Systemic Lupus Erythematosus
Conditions
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 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
DRUGGNC-038
Administration by intravenous infusion. Once a week (IV, QW), twice in total.
DRUGBelimumab
The first 3 doses are administered once every 2 weeks; starting from the 4th dose, once every 4 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed