Rheumatoid Arthritis
Conditions
Interventions
HLX01 group :During the 24-week study, subjects will be given one course of treatment with HLX01, After the Week 24 study visit, all subjects will continue to be given one course of treatment with HLX
placebo group :During the 24-week study, subjects will be given one course of treatment with placebo. After the Week 24 study visit, all subjects will continue to be given one course of treatment with
Sponsors
Chinese Academy of Medical Sciences Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be enrolled into the study: 1. Subjects who are voluntary to participate in the study and sign a written ICF, and willing and able to follow the study protocol (e.g., able to understand and complete the questionnaire, follow the visit plan and use the drug); 2. Aged 18 to 75 years, male or female; 3. Subjects who are diagnosed with moderately to severely active RA with a course of disease of at least 6 months, DAS28 CRP > 3.2 at Screening, and at least 6 swollen joints (based on 66 joints) and at least 6 tender joints (based on 68 joints) at Screening and Baseline (Day 1). If a joint has both swollen and tender symptoms, then this joint should be included in both the SJC and TJC (except for artificial joints); 4. MTX-IR: Subjects must be currently receiving MTX 10-25 mg/week for at least 12 weeks and have been on a stable dose for at least 4 weeks prior to study entry (Day 1). The dose of MTX is expected to remain stable throughout the study and may be adjusted only for s afety reasons; 5. The acceptable RA treatment must meet the following conditions: (1) Subjects are willing to receive oral folic acid therapy (at least 5 mg/week or at a dose determined based on local medical practice) or equivalent medications (combination medications necessary for MTX therapy) during the entire study, and the dose of folic acid or equivalent medications should be stable for a minimum of 4 weeks prior to the start of study treatment (Day 1); (2) If the subject has been previously treated with traditional disease-modifying anti-rheumatic drugs (DMARDs) other than MTX: leflunomide should be discontinued at least 8 weeks prior to the start of study treatment (Day 1), but if they have received standard cholestyramine elution treatment for 11 days, leflunomide will need to be discontinued at least 4 weeks prior to the start of study treatment (Day 1); other DMARDs will need to be discontinued at least 4 weeks prior to the start of study treatment (Day 1). These drugs are not allowed to be used throughout the study. * Standard cholestyramine elution treatment: cholestyramine 8 g orally, three times daily for 11 consecutive days. (3) If the subject is being treated with Tripterygium wilfordii, the drug should be discontinued at least 2 weeks prior to the start of study treatment (Day 1) and is not allowed to be used throughout the study; (4) If the subject is receiving oral glucocorticoid treatment, the dose should not exceed prednisolone 10 mg/day (or equivalent dose of other glucocorticoids), and the dose should have been stable for at least 4 weeks prior to the start of study treatment (Day 1) and remain stable throughout the 24-week treatment period (except for those receiving rescue treatment); if already discontinued, oral glucocorticoids should have been discontinued for at least 2 weeks prior to the start of study treatment (Day 1); (5) Glucocorticoid treatment via intra-articular or injection administration is not allowed within 6 weeks prior to the start of study treatment (Day 1) and during treatment (until Week 24), except for methylprednisolone 80 mg intravenously administered prior to study drug infusion (as this is part of the study process); (6) Any non-steroidal anti-inflammatory drugs (NSAIDs) must have been on a stable dose for a minimum of 2 weeks prior to the start of study treatment (Day 1) and remain on a stable dose throughout the 24-week treatment period (except for t
Exclusion criteria
Exclusion criteria: 1. Previously used TNF-alpha antagonists, other biologics for RA, or targeted synthesized DMARDs (e.g., JAKs enzyme inhibitor Tofacitinib); 2. ACR functional Class IV or bedridden/wheelchair-bound for a long term; 3. Primary or secondary immunodeficiency in previous or current medical history, including known history of HIV infection and positive HIV-; 4. Moderate to severe congestive heart failure (Class III or IV of New York Heart Association); 5. Interstitial lung disease (except mild); 6. Known allergic to murine proteins or other antibodies; 7. History of malignancy, including solid tumors, hematologic tumors and carcinoma in situ(except subjects with previous resected and cured basal or cutaneous squamous cell carcinoma, cervical dysplasia, or in situ Grade I cervical cancer at least 12 months prior to the Screening Visit); 8. Receipt a live vaccine/attenuated vaccine within 12 weeks prior to the Screening Visit until week 48; 9. Any disease or treatments (including biotherapy) that, at the discretion of the Investigator, may bring unacceptable risk to the subject; 10. Pregnant or nursing female subjects, or subjects will pregnant or breastfeeding during the study period or within 12 months of the last dose; 11. Previously or currently suffering from inflammatory joint diseases other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathies, Lyme disease, etc.), or other systemic autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, Felty's syndrome, scleroderma, inflammatory myopathy, mixed connective tissue disease, or any overlap syndromes); 12. Evidence significant uncontrolled concomitant diseases, such as, but not limited to, nervous system, cardiovascular, renal, hepatic, endocrine or gastrointestinal diseases which would preclude patient participation.at the discretion of the Investigator; 13. Positive anti-Hepatitis C virus (HCV) antibody atScreening; 14. Positive anti-Treponema pallidum (TP) antibody at Screening; 15. Positive hepatitis B surface antigen (HBsAg) at Screening; a subject negative for HBsAg yet positive for hepatitis B core antibody (HBcAb) must be further tested for hepatitis B virus (HBV) deoxyribonucleic acid (DNA); only HBV DNA-negative subjects can be enrolled; 16. Any active infection (except nail bed fungal infection), or any serious infection requiring hospitalization or intravenous anti-infection treatment within 4 weeks before the screening visit; or oral anti-infective drug treatment within 2 weeks before the screening visit; 17. History of deep gap/tissue infections (e.g., fasciitis, abscess, osteomyelitis) within 52 weeks prior to the screening visit; 18. History of serious or opportunistic infections in the recent two years at the discretion of the Investigator; 19. History of chronic infections (e.g., chronic pyelonephritis, bronchiectasis or osteomyelitis); 20. Any congenital or acquired neurological, vascular or systemic disease that may affect any of the efficacy evaluations in this study, especially joint pain and swelling (e.g., Parkinson's disease, cerebral palsy, diabetic neuropathy); 21. History of alcohol or drug abuse within 52 weeks prior to the screening visit or subjects currently with alcohol or drug abuse (at the discretion of the Investigator); 22. Received anti-integrin aV antibody or cell depletion therapy including B-cell depletion therapy (e.g., CD20 +, or CD19
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the efficacy between the HLX01 group and the placebo group through the proportion of subjects meeting the ACR20 improvement criteria (or achieve an ACR20 response) at Week 24; | — |
Secondary
| Measure | Time frame |
|---|---|
| ? To compare the efficacy between the HLX01 group and the placebo group through the proportion of subjects meeting the ACR20/50/70 improvement criteria (or ACR20/50/70 responses) at Week 12, 24, 36 and 48 (excluding ACR20 at Week 24). ;? To compare the efficacy between the HLX01 group and the placebo group through the disease activity (Disease Activity Score 28-C-reactive protein [DAS28-CRP] and Disease Activity Score 28-Erythrocyte sedimentation rate [DAS28- ESR]) at Week 12, 24, 36 and 48. ;To compare the efficacy between the HLX01 group and the placebo group through the DAS28 relief and low disease activity status at Week 12, 24, 36 and 48.;? To compare the efficacy between the HLX01 group and the placebo group through the remission of pain at Week 12, 24, 36 and 48.;? To compare the efficacy between the HLX01 group and the placebo group through the physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]) at Week 12, 24, 36 and 48.;? To compare the efficacy between the HLX01 group and the placebo group through the DAS28 relief and low disease activity status at Week 12, 24, 36 and 48.;To compare the efficacy between the HLX01 group and the placebo group through the DAS28 relief and low disease activity status at Week 12, 24, 36 and 48.;? To compare the efficacy between the HLX01 group and the placebo group through the remission of pain at Week 12, 24, 36 and 48.;? To compare the efficacy between the HLX01 group and the placebo group through the physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]) at Week 12, 24, 36 and 48.; | — |
Countries
China
Contacts
Public ContactYi Liu
West China Hospital, Sichuan University
Outcome results
None listed