Clinical trial NCT06857227: A Study of GNC-038 Tetra-specific Antibody Injection in Patients With Rheumatoid Arthritis
Official title: A Randomized Controlled Phase l Clinical Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of GNC-038 Tetra-specific Antibody Injection in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2025-03-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized controlled phase I clinical study with safety, efficacy, and pharmacokinetic/pharmacodynamic characteristics in patients with rheumatoid arthritis.

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.

Eligibility criteria: 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. Patients diagnosed with rheumatoid arthritis according to 1987 or 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria;
6. Patients were moderately to severely active RA at the time of screening;
7. A stable standard-of-care regimen was maintained for at least 30 days before the first dose;
8. Previous treatment with antirheumatic drugs other than MTX: Leflunomide should be discontinued at least 8 weeks before the start of study treatment or cholestyramine should be used for 14 days;
9. Erythrocyte sedimentation rate (ESR) \> 28mm/hr or C-reactive protein (CRP) \> 10mg/L;
10. Positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies;
11. There were CD19+ B cells in the peripheral blood of the patient;
12. Diagnosis of rheumatoid arthritis (RA) more than 6 months;
13. The organ function level before the first administration met the requirements;
14. Fertile female subjects or male subjects with fertile partners 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;
15. Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

1. Confirmed diagnosis of another autoimmune rheumatic disease;
2. B cell-targeted therapy agents administered within 6 months before GNC-038 treatment;
3. Received CAR-T therapy within 6 months before GNC-038 treatment;
4. Use of anti-TNF drugs within 8 weeks before administration;
5. Use of any JAK inhibitor within 2 weeks before dosing;
6. Antimalarial drugs, sulfasalazine, penicillamine, etc. were used within 4 weeks before the drug administration;
7. Use of phytochemicals within 4 weeks before administration;
8. The use of other biological agents or other non-B cell depleting clinical investigational drugs before drug administration did not exceed 5 half-lives;
9. Received an intra-articular injection within 4 weeks before study entry;
10. Receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug;
11. ACR functional class IV or bedridden/wheelchair-bound;
12. History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation;
13. Presence of: 1) active hepatitis B at screening; 2) hepatitis C or HIV infection; 3) syphilis infection;
14. A history of any cardiovascular disease described in the protocol within 6 months before screening;
15. Poorly controlled hypertension (systolic blood pressure \&gt; 160 mmHg or diastolic blood pressure \&gt; 100 mmHg);
16. Prolonged QT interval at rest (QTcf \> 450 msec in men or \> 470 msec in women);
17. A history of ≥ grade 2 bleeding within 30 days before screening or the need for long-term continuous anticoagulant therapy;
18. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-038;
19. Women who are pregnant or breastfeeding;
20. Having 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;
21. Diagnosed with malignant tumor within 5 years before signing ICF;
22. Other situations of poor compliance, unwillingness or inability to comply with the study protocol as judged by the investigator;
23. History of splenectomy;
24. Investigators considered a history of alcohol or drug abuse in the 12 months before screening;
25. Any active infection requiring systemic antibiotic treatment within 2 weeks before or during screening;
26. A history of severe and/or disseminated viral infection;
27. Active M. tuberculosis infection may be present.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to approximately 28 days
measure: Phase Ia: Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
timeFrame: Up to approximately 28 days
measure: Phase Ia: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Phase Ia: Cmax
timeFrame: Up to approximately 24 months
measure: Phase Ia: Tmax
timeFrame: Up to approximately 24 months
measure: Phase Ia: T1/2
timeFrame: Up to approximately 24 months
measure: Phase Ia: AUC0-t
timeFrame: Up to approximately 24 months
measure: Phase Ia: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Proportion of patients meeting ACR20 remission criteria
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
measure: Phase Ia: Receptor Occupancy (RO)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Change from baseline in quality of life (SF-36)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Change from baseline in DAS28 CRP
timeFrame: Up to approximately 24 months
measure: Phase Ib: Proportion of patients meeting ACR50 response criteria
timeFrame: Up to approximately 24 months
measure: Phase Ib: Proportion of patients meeting ACR70 response criteria
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: