to approximately 24 months
Phase Ib: Recommended Phase II Dose (RP2D)	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.	Up to approximately 24 months
Phase Ia: Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.	Up to approximately 28 days
Phase Ib: SRI-4 response rate	SRI-4 response rate will be investigated.	Up to approximately 24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 23, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: GNC-038-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No