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

Overview

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 Phase Ia and Phase Ib studies. The Phase Ia study adopts a single-arm design, while the Phase Ib study will be conducted on the basis of the Phase Ia study and features an open-label, randomized, active-controlled design, with belimumab as the control agent.

Interventions

• Drug GNC-038
  Administration by intravenous infusion. Once a week (IV, QW), twice in total.
• Drug Belimumab
  The first 3 doses are administered once every 2 weeks; starting from the 4th dose, once every 4 weeks.

Primary outcome measures

• Phase Ia: Dose limiting toxicity (DLT) [Time frame: Up to approximately 28 days]
• Phase Ia: Maximum tolerated dose (MTD) [Time frame: Up to approximately 28 days]
• Phase Ia: Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Phase Ia: Cmax [Time frame: Up to approximately 24 months]
• Phase Ia: Tmax [Time frame: Up to approximately 24 months]
• Phase Ia: T1/2 [Time frame: Up to approximately 24 months]
• Phase Ia: AUC0-t [Time frame: Up to approximately 24 months]
• Phase Ia: CL (Clearance) [Time frame: Up to approximately 24 months]
• Phase Ib: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]
• Phase Ib: SRI-4 response rate [Time frame: Up to approximately 24 months]

Secondary outcome measures (6)

• Anti-drug antibody (ADA) [Time frame: Up to approximately 24 months]
• Phase Ia: Receptor Occupancy (RO) [Time frame: Up to approximately 24 months]
• Phase Ib: Change from baseline in SLEDAI-2K [Time frame: Up to approximately 24 months]
• Phase Ib: Changes in Quality of Life (SF-36) [Time frame: Up to approximately 24 months]
• Phase Ib: Proportion of subjects achieving Lupus Low Disease Activity Status (LLDAS) [Time frame: Up to approximately 24 months]
• Phase Ib: Proportion of subjects achieving disease remission (DORIS) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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);
• A history of ≥ grade 2 bleeding within 30 days before screening or the need for long-term continuous anticoagulant therapy;
• Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-038;
• Women who are pregnant or breastfeeding;
• 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;
• Diagnosed with malignant tumor within 5 years before signing ICF;
• Other situations of poor compliance, unwillingness or inability to comply with the study protocol as judged by the investigator;
• History of splenectomy;
• Investigators considered a history of alcohol or drug abuse in the 12 months before screening;
• Any active infection requiring systemic antibiotic treatment within 2 weeks before or during screening;
• A history of severe and/or disseminated viral infection;
• Active M. tuberculosis infection may be present.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT06857214 · GNC-038-106

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗