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

NCT06857214 | Recruiting Phase 1

• 1 other identifier: GNC-038-106
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (10)

• 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: 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 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 Ib: SRI-4 response rate

  SRI-4 response rate will be investigated.

  Up to approximately 24 months

Secondary Outcomes (6)

• Anti-drug antibody (ADA)

  Up to approximately 24 months

• Phase Ia: Receptor Occupancy (RO)

  Up to approximately 24 months

• Phase Ib: Change from baseline in SLEDAI-2K

  Up to approximately 24 months

• Phase Ib: Changes in Quality of Life (SF-36)

  Up to approximately 24 months

• Phase Ib: Proportion of subjects achieving Lupus Low Disease Activity Status (LLDAS)

  Up to approximately 24 months

Study Arms (2)

GNC-038

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

The control group will be set up in phase Ib, participants will receive placebo.

Drug: Placebo

Interventions

GNC-038 DRUG

Administration by intravenous infusion. Once a week (IV, QW), twice in total.

GNC-038

Placebo DRUG

The control group will be set up in phase Ib, and an appropriate dose will be selected based on phase Ia data.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form;
• No gender limit;
• Age: ≥18 years old and ≤75 years old;
• Life expectancy greater than 6 months;
• SLE was diagnosed according to the 2019 EULAR/ACR revised criteria;
• Patients with moderate to severe systemic lupus erythematosus, SLEDAI-2K score \&gt at screening; 7 points;
• A stable standard-of-care regimen was maintained for at least 30 days before the first dose;
• ANA ≥ 1:80 or anti-dsdna antibody higher than the upper limit of normal range (ULN) as determined by central laboratory at screening;
• The presence of CD19+ B cells in the peripheral blood of the patient;
• The organ function level before the first administration met the requirements;
• 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;
• Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

You may not qualify if:

• Severe lupus nephritis within 8 weeks before screening;
• She had uncontrolled lupus crisis within 8 weeks before screening and was not suitable for the study as assessed by the investigator;
• Active encephalopathy or psychosis within 6 months before screening;
• Primary diagnosis of different autoimmune or inflammatory diseases;
• B cell-depleting therapy within 6 months before initiation of GNC-038 treatment;
• Received CAR-T therapy within 6 months before GNC-038 treatment;
• Cytokine-targeting biologic agents used within 12 weeks before dose administration;
• Use of anti-tumor necrosis factor drugs within 8 weeks before administration;
• Use of any JAK inhibitor within 2 weeks before dosing;
• Receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug;
• Major organ transplantation history or hematopoietic stem cell/bone marrow transplantation;
• Presence of: 1) active hepatitis B at screening; 2) hepatitis C or HIV infection; 3) syphilis infection;
• A history of any cardiovascular disease described in the protocol within 6 months before screening;
• Poorly controlled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg);
• Prolonged QT interval at rest (QTcf \> 450 msec in men or \> 470 msec in women);

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead
• Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Sa Xiao, PHD

CONTACT

15013238943; xiaosa@baili-pharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 4, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 24, 2025

Record last verified: 2025-06

Locations

CN (1)