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

Overview

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.

Interventions

• Drug GNC-038
  Administration by intravenous infusion. Once a week (IV, QW), twice in total.
• Drug Placebo
  The control group will be set up in phase Ib, and an appropriate dose will be selected based on phase Ia data.

Primary outcome measures

• Phase Ia: Dose limiting toxicity (DLT) [Time frame: Up to approximately 28 days]
• Phase Ia: Maximum tolerated dose (MTD) or Maximum administered dose (MAD) [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: Proportion of patients meeting ACR20 remission criteria [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 quality of life (SF-36) [Time frame: Up to approximately 24 months]
• Phase Ib: Change from baseline in DAS28 CRP [Time frame: Up to approximately 24 months]
• Phase Ib: Proportion of patients meeting ACR50 response criteria [Time frame: Up to approximately 24 months]
• Phase Ib: Proportion of patients meeting ACR70 response criteria [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;
• Patients diagnosed with rheumatoid arthritis according to 1987 or 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria;
• Patients were moderately to severely active RA at the time of screening;
• A stable standard-of-care regimen was maintained for at least 30 days before the first dose;
• 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;
• Erythrocyte sedimentation rate (ESR) > 28mm/hr or C-reactive protein (CRP) > 10mg/L;
• Positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies;
• There were CD19+ B cells in the peripheral blood of the patient;
• Diagnosis of rheumatoid arthritis (RA) more than 6 months;
• The organ function level before the first administration met the requirements;
• 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;
• Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Confirmed diagnosis of another autoimmune rheumatic disease;
• B cell-targeted therapy agents administered within 6 months before GNC-038 treatment;
• Received CAR-T therapy within 6 months before GNC-038 treatment;
• Use of anti-TNF drugs within 8 weeks before administration;
• Use of any JAK inhibitor within 2 weeks before dosing;
• Antimalarial drugs, sulfasalazine, penicillamine, etc. were used within 4 weeks before the drug administration;
• Use of phytochemicals within 4 weeks before administration;
• The use of other biological agents or other non-B cell depleting clinical investigational drugs before drug administration did not exceed 5 half-lives;
• Received an intra-articular injection within 4 weeks before study entry;
• Receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug;
• ACR functional class IV or bedridden/wheelchair-bound;
• History of major organ transplantation 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;
• 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;
• 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: NCT06857227 · GNC-038-107

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗